Notes

Quantitative trait loci (QTL) analysis involving leaf associated features throughout spinach (Spinacia oleracea D.).
Cross-Sectional Study amid Common Inhabitants With regards to Expertise along with Frame of mind in the direction of Antibiotic Use within Traditional western Saudi Arabic.
Opportunities to boost cardiovascular health within the brand new U . s . office.
Suppressing TAM-derived exosomal miR-193a-5p successfully inhibited tumor progression and metastasis. Overall, miR-193a-5p from TAM-derived exosomes downregulates the TIMP2 gene to facilitate the development of RCC, which provides a novel perspective for developing therapeutic strategies for RCC.There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for several brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced microbiome changes which have been implicated in these effects, and some of which are shared between different brain disorders. While the majority of these findings have been demonstrated in preclinical and in cross-sectional, epidemiological studies, to date there is insufficient evidence from mechanistic human studies to make conclusions about causality between a specific diet and microbially mediated brain function. Many of the dietary benefits on microbiome and brain health have been attributed to anti-inflammatory effects mediated by the microbial metabolites of dietary fiber and polyphenols. The new attention given to dietary factors in brain disorders has the potential to improve treatment outcomes with currently available pharmacological and non-pharmacological therapies.Graphene is an attractive material for all-optical modulation because of its ultrafast optical response and broad spectral coverage. However, all-optical graphene modulators reported so far require high pump fluence due to the ultrashort photo-carrier lifetime and limited absorption in graphene. We present modulator designs based on graphene-metal hybrid plasmonic metasurfaces with highly enhanced light-graphene interaction in the nanoscale hot spots at pump and probe (signal) wavelengths. Based on this design concept, we have demonstrated high-speed all-optical modulators at near and mid-infrared wavelengths (1.56 μm and above 6 μm) with significantly reduced pump fluence (1-2 orders of magnitude) and enhanced optical modulation. Ultrafast near-infrared pump-probe measurement results suggest that the modulators' response times are ultimately determined by graphene's ultrafast photocarrier relaxation times on the picosecond scale. The proposed designs hold the promise to address the challenges in the realization of ultrafast all-optical modulators for mid-and far-infrared wavelengths.
Rodent and human β-cells are differentially susceptible to the "lipotoxic" effects of long-chain saturated fatty acids (LC-SFA) but the factors accounting for this are unclear. Here, we have studied the intracellular disposition of the LC-SFA palmitate in human vs rodent β-cells and present data that reveal new insights into the factors regulating β-cell lipotoxicity.

The subcellular distribution of the LC-SFA palmitate was studied in rodent (INS-1E and INS-1 823/13 cells) and human (EndoC-βH1) β-cells using confocal fluorescence and electron microscopy (EM). Protein expression was assessed by Western blotting and cell viability, by vital dye staining.

Exposure of INS-1 cells to palmitate for 24 h led to loss of viability, whereas EndoC-βH1 cells remained viable even after 72 h of treatment with a high concentration (1 mM) of palmitate. Use of the fluorescent palmitate analogue BODIPY FL C
revealed an early localisation of the LC-SFA to the Golgi apparatus in INS-1 cells and this correlated with disten the Golgi apparatus at early time points whereas, in EndoC- βH1 cells, it is routed preferentially into lipid droplets. This may account for the differential sensitivity of rodent vs human β-cells to "lipotoxicity" since manoeuvres leading to the incorporation of palmitate into lipid droplets is associated with the maintenance of cell viability in both cell types.
Cross-sectional explorative observational study.

Sexual satisfaction in people with spinal cord injury and their partners an explorative study.

To investigate the determinants of sexual satisfaction among individuals with spinal cord injury and relative partners by assuming a bio-psycho-social perspective.

Online survey.

Thirty-eight individuals (22 individuals with SCI and their partners) were provided with an anonymous self-report questionnaire. Bio-psycho-social dimensions were investigated by using the Barthel Modified Index, Beck Depression Inventory-II, Short Form Health Survey (SF-36). Sexual attitudes of participants were assessed via the Multidimensional Sexual Self-Concept Questionnaire (Snell, 1993).

While no differences were observed between individuals with SCI and their partners, women with SCI were overall more satisfied about their sexual life when compared to men with SCI. Coping strategies promoting self-efficacy and an active role in the sexual issues were predictive of Sexual Satisfaction in the couples of persons with SCI and their partners. No significant contribution was played by physical variables.

