Notes

Direct Versus Iterated Multi-Step Forecasting of Glycaemia within Variety One particular Diabetes patients Making use of Autoregressive Versions.
Effective and culturally appropriate hand-hygiene education is essential to promote health-related practices to control and prevent diseases such as Diarrhoea, Ebola and COVID-19. In this paper we outline and evaluate the Co-Creation processes underpinning a handwashing intervention for young children (A Germ's Journey) developed and delivered in India, Sierra Leone and the UK, and consider the implications surrounding Imperialist/Colonial discourse and the White Saviour Complex. The paper focuses both on the ways Co-Creation was conceptualised by our collaborators in all three countries and the catalysts and challenges encountered. Qualitative data have been drawn from in-depth interviews with five key stakeholders, focus group data from 37 teachers in Sierra Leone and responses to open-ended questionnaires completed by teachers in India (N = 66) and UK (N = 63). Data were analysed using thematic analysis and three themes, each with three constituent subthemes are presented. In the theme 'Representations of the ethical and participatory values of Co-Creation with pragmatic considerations about ensuring an effective final 'product'.Open research data practices are a relatively new, thus still evolving part of scientific work, and their usage varies strongly within different scientific domains. In the literature, the investigation of open research data practices covers the whole range of big empirical studies covering multiple scientific domains to smaller, in depth studies analysing a single field of research. Despite the richness of literature on this topic, there is still a lack of knowledge on the (open) research data awareness and practices in materials science and engineering. While most current studies focus only on some aspects of open research data practices, we aim for a comprehensive understanding of all practices with respect to the considered scientific domain. Hence this study aims at 1) drawing the whole picture of search, reuse and sharing of research data 2) while focusing on materials science and engineering. The chosen approach allows to explore the connections between different aspects of open research data practices,he time needed for a precise description of the data and their generation process is named as biggest obstacle for data sharing. From these findings, a precise set of actions is derived suitable to support Open Data, involving training for researchers and introducing rewards for data sharing on the level of universities and funding bodies.Endocrine profiling is an increasingly utilized tool for detecting pregnancies in wild populations of mammals. Given the difficulty in calculating reproductive rates of Pacific walruses (Odobenus rosmarus divergens) the use of endocrine techniques for determining pregnancy rates could be particularly useful for management of the population. The goals of this study were to 1) determine if progesterone and total estrogen concentrations in ovarian tissues of female walruses could be used to determine reproductive state and 2) determine if walruses undergo a functional postpartum estrus, as is seen in other pinnipeds. Ovaries were collected from female walruses (n = 13) hunted in subsistence hunts by Alaska Native communities. Females were categorized as postpartum, full-term pregnant, pregnant diapause or unbred. Total estrogen concentrations were greatest in unbred (n = 2) and pregnant (n = 2) females. Progesterone concentrations were also nominally larger in unbred (n = 2) than pregnant (n = 2) and postpartum (n = 9) animals. Small samples sizes precluded the use of statistical comparisons among groups. Corpora lutea tissue samples in this study did not reflect the presence of a postpartum estrus in the month of May as postpartum females yielded lower total estrogen concentrations than unbred or pregnant animals. Both unbred animals were in a state of pseudopregnancy, which has not been physiologically described for this species before. The progesterone profiles in late (59 ng/g) and early (140 ng/g) pregnancy were lower than expected and fell within the range of the postpartum females (36-210 ng/g), suggesting low production of the hormone by the corpus luteum during these phases of pregnancy. Profiling reproductive hormones in free-ranging walruses demonstrates that an endocrine approach may be a valuable tool for determining reproductive status of females, however increased sample sizes and time of year must be considered to accurately separate pregnant versus pseudopregnant individuals.This study quantifies the economic effect of a possible lockdown of Tokyo to prevent the spread of COVID-19. The negative effect of such a lockdown may propagate to other regions through supply chains because of supply and demand shortages. Applying an agent-based model to the actual supply chains of nearly 1.6 million firms in Japan, we simulate what would happen to production activities outside Tokyo if production activities that are not essential to citizens' survival in Tokyo were shut down for a certain period. We find that if Tokyo were locked down for a month, the indirect effect on other regions would be twice as large as the direct effect on Tokyo, leading to a total production loss of 27 trillion yen in Japan or 5.2% of the country's annual GDP. Although the production that would be shut down in Tokyo accounts for 21% of the total production in Japan, the lockdown would result in an 86% reduction of the daily production in Japan after one month.Dandelion (Taraxacum officinale), a common plant worldwide, is used as both a medicine and food. Fermentation is a food processing technology that has many advantages, such as low energy cost, changes in product characteristics, and enhanced product quality. The purpose of this study was to investigate the effect of solid-state fermentation (SSF) on the content, composition and antioxidant activity of dandelion flavonoids. Response surface methodology was used to optimize dandelion fermentation conditions. Under optimized conditions, the maximum flavone concentration was 66.05 ± 1.89 mg/g. The flavonoid content of the crude extract from fermented dandelion (FDF) was 183.72 ± 2.24 mg/g. The flavonoid compounds in the crude extracts were further identified by UPLC-ESI-MS/MS. A total of 229 flavonoid compounds were identified, and 57 differential flavonoids (including 27 upregulated and 30 downregulated flavonoids) between FDF and the crude extract of unfermented dandelion (DF) were observed, of which 25 were annotated to metabolic pathways. FDF displayed superior antioxidant activity to that of DF in in vitro DPPH radical-scavenging and reducing power assays. The favorable results of our investigation could provide a new way for the exploitation and utilization of dandelion, which could be promising for its application as an antioxidant and functional food additive with flavonoids as ingredients.
The psychological health of female sex workers (FSWs) has emerged as a major public health concern in many low- and middle-income countries (LMICs). Key risk factors include poverty, low education, violence, alcohol and drug use, human immunodeficiency virus (HIV), and stigma and discrimination. This systematic review and meta-analysis aimed to quantify the prevalence of mental health problems among FSWs in LMICs, and to examine associations with common risk factors.