A tailored-made approach assessing the needs of both individuals with SCI and partners is a key aspect for effective sexual rehabilitation protocols. According to the needs and features of each couple, health professionals should drive individuals with SCI and partners to cope with their sexuality within a bio-psycho-social framework underlying it.
A tailored-made approach assessing the needs of both individuals with SCI and partners is a key aspect for effective sexual rehabilitation protocols. According to the needs and features of each couple, health professionals should drive individuals with SCI and partners to cope with their sexuality within a bio-psycho-social framework underlying it.Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive malignant cancer caused by a chromosomal translocation t(11;22)(p13;q12) that produces an oncogenic transcription factor, EWSR1-WT1. EWSR1-WT1 is essential for the initiation and progression of DSRCT. However, the precise mechanism by which EWSR1-WT1 drives DSRCT oncogenesis remains unresolved. Through our integrative gene expression analysis, we identified Salt Inducible Kinase 1 (SIK1) as a direct target of EWSR1-WT1. SIK1 as a member of the AMPK related kinase is involved in many biological processes. We showed that depletion of SIK1 causes inhibition of tumor cell growth, similar to the growth inhibition observed when EWSR1-WT1 is depleted. We further showed that silencing SIK1 leads to cessation of DNA replication in DSRCT cells and inhibition of tumor growth in vivo. Lastly, combined inhibition of SIK1 and CHEK1with small molecule inhibitors, YKL-05-099 and prexasertib, respectively, showed enhanced cytotoxicity in DSRCT cells compared to inhibition of either kinases alone. This work identified SIK1 as a new potential therapeutic target in DSRCT and the efficacy of SIK1 inhibition may be improved when combined with other intervention strategies.
The onset of delirium after major surgery is associated with worse in-hospital outcomes for major surgical patients. Best practice recommends assessing surgical patients for delirium risk factors and this includes screening for cognitive impairment. The Mini-Cog© is a short instrument which has been shown to predict postoperative delirium (POD) and other complications in elderly patients undergoing major elective surgery. The primary aim of this study was to ascertain whether a positive preoperative Mini-Cog© is associated with postoperative delirium in elective colorectal surgery patients at high-risk of mortality due to age or comorbidity. Secondary outcomes were 90-day mortality and length of stay.

This is a retrospective analysis of data gathered prospectively between October 2015 and December 2017. Baseline data were collected at a preoperative screening clinic, and postoperative data during daily ward rounds by the Perioperative Medicine team at The York Hospital.

Three hundred nineteen patients w.

Mini-Cog© is not independently associated with post-operative delirium in high-risk elective colorectal surgery patients in this cohort. Mini-Cog© shows promise as a possible predictor of 90-day mortality. Larger studies exploring preoperative cognitive status and postoperative confusion and mortality could improve risk-stratification for surgery and allocation of resources to those patients at higher risk.
Mini-Cog© is not independently associated with post-operative delirium in high-risk elective colorectal surgery patients in this cohort. Mini-Cog© shows promise as a possible predictor of 90-day mortality. Larger studies exploring preoperative cognitive status and postoperative confusion and mortality could improve risk-stratification for surgery and allocation of resources to those patients at higher risk.
Many studies still dispute the identification of independent risk factors that influence outcome after neonatal cardiac surgery. We present our study to announce the contemporary outcomes and risk profile of neonatal cardiac surgery at our institute.

We designed a retrospective study of neonatal patients who underwent surgery for congenital heart diseases between June 2011 and April 2020. Demographic, operative, and postoperative data were collected from medical records and surgical databases. The primary outcome was the operative mortality (in-hospital death) and secondary outcomes included hospital length of stay, intensive care unit stay, duration of mechanical ventilation.

In total, 1155 cardiac surgeries in children were identified; of these, 136 (11.8%) were performed in neonates. Arterial switch operations (48 cases) were the most frequent procedures. Postoperatively, 11 (8.1%) patients required extracorporeal membrane oxygenation, and 4 (2.9%) patients had complete heart block. Postoperative in-hospital mortality was 11%. The median postoperative duration of mechanical ventilation, intensive care unit stay, and hospital length of stay were 6, 18, and 24days, respectively.

The early outcomes of neonatal cardiac surgery are encouraging. The requirement of postoperative extracorporeal membrane oxygenation support, postoperative intracranial hemorrhage, and acute kidney were identified as independent risk factors of mortality following surgery for congenital heart defects in neonates.
The early outcomes of neonatal cardiac surgery are encouraging. The requirement of postoperative extracorporeal membrane oxygenation support, postoperative intracranial hemorrhage, and acute kidney were identified as independent risk factors of mortality following surgery for congenital heart defects in neonates.
We aim to study the clinical effect of moxibustion at Laogong interval with Panax notoginseng on the short-term maturation and long-term patency of arteriovenous fistula.

Seventy-four pre-dialysis uremic patients who received distal forearm radial-cephalic fistula creations were enrolled in this study and randomly assigned to the control group and experimental group. After arteriovenous fistula creations, the control group underwent handgrip exercise, and the experimental group received moxibustion at Laogong acupoint interval with Panax notoginseng. Both groups received a 12-week treatment and were followed up for 24weeks in all at the following time points before creations and 2, 4, 8, 12, 24weeks after creations. The diameter of anastomosis, the diameter and outflow of draining-veins 5cm above anastomosis, the diameter and outflow of brachial arteries evaluated the maturation and patency of arteriovenous fistula. Enzyme linked immunosorbent assay determined serum levels of endothelin and nitric oxide.
e control group at 2weeks after creations.

Moxibustion at Laogong interval with Panax notoginseng was non-invasive and promoted the maturation of arteriovenous fistula at 4weeks after creations. However, its long-term beneficial effect on patency at 24weeks after creations was not significant. Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024042. Registered, http//www.chictr.org.cn/index.aspx.
Moxibustion at Laogong interval with Panax notoginseng was non-invasive and promoted the maturation of arteriovenous fistula at 4 weeks after creations. However, its long-term beneficial effect on patency at 24 weeks after creations was not significant. Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024042. Registered, http//www.chictr.org.cn/index.aspx.
Alzheimer's disease is the most prevalent cause of dementia in the elderly. Neuronal death and synaptic dysfunctions are considered the main hallmarks of this disease. The latter could be directly associated to an impaired metabolism. In particular, glucose metabolism impairment has demonstrated to be a key regulatory element in the onset and progression of AD, which is why nowadays AD is considered the type 3 diabetes.

We provide a thread regarding the influence of glucose metabolism in AD from three different perspectives (i) as a regulator of the energy source, (ii) through several metabolic alterations, such as insulin resistance, that modify peripheral signaling pathways that influence activation of the immune system (e.g., insulin resistance, diabetes, etc.), and (iii) as modulators of various key post-translational modifications for protein aggregation, for example, influence on tau hyperphosphorylation and other important modifications, which determine its self-aggregating behavior and hence Alzheimer's pathogenesis.

In this revision, we observed a 3 edge-action in which glucose metabolism impairment is acting in the progression of AD as blockade of energy source (e.g., mitochondrial dysfunction), through metabolic dysregulation and post-translational modifications in key proteins, such as tau. Therefore, the latter would sustain the current hypothesis that AD is, in fact, the novel diabetes type 3.
In this revision, we observed a 3 edge-action in which glucose metabolism impairment is acting in the progression of AD as blockade of energy source (e.g., mitochondrial dysfunction), through metabolic dysregulation and post-translational modifications in key proteins, such as tau. Therefore, the latter would sustain the current hypothesis that AD is, in fact, the novel diabetes type 3.
Illegal logging is a global crisis with significant environmental, economic, and social consequences. Efforts to combat it call for forensic methods to determine species identity, provenance, and individual identification of wood specimens throughout the forest products supply chain. link= PhenolRedsodium DNA-based methodologies are the only tools with the potential to answer all three questions and the only ones that can be calibrated "non-destructively" by using leaves or other plant tissue and take advantage of publicly available DNA sequence databases. Despite the potential that DNA-based methods represent for wood forensics, low DNA yield from wood remains a limiting factor because, when compared to other plant tissues, wood has few living DNA-containing cells at functional maturity, it often has PCR-inhibiting extractives, and industrial processing of wood degrades DNA. To overcome these limitations, we developed a technique-organellar microcapture-to mechanically isolate intact nuclei and plastids from wood for subsequentlysis.
Organellar microcapture, while too labor-intensive for routine extraction of many specimens, successfully recovered intact nuclei from wood samples collected more than sixty-five years ago, plastids from fresh sapwood and leaves, and presents great potential for DNA extraction from recalcitrant plant samples such as tissues rich in secondary metabolites, old specimens (archaeological, herbarium, and xylarium specimens), or trace evidence previously considered too small for analysis.
To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and on treatment of elderly patients.