The review protocol was registered with PROSPERO, number CRD42016049179. We searched 6 electronic databases for peer-reviewed, quantitative studies from inception to 26 April 2020. Study quality was assessed with the Centre for Evidence-Based Management (CEBM) Critical Appraisal Tool. Pooled prevalence estimates were calculated for depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal behaviour. Meta-analyses examined associations between these disorders and violence, alcohol/drug use, condom use, and HIV/sexually transmittvulnerabilities and highlight the urgent need for interventions designed to improve the mental health and well-being of FSWs.Non-physician clinicians (NPCs) in low and middle-income countries (LMICs) often have little physical proximity to the resources-equipment, supplies or skills-needed to deliver effective care, forcing them to refer patients to distant sites. Unlike equipment or supplies, which require dedicated supply chains, physician/specialist skills needed to support NPCs can be sourced and delivered through telecommunication technologies. In LMICs however, these skills are scarce and sparsely distributed, making it difficult to implement commonly used real-time (synchronous), hub-and-spoke telemedicine paradigms. An asynchronous teleconsultations service was implemented in Turkana County, Kenya, connecting NPCs with a volunteer network of remote physicians and specialists. In 2017-18, the service supported over 100 teleconsultations and referrals across 20 primary healthcare clinics and two hospitals. This qualitative study aimed to explore the impact of the telemedicine intervention on health system stakeholders, and pe reveal the wider impact that modern teleconsultation services enabled by mobile technologies and algorithms can have on LMIC communities and health systems. The study highlights the importance of viewing provider-to-provider teleconsultations as complex health service delivery interventions with multiple pathways and processes that can ultimately improve health outcomes.
Although antiretroviral therapy (ART) significantly improves the survival status and quality of life among human immunodeficiency virus (HIV)-infected children, loss to follow-up (LTFU) from HIV-care profoundly affecting the treatment outcomes of this vulnerable population. For better interventions, up-to-date information concerning LTFU among HIV-infected children on ART is vital. However, only a few studies have been conducted in Ethiopia to address this concern. Thus, this study aims to identify the predictors of LTFU among HIV-infected children receiving ART at Debre Markos Referral Hospital.

An institution-based retrospective follow-up study was done among 408 HIV-infected children receiving ART at Debre Markos Referral Hospital between 2005 and March 15, 2019. Data were abstracted from the medical records of HIV-infected children using a standardized data abstracted checklist. We used Epi-Data Version 3.1 for data entry and Stata Version 14 for statistical analysis. The Kaplan-Meier survival curve wherence, started ART based on test and treat approach, and taking PI-based ART regimens were at higher risk of LTFU.
This study found that one in every six HIV-infected children lost form ART follow-up. HIV-infected children living in rural areas, having fair or poor ART drug adherence, started ART based on test and treat approach, and taking PI-based ART regimens were at higher risk of LTFU.Holothuria leucospilota (Echinodermata Holothuroidea) is a widespread tropical sea cucumber with strong value for the ecological restoration of coral reefs. Therefore, some studies regarding the artificial breeding and cultivation of H. leucospilota have been undertaken recently. However, the biological functions of the digestive system of this species have not been elucidated. In this study, a cDNA coding for α-amylase, an indicator of digestive maturity in animals, was identified from H. leucospilota and designated Hl-Amy. The full-length cDNA of the Hl-Amy gene, which is 1734 bp in length with an open reading frame (ORF) of 1578 bp, encodes a 525 amino acid (a.a.) protein with a deduced molecular weight of 59.34 kDa. According to the CaZy database annotation, Hl-Amy belongs to the class of GH-H with the official nomenclature of α-amylase (EC 3.2.1.1) or 4-α-D-glucan glucanohydrolase. The Hl-Amy protein contains a signal peptide at the N-terminal followed by a functional amylase domain, which includes the cnowledge gap on the biological function and expression profiles of an essential digestive enzyme in sea cucumber, which may encourage future investigation toward rationalized diets for H. leucospilota in artificial cultivation, and optimized heterogenous prokaryotic systems for producing recombinant enzymes of marine origins.The prediction of exceptional or surprising growth in research is an issue with deep roots and few practical solutions. In this study, we develop and validate a novel approach to forecasting growth in highly specific research communities. Each research community is represented by a cluster of papers. Multiple indicators were tested, and a composite indicator was created that predicts which research communities will experience exceptional growth over the next three years. The accuracy of this predictor was tested using hundreds of thousands of community-level forecasts and was found to exceed the performance benchmarks established in Intelligence Advanced Research Projects Activity's (IARPA) Foresight Using Scientific Exposition (FUSE) program in six of nine major fields in science. Furthermore, 10 of 11 disciplines within the Computing Technologies field met the benchmarks. Specific detailed forecast examples are given and evaluated, and a critical evaluation of the forecasting approach is also provided.In this Perspective, David Mabey and colleagues discuss a recent PLOS Medicine article on azithromycin as an intervention for reducing child mortality.
Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α).