Medical records of 98 consecutive patients with squamous cell carcinoma of the anus of all stages treated with curative intent between 01-01-2009 and 31-12-2018 were analyzed with follow up until 31-12-2020. Standard tumor and pathological lymph node dose were 59.4Gy (median 59.4Gy, range 59.4-70Gy) or 60Gy (no deviation from intended dose), elective nodal regions were treated with 45Gy (no deviations). Radiotherapy techniques in this period evolved from 3D-conformal to IMRT and VMAT. In 23 patients electron beams were used.

Median age was 63years (range 41-88), the majority of patients were female (60%). Twenty three patients were > 75years old. The TNM stages were I, II, IIIA, and IIIB in 18%, 40%, 15% and 27%, 58% of patients had N0 status. Concurrent mitomycin C and 5-fluoruracil-based chemotherapy was given in 63 patients (64%). Five-year overall survival (OS), disease free survival (DFS), locoregional control (LRC) and colostomy free survival (CFS) were 71%, 80%, 82%, and 82% for the whole group. Results in patients > 75years of age were not statistically different from those in younger patients. With the introduction of more conformal techniques DFS did not change and toxicities decreased.

Real word treatment outcomes per disease stage were in line with what is reported in literature. Older patients should also be offered treatment with curative intent.
Real word treatment outcomes per disease stage were in line with what is reported in literature. Older patients should also be offered treatment with curative intent.
Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. PhenolRedsodium This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients.

Prospective data from breast cancer patients, treated with locoregional radiotherapy were collected between November 2015 and February 2020 in 3 comprehensive cancer centers. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used to compare HFRT and NFRT. Furthermore, risk factors of der better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.
The results of this study suggests that breast HFRT may be a better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.
A discoid medial meniscus is rare in comparison with a discoid lateral meniscus. We encountered a new type of incomplete discoid with an oversized posterior segment. Therefore, this study aimed to report cases of medial meniscus with an oversized posterior segment and analyze the morphological characteristics by comparing them to cases with a discoid medial meniscus and normal medial meniscus.

Four patients with an oversized posterior segment medial meniscus (oversize group, mean age 25.3 ± 12.0years) and seven patients with a discoid medial meniscus (discoid group, mean age 34.4 ± 19.6) were identified using magnetic resonance imaging (MRI) and diagnosed by arthroscopic findings in our hospital. Fifty patients without medial meniscal injury were retrospectively selected as the normal group (normal group, mean age 24.0 ± 11.3years). The clinical symptoms were examined. The anteroposterior (AP) length of both the anterior and posterior segments, AP length ratio of the posterior segment to the AP length of medial meniscus as a morphological abnormality.
Oversized posterior and normal anterior segments characterize this new type of incomplete discoid medial meniscus as a morphological abnormality.
To evaluate the impact of a nurse navigation program on treatment adherence and resolution of hepatitis C infection in patients with severe mental disorder.

An open, randomized, controlled trial with blinded outcome assessment. The intervention group will engage in a nurse navigation program designed by mental health nurses. The program involves active screening for patients with severe mental disorder. The patients and caregivers included in the program will receive information, training, support and guidance throughout the treatment and recovery process, which involves different healthcare professionals and units. The control group will receive the standard of care, which includes follow-up by a family physician, referral to the hepatologist, serological testing, new referral to the hepatologist, onset of treatment, and follow-up. Multidisciplinary care will be provided along a coordinated and seamless clinical pathway led by a nurse navigator. The primary endpoints are total recovery (hepatitis C cure) and treatment adherence. Occurrence of symptoms of schizophrenia and health-related quality of life will be also recorded. Follow-up of patients will be performed three and six months after the administration of antiviral treatment. The study was authorised by the Ethics Committee of Malaga in December 2021. Funding was approved in March 2021.

If this intervention is proven to be effective in improving treatment access and adherence, it will represent a step forward in addressing a chronic health issue that is 16 times more prevalent in the population with severe mental disease. Finally, this intervention may lead to the detection of undertreated HCV infection in this population of patients.

This protocol has been registered in ClinicalTrials.gov with identifier code NCT04891445 on May 18, 2021.
This protocol has been registered in ClinicalTrials.gov with identifier code NCT04891445 on May 18, 2021.
The global burden of cardiovascular disease and type 2 diabetes could be decreased by improving dietary factors, but identification of groups suitable for interventional approaches can be difficult. link2 Reporting of dietary intake is prone to errors, and measuring of metabolites has shown promise in determining habitual dietary intake. Our aim is to create a metabolic signature that is associated with healthy eating and test if it associates with type 2 diabetes and coronary artery disease risk.