We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine.

Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine.

Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.
Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.
Although assessing nutrient intake through dietary surveys is desirable, it can be effort- and time-intensive. We aimed to develop a brief screening method for determining sodium intake in order to raise public awareness regarding the Dietary Reference Intakes for Japanese (DRI-J) 2020.

Using data from the 2015 National Health and Nutrition Survey, we compared dietary behaviours obtained from a self-administered questionnaire according to sodium intake, which was assessed from one-day dietary records by a semi-weighed method. Participants were divided into 4 groups based on the reference values of sodium (salt equivalent) shown in the DRI-J. We also randomly divided the participants into development and validation groups, and used logistic regression analysis to identify predictive factors for sex-specific DRI-J (<7.5 g/day in men and <6.5 g/day in women) and above-average intakes (≥10 g/day in men and women).

Among the 6,172 Japanese individuals aged ≥20 years old, participants with lower sodium intake were found to use nutrition labels and had a lower frequency of eating out than those with higher intakes (P for difference < .001). Our final model for predicting sodium intake included adjusted sex, age, dietary behaviours, and consumption of mainly processed foods. In the development group, areas under the receiver operating characteristics curves were 0.747 and 0.741 for adherence to sex-specific DRI-J and above-average intake, respectively. The corresponding values in the validation group were 0.734 and 0.730, respectively.

This method could easily identify sodium intake using dietary behaviours and specific food consumption, and is expected to be widely useful for health and nutrition education in Japan.
This method could easily identify sodium intake using dietary behaviours and specific food consumption, and is expected to be widely useful for health and nutrition education in Japan.
Biannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status.

A large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities hat clinicaltrials.gov NCT02047981.Calcium imaging with fluorescent protein sensors is widely used to record activity in neuronal populations. The transform between neural activity and calcium-related fluorescence involves nonlinearities and low-pass filtering, but the effects of the transformation on analyses of neural populations are not well understood. We compared neuronal spikes and fluorescence in matched neural populations in behaving mice. We report multiple discrepancies between analyses performed on the two types of data, including changes in single-neuron selectivity and population decoding. These were only partially resolved by spike inference algorithms applied to fluorescence. To model the relation between spiking and fluorescence we simultaneously recorded spikes and fluorescence from individual neurons. Using these recordings we developed a model transforming spike trains to synthetic-imaging data. The model recapitulated the differences in analyses. Our analysis highlights challenges in relating electrophysiology and imaging data, and suggests forward modeling as an effective way to understand differences between these data.
Hypertension, together with obesity, is a leading cause of mortality and disability. Whilst metabolic surgery offers remission of several metabolic comorbidities, the effect for patients with hypertension remains controversial. The objective of the present study was to evaluate the effect of metabolic surgery on cardiovascular events and mortality on patients with morbid obesity (body mass index [BMI] ≥ 35 kg/m2) and hypertension.

We conducted a matched cohort study of 11,863 patients with morbid obesity and pharmacologically treated hypertension operated on with metabolic surgery and a matched non-operated-on control group of 26,199 subjects with hypertension (matched by age, sex, and area of residence) of varied matching ratios from 11 to 19, using data from the Scandinavian Obesity Surgery Register (SOReg), the Swedish National Patient Registers (NPR) for in-hospital and outpatient care, the Swedish Prescribed Drug Register, and Statistics Sweden. The main outcome was major adverse cardiovascular eventpatients with morbid obesity and pharmacologically treated hypertension was associated with lower risk for MACEs and all-cause mortality compared with age- and sex-matched controls with hypertension from the general population.
Metabolic surgery on patients with morbid obesity and pharmacologically treated hypertension was associated with lower risk for MACEs and all-cause mortality compared with age- and sex-matched controls with hypertension from the general population.During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase.
Patients diagnosed with Oral Floor Squamous Cell Carcinoma (OFSCC) face considerable challenges in physiology and psychology. This study explored prognostic signatures to predict prognosis in OFSCC through a detailed transcriptomic analysis.