Using plasma metabolite data consisting of 111 metabolites, partial least square (PLS) regression was used to identify a metabolic signature associated with a health conscious food pattern in the Malmö Offspring Study (MOS, n = 1538). The metabolic signature's association with dietary intake was validated in the Malmö Diet and Cancer study (MDC, n = 2521). The associations between the diet-associated metabolic signature and incident type 2 diabetes and coronary artery disease (CAD) were tested using Cox regression in o different cohorts. The association with diabetes was independent of traditional risk factors and might illustrate an effect of health conscious dietary intake on cardiometabolic health.
In this proof-of-concept study, we identified a healthy diet-associated metabolic signature, which was inversely associated with future risk for type 2 diabetes and coronary artery disease in two different cohorts. The association with diabetes was independent of traditional risk factors and might illustrate an effect of health conscious dietary intake on cardiometabolic health.Tyrosine kinase inhibitors (TKIs) such as imatinib (IM) are key drugs for treatment of chronic myeloid leukemia (CML). Development of drug resistance to TKIs due to BCR-ABL mutation, especially T315I mutation, poses a major challenge in the clinical treatment of CML. The purpose of this study was to test metabolic modulation as a potential strategy to overcome imatinib resistance based on the possible crosstalk between BCR-ABL signaling and metabolic changes in CML. 2-deoxy-d-glucose (2-DG) was used to modulate the glucose metabolism in CML cells sensitive to IM (KBM5 cell line) and resistant to imatinib with BCR-ABL T315I mutation (KBM5-T315I cell line). PhenolRedsodium Seahorse XFe24 extracellular flux analyzer to quantify oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) was used to measure cellular energy metabolism. Cell proliferation was analyzed by CCK-8 assay and MTS assay. Annexin V/PI staining was used to evaluate cell apoptosis. Autophagy-related proteins and enzyme/proteins were detected by Western blotting. Cellular ATP concentration was detected using an ATP-based Cell Titer Kit. link2 The combined action of 2-DG and IM was evaluated by calculating the drug combination index. Our results found that inhibition of glucose metabolism by 2-DG significantly impaired the viability of CML cells and co-treatment with 2-DG and imatinib induced a synergistic inhibition of KBM5 and KBM5-T315I cells. 2-DG induced cell death by autophagy, not by apoptosis, as evidenced by increased expression of Beclin1 and LC3AII and lack of annexin V/PI-positive cells. At the biochemical level, 2-DG inhibited glycolysis and mitochondrial oxygen consumption manifested by a significant decrease in ECAR and OCR, and a depletion of ATP. The severe metabolic stress induced by 2-DG in CML cells led to autophagic cell death. Our results suggested a metabolic vulnerability of CML cells that could be targeted by a combination of 2-DG and imatinib as an alternative treatment for imatinib-resistant CML.Pancreatic cancer (PC) is a growing global burden, remaining one of the most lethal cancers of the gastrointestinal tract. Moreover, PC is resistant to various treatments such as chemotherapy, radiotherapy, and immunotherapy. New therapies are urgently needed to improve the prognosis of PC. Oncolytic virus (OV) therapy is a promising new treatment option. OV is a genetically modified virus that selectively replicates in tumor cells. It can kill tumor cells without harming normal cells. The activation of tumor-specific T-cells is a unique feature of OV-mediated therapy. However, OV-mediated mono-therapeutic efficacy remains controversial, especially for metastatic or advanced patients who require systemically deliverable therapies. Hence, combination therapies will be critical to improve the therapeutic efficacy of OV-mediated therapy and prevent tumor recurrence. This review aims to investigate novel combinatorial treatments with OV therapy and explore the inner mechanism of those combined therapies, hopefully providing a new direction for a better prognosis of PC.
A significant subset of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric adenocarcinomas (GAC) are resistant to immune checkpoint inhibitors (ICIs), yet the underlying mechanism remains largely unknown. We sought to investigate the genomic correlates of the density of tumor-infiltrating immune cells (DTICs) and primary resistance to ICI treatment.

Four independent cohorts of MSI-H GAC were included (i) the surgery cohort (n = 175) with genomic and DTIC data, (ii) the 3DMed cohort (n = 32) with genomic and PD-L1 data, (iii) the Cancer Genome Atlas (TCGA) cohort (n = 73) with genomic, transcriptomic, and survival data, and (iv) the ICI treatment cohort (n = 36) with pre-treatment genomic profile and ICI efficacy data.