We built an interactive competing endogenous RNA (ceRNA) network that included lncRNAs, miRNAs and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the gene functions and regulatory pathways of mRNAs. Least absolute shrinkage and selection operator algorithm (LASSO) analysis and Cox regression analysis were used to screen prognosis factors. The Kaplan-Meier method was used to analyze the survival rate of prognosis factors. Risk score was used to assess the reliability of the prediction model.

A specific ceRNA network consisting of 56 mRNAs, 16 miRNAs and 31 lncRNAs was established. Three key genes (HOXC13, TGFBR3, KLHL40) and 4 clinical factors (age, gender, TNM, and clinical stage) were identified and effectively predicted the for survival time. The expression of a gene signature was validated in two external validation cohorts. The signature (areas under the curve of 3 and 5 years were 0.977 and 0.982, respectively) showed high prognostic accuracy in the complete TCGA cohort.

Our study successfully developed an extensive ceRNA network for OFSCC and further identified a 3-mRNA and 4-clinical-factor signature, which may serve as a biomarker.
Our study successfully developed an extensive ceRNA network for OFSCC and further identified a 3-mRNA and 4-clinical-factor signature, which may serve as a biomarker.New and facile one-pot three component approach for the synthesis of substituted dihydropyrimidinones derivatives (4a-4h) from reaction of equimolar substituted aldehydes (1a-1h), methyl acetoacetate (2a) and urea (3a) in presence of nature derived catalyst viz. Cocos nucifera L. juice, Solanum lycopersicum L. juice and Citrus limetta juice, commonly known as coconut juice, tomato juice and musambi juice respectively, at room temperature has been carried out. All synthesized compounds were evaluated for in vitro herbicidal activity against Raphanus sativus L. (Radish seeds). The compounds (4a-4h) were also screened for their antifungal activity against Rhizoctonia solani and Colletotrichum gloeosporioides by poisoned food techniques method. Antibacterial activity was also studied against Erwinia cartovora and Xanthomonas citri by inhibition zone method. From activity data, it was found that compounds 4g and 4d were most active against Raphanus sativus L. (root) and Raphanus sativus L. (shoot) respectively. Compounds 4f and 4c was found most active against Rhizoctonia solani and Colletotrichum gloeosporioides fungus respectively at highest concentration. Compound 4g has shown maximum inhibition zone i.e. 1.00-5.50 mm against Erwinia cartovora at 2000 μg/mL concentration. Maximum Xanthomonas citrii growth was inhibited by compounds 4f showing inhibition zone 4.00-12.00 mm at highest concentration. Short reaction time, high yields, mild reaction condition and simple work-up are some merits of present methodology.Patients who are incarcerated are a vulnerable patient population and may suffer from less access to routine cancer screenings compared to their non-incarcerated counterparts. Therefore, a thorough evaluation of potential differences in cancer diagnosis staging is needed. We sought to examine whether there are differences in cancer stage at initial diagnosis between non-incarcerated and incarcerated patients by pursuing a retrospective chart review from 2010-2017 for all patients who were newly diagnosed with cancer at an urban safety net hospital. Incarceration status was determined by insurance status. Our primary outcome was incarceration status at time of initial cancer diagnosis. Overall, patients who were incarcerated presented at a later cancer stage for all cancer types compared to the non-incarcerated (+.14 T stage, p = .033; +.23 N stage, p less then .001). Incarcerated patients were diagnosed at later stages for colorectal (+0.93 T stage, p less then .001; +.48 N stage, p less then .001), oropharyngeal (+0.37 N stage, p = .003), lung (+0.60 N stage, p = .018), skin (+0.59 N stage, p = 0.014), and screenable cancers (colorectal, prostate, lung) as a whole (+0.23 T stage, p = 0.002; +0.17 N stage, p = 0.008). Incarcerated patients may benefit from more structured screening protocols in order to improve the stage at presentation for certain malignancies.Plant NLR immune receptors are multidomain proteins that can function as specialized sensor/helper pairs. Paired NLR immune receptors are generally thought to function via negative regulation, where one NLR represses the activity of the second and detection of pathogen effectors relieves this repression to initiate immunity. However, whether this mechanism is common to all NLR pairs is not known. Here, we show that the rice NLR pair Pikp-1/Pikp-2, which confers resistance to strains of the blast pathogen Magnaporthe oryzae (syn. Pyricularia oryzae) expressing the AVR-PikD effector, functions via receptor cooperation, with effector-triggered activation requiring both NLRs to trigger the immune response. To investigate the mechanism of Pikp-1/Pikp-2 activation, we expressed truncated variants of these proteins, and made mutations in previously identified NLR sequence motifs. We found that any domain truncation, in either Pikp-1 or Pikp-2, prevented cell death in the presence of AVR-PikD, revealing that all domains are required for activity. Further, expression of individual Pikp-1 or Pikp-2 domains did not result in cell death. Mutations in the conserved P-loop and MHD sequence motifs in both Pikp-1 and Pikp-2 prevented cell death activation, demonstrating that these motifs are required for the function of the two partner NLRs. Finally, we showed that Pikp-1 and Pikp-2 associate to form homo- and hetero-complexes in planta in the absence of AVR-PikD; on co-expression the effector binds to Pikp-1 generating a tri-partite complex. Taken together, we provide evidence that Pikp-1 and Pikp-2 form a fine-tuned system that is activated by AVR-PikD via receptor cooperation rather than negative regulation.
To preliminary assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models.

NOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptor's status was carried out after the MR images acquisition by immunohistochemistry on excised tumours.

Manganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (p<0.01), whereas TRPV6 expression levels appeared not relevant to the Mn uptake.

Our preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors.
Our preliminary results suggest that MEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of calcium receptors.Olfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adult mice, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that centrioles are amplified in immediate neuronal precursors (INPs) concomitant with elevation of mRNA for polo-like kinase 4 (Plk4) and SCL/Tal1-interrupting locus gene (Stil), key regulators of centriole duplication. These results support a model in which centriole amplification occurs during a transient state characterized by elevated Plk4 and Stil in early INP cells. These cells then go on to divide at least once to become OSNs, demonstrating that cell division with amplified centrioles, known to be tolerated in disease states, can occur as part of a normal developmental program.BACKGROUND Diabetic nephropathy (DN), the formation of albuminuria, is one of the most important complications seen in diabetic patients. IL-37, an inhibitor of congenital inflammation and immune response, plays an important role in the occurrence and development of diabetes, but its study in DN has not been previously reported. MATERIAL AND METHODS Podocyte transfection techniques were used to overexpress STAT3 and cyclophilin A (CypA). The expression of IL-37, STAT3, and CypA was detected by RT-qPCR and western blot. Cell survival was detected by CCK-8. The expression of inflammatory factors and molecules related to oxidative stress was detected by ELISA and western blot, and cell apoptosis was detected by flow cytometry and western blot. RESULTS The expression of IL-37 was significantly decreased in high glucose-treated podocytes. IL-37 improved the survival rate of podocytes suffering from high glucose-induced apoptosis. It inhibited the expression of the inflammation-related factors tumor necrosis factorpregulation of the STAT3-CypA signaling pathway can inhibit the protective effect of IL-37 against podocyte injury induced by high glucose.BACKGROUND Spontaneous intracranial hypotension (SIH) is a rare cause of postural headache. In most patients, the site of cerebrospinal fluid (CSF) leak is at the cervical or thoracic spinal level. The imaging modalities to establish the diagnosis of SIH include computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, CT, and MRI myelography, and radionuclide cisternography. Treatment usually consists of conservative measures, but patients unresponsive to these treatments can be treated by epidural blood patch (EBP) administration at the site of CSF leak. CASE REPORT A 25-year-old-man presented with headache aggravated upon sitting or standing and relieved by lying supine or consuming coffee. There was no history of recent trauma, lumbar puncture, or spinal anesthesia. His neurological examination was unremarkable. MRI of his head and entire spine showed features of intracranial hypotension with no obvious CSF leak. He was treated conservatively but his symptoms persisted. CT spinal myelography showed significant leakage of contrast medium at the retrospinal region between C1 and C2 spinous processes. The patient underwent cervical EBP administration under fluoroscopic guidance. His symptoms resolved completely and he remains asymptomatic more than 6 months later. CONCLUSIONS SIH is an important cause of postural headache. In patients with non-resolving symptoms, further investigations are warranted to identify potential CSF leak. Patients found to have a CSF leak at the level of the cervical spine can be safely and effectively treated by cervical EBP administration.Dilated cardiomyopathy (DCM) is often associated with sarcomere protein mutations that confer reduced myofilament tension-generating capacity. We demonstrated that cardiac twitch tension-time integrals can be targeted and tuned to prevent DCM remodeling in hearts with contractile dysfunction. We employed a transgenic murine model of DCM caused by the D230N-tropomyosin (Tm) mutation and designed a sarcomere-based intervention specifically targeting the twitch tension-time integral of D230N-Tm hearts using multiscale computational models of intramolecular and intermolecular interactions in the thin filament and cell-level contractile simulations. Our models predicted that increasing the calcium sensitivity of thin filament activation using the cardiac troponin C (cTnC) variant L48Q can sufficiently augment twitch tension-time integrals of D230N-Tm hearts. Indeed, cardiac muscle isolated from double-transgenic hearts expressing D230N-Tm and L48Q cTnC had increased calcium sensitivity of tension development and increased twitch tension-time integrals compared with preparations from hearts with D230N-Tm alone. Longitudinal echocardiographic measurements revealed that DTG hearts retained normal cardiac morphology and function, whereas D230N-Tm hearts developed progressive DCM. We present a computational