In the dMMR/MSI-H GAC, the number of mutated genes in the PI3K-AKT-mTOR pathway (NMP) was positively correlated with tumor mutational burden (P < 0.001) and sensitivity to PI3K-AKT-mTOR inhibitors and negatively correlated with CD3
(P < 0.001), CD4
( an immunotherapeutic adjuvant in NMP-high subpopulation to overcome the resistance to ICIs.Venetoclax plus cytarabine therapy is approved for elderly acute myeloid leukemia (AML) patients and needs further improvement. We studied the mechanisms of venetoclax plus cytarabine treatment and searched for a third agent to enhance their effects. Cytarabine induces S phase arrest-mediated DNA damage with activation of DNA replication checkpoint kinase 1 (Chk1) through phosphorylation, while venetoclax induces B cell lymphoma 2 (Bcl-2)-interacting mediator of cell death (Bim)-mediated apoptotic DNA damage. Myeloid cell leukemia-1 (Mcl-1) plays negative roles in both events by sequestering Bim and accelerating Chk1 phosphorylation. Venetoclax releases Bim from Bcl-2 with increased Bim binding to Mcl-1. Artesunate, an antimalaria drug, induces Noxa to replace Bim from Mcl-1 and induces synergistic apoptosis with venetoclax accompanied with Mcl-1 reduction. Silencing Mcl-1 or adding venetoclax/artesunate diminishes the cytarabine resistance pathway p-Chk1. The triple combination exhibits S phase arrest with enhanced DNA damage, improves AML colony formation inhibition, and prolongs survival of two mice xenograft models compared to the venetoclax/cytarabine dual combination. Artesunate serves as a bridge for venetoclax and cytarabine combination by Noxa and Bim-mediated apoptosis and Mcl-1 reduction. link3 We provide a new triple combination for AML treatment by targeting the Noxa/Mcl-1/Bim axis to reverse Mcl-1/p-Chk1 resistance of cytarabine therapy.
Variants in SLC34A2 encoding the sodium-dependent phosphate transport protein 2b (NaPi-IIb) cause the rare lung disease pulmonary alveolar microlithiasis (PAM). PAM is characterised by the deposition of calcium-phosphate concretions in the alveoli usually progressing over time. No effective treatment is available. So far, 30 allelic variants in patients have been reported but only a few have been functionally characterised. This study aimed to determine the impact of selected SLC34A2 variants on transporter expression and phosphate uptake in cellular studies.

Two nonsense variants (c.910A > T and c.1456C > T), one frameshift (c.1328delT), and one in-frame deletion (c.1402_1404delACC) previously reported in patients with PAM were selected for investigation. Wild-type and mutant c-Myc-tagged human NaPi-IIb constructs were expressed in Xenopus laevis oocytes. The transport function was investigated with a
Pi uptake assay. NaPi-IIb protein expression and localisation were determined with immunoblottinin the oocyte membrane. All mutant transporters were non-functional, supporting that dysfunction of NaPi-IIb underlies the pathology of PAM.
Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin.

A 62-year-old Hispanic female presented with a3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin.
F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (
TcO

) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, uppee thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.
Malaria is one of the major diseases affecting global health, while progress in malaria control and elimination has stagnated in some endemic countries. China has been certificated malaria free by World Health Organization in 2021, and will get more involved on global malaria elimination. Further discussion is needed on how to collaborate with the malaria endemic countries and provide effective help. This study was to investigate the perceptions of malaria endemic countries on China's contribution to global malaria elimination and to lay a foundation for further action.

Semi-structured interviews were conducted with key informants including national malaria project managers and technicians from malaria endemic countries. Thematic framework approach was used to analyze the data.

Malaria endemic countries now face challenges in insufficient funds, technique, products, public health systems and inadequacy of international assistance. They hold a positive attitude towards cooperation with China and identified experience and technique exchange, personnel training, system building and scientific research cooperation as prioritized areas.

China could make full use of its own advantages in technique transfer, health system improvement, information system construction, and health human resource training and take an active part in global malaria elimination.
China could make full use of its own advantages in technique transfer, health system improvement, information system construction, and health human resource training and take an active part in global malaria elimination.Integrative analysis of large-scale single-cell RNA sequencing (scRNA-seq) datasets can aggregate complementary biological information from different datasets. However, most existing methods fail to efficiently integrate multiple large-scale scRNA-seq datasets. We propose OCAT, One Cell At a Time, a machine learning method that sparsely encodes single-cell gene expression to integrate data from multiple sources without highly variable gene selection or explicit batch effect correction. We demonstrate that OCAT efficiently integrates multiple scRNA-seq datasets and achieves the state-of-the-art performance in cell type clustering, especially in challenging scenarios of non-overlapping cell types. In addition, OCAT can efficaciously facilitate a variety of downstream analyses.
Glassware can be an effective vehicle to recruit customers, revive brands, build profits and increase alcohol consumption by capitalising on the immediacy of glassware to the point of consumption. The design of glassware can also contribute to harm reduction by slowing and reducing consumption. Nucleated bases have been added to lager glasses in recent years which allow carbon dioxide (CO
) to be more rapidly released and ascend through the solution. The aim of these studies was to investigate the effect of nucleated glasses on the likeability and drinking rate of lager in alcohol drinkers.

In Study 1, participants (n = 116) were asked to taste two glasses of lager (280 millilitres (ml) each) in separate 5-min taste tests and fill out a likeability questionnaire after each glass in a within-subjects design with one factor of glass (nucleated, non-nucleated). The primary outcome was the likeability of lager and the secondary outcome was volume consumption during taste tests. In Study 2, participants (n = (volume consumed in Study 1 or drinking rate in Study 2) of lager, although they do seem to increase the visual appeal and refreshment of lager. This may increase the number of drinking episodes by making the drinking experience more enjoyable which may lead to increased alcohol related harm.
Nucleated lager glasses do not appear to alter the likeability or consumption (volume consumed in Study 1 or drinking rate in Study 2) of lager, although they do seem to increase the visual appeal and refreshment of lager. This may increase the number of drinking episodes by making the drinking experience more enjoyable which may lead to increased alcohol related harm.
Intestinal parasites and HIV/AIDS co-infection become a major public health concern in Africa. The management and care of HIV/AIDS patients is being complicated by intestinal parasitic infections. Therefore, this study aimed to determine the prevalence and associated factors of intestinal parasitic infections among people living with HIV at Dessie Referral Hospital, North-east Ethiopia.

This cross sectional study was conducted from March to May 2019. Systematic simple random sampling technique was used to recruit study participants. Stool specimen was collected and examined microscopically using wet mount, formol-ether concentration technique and modified Zeihl-Neelsen methods. Socio-demographic characteristics and associated factors were collected using structured questionnaire. The recent CD4 cell count was obtained from patients ART follow-up record. Data were analysed using SPSS version 20 software. Bivariate and multivariate logistic regression was done to investigate the association between independexamination and prompt treatment are necessary.
Robotic linac is ideally suited to deliver hypo-fractionated radiotherapy due to its compact head and flexible positioning. The non-coplanar treatment space improves the delivery versatility but the complexity also leads to prolonged optimization and treatment time.

In this study, we attempted to use the deep learning (pytorch) framework for the plan optimization of circular cone based robotic radiotherapy. The optimization problem was topologized into a simple feedforward neural network, thus the treatment plan optimization was transformed into network training. With this transformation, the pytorch toolkit with high-efficiency automatic differentiation (AD) for gradient calculation was used as the optimization solver. To improve the treatment efficiency, plans with fewer nodes and beams were sought. The least absolute shrinkage and selection operator (lasso) and the group lasso were employed to address the "sparsity" issue.

The AD-S (AD sparse) approach was validated on 6 brain and 6 liver cancer cases and the results were compared with the commercial MultiPlan (MLP) system. It was found that the AD-S plans achieved rapid dose fall-off and satisfactory sparing of organs at risk (OARs). Treatment efficiency was improved by the reduction in the number of nodes (28%) and beams (18%), and monitor unit (MU, 24%), respectively. The computational time was shortened to 47.3s on average.

In summary, this first attempt of applying deep learning framework to the robotic radiotherapy plan optimization is promising and has the potential to be used clinically.
In summary, this first attempt of applying deep learning framework to the robotic radiotherapy plan optimization is promising and has the potential to be used clinically.
This study aims to evaluate the discoloration rate of two types of composites, microhybrid and nanohybrid, after exposure to natural and commercially-produced juices.

In this experimental study, 90 disc-shaped specimens with a thickness of 2 mm and a diameter of 10 mm were taken from two composites, microhybrid P
(Kerr-ITALY) and nanohybrid Filtek Z250XT (3M-ESPE-USA) (two groups of 45). Then, the samples of each group were divided into five subgroups of nine and were immersed for 10 days for 4 h in five solutions of commercially-produced orange juice, natural orange juice, commercially-produced pomegranate juice, natural pomegranate juice, and distilled water (control group). The colour of the samples was measured by a reflective spectrophotometer using the CLEl*a*b colour space at baseline and after discoloration.