and experimental framework for targeting molecular mechanisms governing the twitch tension of cardiomyopathic hearts to counteract putative mechanical drivers of adverse remodeling and open possibilities for tension-based treatments of genetic cardiomyopathies.Therapeutic strategies designed to target TP53-deficient cancer cells remain elusive. Here, we showed that TP53 loss initiated a pharmacologically actionable secretory process that drove lung adenocarcinoma (LUAD) progression. Molecular, biochemical, and cell biological studies showed that TP53 loss increased the expression of Golgi reassembly and stacking protein 55 kDa (G55), a Golgi stacking protein that maintains Golgi organelle integrity and is part of a GOLGIN45 (G45)-myosin IIA-containing protein complex that activates secretory vesicle biogenesis in the Golgi. TP53 loss activated G55-dependent secretion by relieving G55 and myosin IIA from miR-34a-dependent silencing. G55-dependent secreted proteins enhanced the proliferative and invasive activities of TP53-deficient LUAD cells and promoted angiogenesis and CD8+ T cell exhaustion in the tumor microenvironment. A small molecule that blocks G55-G45 interactions impaired secretion and reduced TP53-deficient LUAD growth and metastasis. These results identified a targetable secretory vulnerability in TP53-deficient LUAD cells.CD4+ T cell interactions with B cells play a critical role in the pathogenesis of systemic autoimmune diseases such as systemic lupus and chronic graft-versus-host disease (cGVHD). Extrafollicular CD44hiCD62LloPSGL1loCD4+ T cells (PSGL1loCD4+ T cells) are associated with the pathogenesis of lupus and cGVHD, but their causal role has not been established. With murine and humanized MHC-/-HLA-A2+DR4+ murine models of cGVHD, we showed that murine and human PSGL1loCD4+ T cells from GVHD target tissues have features of B cell helpers with upregulated expression of programmed cell death protein 1 (PD1) and inducible T cell costimulator (ICOS) and production of IL-21. They reside in nonlymphoid tissues without circulating in the blood and have features of tissue-resident memory T cells with upregulated expression of CD69. Murine PSGL1loCD4+ T cells from GVHD target tissues augmented B cell differentiation into plasma cells and production of autoantibodies via their PD1 interaction with PD-L2 on B cells. Human PSGL1loCD4+ T cells were apposed with memory B cells in the liver tissues of humanized mice and cGVHD patients. Human PSGL1loCD4+ T cells from humanized GVHD target tissues also augmented autologous memory B cell differentiation into plasma cells and antibody production in a PD1/PD-L2-dependent manner. Further preclinical studies targeting tissue-resident T cells to treat antibody-mediated features of autoimmune diseases are warranted.BACKGROUNDThe ABO histo-blood group is defined by carbohydrate modifications and is associated with risk for multiple diseases, including acute respiratory distress syndrome (ARDS). We hypothesized that genetically determined blood subtype A1 is associated with increased risk of ARDS and markers of microvascular dysfunction and coagulation.METHODSWe conducted analyses in 3 cohorts of critically ill trauma and sepsis patients (n = 3710) genotyped on genome-wide platforms to determine the association of the A1 blood type genotype with ARDS risk. We subsequently determined whether associations were present in FUT2-defined nonsecretors who lack ABO antigens on epithelium, but not endothelium. In a patient subgroup, we determined the associations of blood type with plasma levels of endothelial glycoproteins and disseminated intravascular coagulation (DIC). Lastly, we tested whether blood type A was associated with less donor lung injury recovery during human ex vivo lung perfusion (EVLP).RESULTSThe A1 genotype was associated with a higher risk of moderate to severe ARDS relative to type O in all 3 populations. In sepsis, this relationship was strongest in nonpulmonary infections. The association persisted in nonsecretors, suggesting a vascular mechanism. The A1 genotype was also associated with higher DIC risk as well as concentrations of thrombomodulin and von Willebrand factor, which in turn were associated with ARDS risk. Blood type A was also associated with less lung injury recovery during EVLP.CONCLUSIONWe identified a replicable association between ABO blood type A1 and risk of ARDS among the critically ill, possibly mediated through microvascular dysfunction and coagulation.FUNDINGNIH HL122075, HL125723, HL137006, HL137915, DK097307, HL115354, HL101779, and the University of Pennsylvania McCabe Fund Fellowship Award.A critical response to lysosomal membrane permeabilization (LMP) is the clearance of damaged lysosomes through a selective form of macroautophagy known as lysophagy. Although regulators of this process are emerging, whether organ- and cell-specific components contribute to the control of lysophagy remains incompletely understood. Here, we examined LMP and lysophagy in Niemann-Pick type C (NPC) disease, an autosomal recessive disorder characterized by the accumulation of unesterified cholesterol within late endosomes and lysosomes, leading to neurodegeneration and early death. We demonstrated that NPC human fibroblasts show enhanced sensitivity to lysosomal damage as a consequence of lipid storage. Moreover, we described a role for the glycan-binding F-box protein 2 (Fbxo2) in CNS lysophagy. Fbxo2 functions as a component of the S phase kinase-associated protein 1-cullin 1-F-box protein (SKP1-CUL1-SCF) ubiquitin ligase complex. Loss of Fbxo2 in mouse primary cortical cultures delayed clearance of damaged lysosomes and decreased viability after lysosomal damage. Moreover, Fbxo2 deficiency in a mouse model of NPC exacerbated deficits in motor function, enhanced neurodegeneration, and reduced survival. Collectively, our data identified a role for Fbxo2 in CNS lysophagy and establish its functional importance in NPC.Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4-/-) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling, and electrophysiological characterization, we detected TRPV4 in bronchial epithelium, alveolar epithelial type I (ATI), and alveolar epithelial type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of the water-conducting aquaporin-5 (AQP-5) channel in ATI cells. Migration of TRPV4-/- ATI cells was reduced, and cell barrier function was impaired. Analysis of isolated primary TRPV4-/- ATII cells revealed a reduced expression of surfactant protein C, and the TRPV4 activator GSK1016790A induced increases in current densities only in WT ATII cells. Moreover, TRPV4-/- lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared with WT lungs. Therefore, our data illustrate essential functions of TRPV4 channels in alveolar epithelial cells and in protection from edema formation.Impaired tolerance to innocuous particles during allergic asthma has been linked to increased plasticity of FoxP3+ regulatory T cells (Tregs) reprogramming into pathogenic effector cells, thus exacerbating airway disease. However, failure of tolerance mechanisms is driven by Th2 inflammatory signals. Therefore, the in vivo role of canonical IL-4 receptor α (IL-4Rα) signaling, an essential driver of Th2-type airway responses to allergens, on the regulatory function of FoxP3+ Tregs in allergic asthma was explored. Here, we used transgenic Foxp3cre IL-4Rα-/lox and littermate control mice to investigate the role of IL-4 and IL-13 signaling via Tregs in house dust mite-induced (HDM-induced) allergic airway disease. We sensitized mice intratracheally on day 0, challenged them on days 6-10, and analyzed airway hyperresponsiveness (AHR), airway inflammation, mucus production, and cellular profile on day 14. In the absence of IL-4Rα responsiveness on FoxP3+ Tregs, exacerbated AHR and airway inflammation were shown in HDM-sensitized mice. Interestingly, reduced induction of FoxP3+ Tregs accompanied increased IL-33 alarmin production and type 2 innate lymphoid cell activation in the lung, exacerbating airway hyperreactivity and lung eosinophilia. Taken together, our findings indicate that IL-4Rα-unresponsive FoxP3+ Tregs result in exaggerated innate Th2-type, IL-33-dependent airway inflammation and a break in tolerance during allergic asthma.Due to its high capacity (1675 mAh g-1), Li-S batteries have been considered as one of the ideal energy storage systems. The grand challenges of lithium-sulfur batteries are sulfur immobilization and improving electrical conductivity of cathode composite. The carbon-sulfur (C-S) composites and the polar materials (Ni(OH)2, TiO2, MnO2, TiS2, Co9S8, etc) integration have been proven to be two of the most effective routes to achieving good Li-S battery performance. However, each strategy has drawbacks the C-S composites have low volume density and the polar materials are often lack of electrical conductivity. Therefore, the hybridization of carbon and polar materials shall provide synergistic effects achieving ideal sulfur cathode. Herein, a hybrid material with carbon-coated NiS nanoparticles grown on graphene sheets was synthesized through a hydrothermal reaction followed by two steps of annealing. The obtained composite has a well-balanced ratio between graphene and NiS. An optimized energy density was demonstrated in lithium-sulfur cells.The photoconductive detector based on a graphene-silicon heterostructure retains excellent optoelectrical properties, in which the graphene plays an indispensable role, acting as the carrier transporting channel. Herein, we systematically investigate by simulation and experiment how doping graphene will affect the performance of graphene-silicon hybrid photoconductors. Compared with lightly p-doped graphene devices, the responsivity can be made nine times better through increasing the p-type doping level. In addition, the net photocurrent can also be enhanced by about four times through increasing the n-type doping level of graphene. We attribute this improvement to the barrier height change adjusted by doping graphene, which can optimize the lifetime and transport of photocarriers. Such a graphene-doping method, that manipulates the junction region, could offer useful guidance for achieving high-performance graphene photodetectors.Semiconductor quantum dots (QDs) in the InAs/AlGaAs system are of great importance due to their promising optoelectronic and nanophotonic applications. However, control over emission wavelength governed by Al content in the matrix is still limited because of an influence of surface Al content on QD size and density. In this paper, we study the growth of In nanostructures by droplet epitaxy on various AlGaAs surfaces. We demonstrate that an increase in the Al content leads to a decrease in the droplet density and an increase in their size, which contradicts the Stranski-Krastanov QD growth. Using a hybrid analytical-Monte Carlo model, we explain this phenomenon by the fact that In adatoms acquire higher mobility on a first indium monolayer which is bound to surface Al atoms. This assumption is confirmed by the fact that a temperature decrease does not lead to a great increase in the critical thickness of droplet formation on the Al-containing surfaces whereas it changes considerably on the GaAs surface. Furthermore, the Al content influence on the formation of In droplets is much less significant than on the growth of InAs QDs by the Stranski-Krastanov mode. This gives an opportunity to use droplet epitaxy to control the matrix bandgap without considerable influence on the QD characteristics.A series of nanoparticles (NPs) with different Au content was successfully encapsulated into metal organic framework ZIF-8 with highly porous structure through room-temperature crystallization. X-ray diffraction, Fourier transform infrared spectroscopy, N2 adsorption and transmission electron microscopy were carried out to characterize the obtained Au@ZIF-8 heterogeneous catalytic material comprehensively. Au NPs were dispersed uniformly in the ZIF-8 and the Au NP diameter was 5-6 nm. The crystal structure of ZIF-8 was unchanged when compared with that before Au loading. It was found that the Au content plays an important role in the hydrogenation reaction. The obtained Au@ZIF-8 exhibited high hydrogenation activity to nitrophenol and excellent selectivity to aminophenol. The recyclability of the Au@ZIF-8 catalysts showed excellent catalytic performance and great stability in the recycling reaction.We apply the non-equilibrium molecular dynamics approach (NEMD) to study thermal rectification in a hybrid graphene-carbon nitride system ([Formula see text]) under a series of positive and negative temperature gradients. In this study, the effects of temperature difference, between two baths (ΔT), and sample size on thermal rectification are investigated. Our simulation results indicate positive correlation between thermal rectification and temperature difference for ΔT > 60 K, and high thermal rectification values, up to around 50% for ΔT = 100 K. Furthermore, this behavior remains practically consistent among different sample lengths. The underlying mechanism leading to a preferable direction for phonons is calculated using phonon density of states (DOS) on both sides of the [Formula see text] interface, and the contributions of in-plane and out-of-plane phonon modes in total thermal rectification are also explored.1D ZnO nanostructures have been widely explored due to their potential applications in ultraviolet (UV) region photodetectors because of their unique structural and optoelectronic properties. However, a large number of surface defect states leading to a noticeable dark current hinders their practical applications in UV photodetection. In this work, we have shown improved ZnO/Al2O3 core-shell microrod photodetectors, whose performance is significantly enhanced by defect passivation and the introduction of trap states by atomic layer deposition grown thin amorphous Al2O3 shell layer, as evidenced by steady-state and transient photoluminescence investigations. The photodetectors demonstrated suppressed dark current and increased photocurrent after capping the Al2O3 layer. Specifically, the ZnO/Al2O3 core-shell microrod photodetector exhibited a photoresponsivity as high as 0.019 A/(W cm-2) with the dark current as low as ∼1 × 10-11 A, and a high I light/I dark ratio of ∼104 under relatively weak light illumination (∼10 μW cm-2). The results presented in this work provide valuable pathways to boost the performance of 1D ZnO microrod-based photodetectors for future practical applications.Motivated by interesting physical and chemical properties created by doping and topological quantum state, we perform the density functional theory and the Boltzmann transport equation to systematically investigate the geometric structures, stabilities, electronic structures, thermal conductivities and thermoelectric properties for Sb and its oxidations (Sb2O and SbO). The predicted lattice thermal conductivity (k L ) of Sb is 11.6 nW K-1 at 300 K, but it would fall drastically when introducing O atoms. This is mainly attributed to the strong anharmonic interactions by adding O atoms, and few contributions are from the decreasing phonon group velocities caused by the compressed phonon spectrum. SbO has been proven as a topological insulator with a relatively large topological band gap (E g ) ∼ 0.156 eV, and meanwhile its carrier mobilities (345.78 cm2/Vs for electrons) and scattering time (44.27 × 10-14 s for electrons) are also rather high among all 2D materials, exhibiting the excellent thermoelectric performance.
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