The independent t-test showed that the mean discoloration rate (∆E) of nanohybrid composite exposed to commercially-produced orange juice, natural pomegranate juice, and commercially-produmercially-produced pomegranate juice, is not recommended in the first few days after composite restoration.As a natural product with various biological activities, triptolide (TP) has been reported in anti-inflammatory, anti-tumor and anti-autoimmune studies. However, the narrow therapeutic window, poor water solubility, and fast metabolism limit its wide clinical application. To reduce its adverse effects and enhance its efficacy, research and design of targeted drug delivery systems (TDDS) based on nanomaterials is one of the most viable strategies at present. This review summarizes the reports and studies of TDDS combined with TP in recent years, including passive and active targeting of drug delivery systems, and specific delivery system strategies such as polymeric micelles, solid lipid nanoparticles, liposomes, and stimulus-responsive polymer nanoparticles. The reviewed literature presented herein indicates that TDDS is a multifunctional and efficient method for the delivery of TP. In addition, the advantages and disadvantages of TDDS are sorted out, aiming to provide reference for the combination of traditional Chinese medicine and advanced nano drug delivery systems (NDDS) in the future.Two-dimensional materials are attractive for constructing high-performance photonic chip-integrated photodetectors because of their remarkable electronic and optical properties and dangling-bond-free surfaces. However, the reported chip-integrated two-dimensional material photodetectors were mainly implemented with the configuration of metal-semiconductor-metal, suffering from high dark currents and low responsivities at high operation speed. Here, we report a van der Waals PN heterojunction photodetector, composed of p-type black phosphorous and n-type molybdenum telluride, integrated on a silicon nitride waveguide. The built-in electric field of the PN heterojunction significantly suppresses the dark current and improves the responsivity. Under a bias of 1 V pointing from n-type molybdenum telluride to p-type black phosphorous, the dark current is lower than 7 nA, which is more than two orders of magnitude lower than those reported in other waveguide-integrated black phosphorus photodetectors. An intrinsic responsivity up to 577 mA W-1 is obtained. Remarkably, the van der Waals PN heterojunction is tunable by the electrostatic doping to further engineer its rectification and improve the photodetection, enabling an increased responsivity of 709 mA W-1. Besides, the heterojunction photodetector exhibits a response bandwidth of ~1.0 GHz and a uniform photodetection over a wide spectral range, as experimentally measured from 1500 to 1630 nm. The demonstrated chip-integrated van der Waals PN heterojunction photodetector with low dark current, high responsivity and fast response has great potentials to develop high-performance on-chip photodetectors for various photonic integrated circuits based on silicon, lithium niobate, polymer, etc.
The application of virtual reality (VR) and robotic devices in neuromotor rehabilitation has provided promising evidence in terms of efficacy, so far. Usability evaluations of these technologies have been conducted extensively, but no overviews on this topic have been reported yet.

A systematic review of the studies on patients' and healthcare professionals' perspective through searching of PubMed, Medline, Scopus, Web of Science, CINAHL, and PsychINFO (2000 to 2021) was conducted. Descriptive data regarding the study design, participants, technological devices, interventions, and quantitative and qualitative usability evaluations were extracted and meta-synthetized.

Sixty-eight studies were included. VR devices were perceived as having good usability and as a tool promoting patients' engagement and motivation during the treatment, as well as providing strong potential for customized rehabilitation sessions. By contrast, they suffered from the effect of learnability and were judged as potentially requiring more mental effort. Robotics implementation received positive feedback along with high satisfaction and perceived safety throughout the treatment. Robot-assisted rehabilitation was considered useful as it supported increased treatment intensity and contributed to improved patients' physical independence and psychosocial well-being. Technical and design-related issues may limit the applicability making the treatment difficult and physically straining. Moreover, cognitive and communication deficits were remarked as potential barriers.

Overall, VR and robotic devices have been perceived usable so far, reflecting good acceptance in neuromotor rehabilitation programs. The limitations raised by the participants should be considered to further improve devices applicability and maximise technological rehabilitation effectiveness.

PROSPERO registration ref. CRD42021224141 .
PROSPERO registration ref. link3 CRD42021224141 .
Active learning situations such as simulation-based education (SBE) are found to trigger a wide range of emotions among students. Facilitators have an important educational role in SBE which include being attentive and adaptive to students'cognitive and affective responses. Although the importance of emotions in SBE is recognized in facilitator guidelines, little is known about how facilitators accommodate student affect. Hence, this study explores facilitators' strategies for addressing students' emotions in SBE.

Individual interviews with nine facilitators were performed and transcripts were subjected to qualitative analyses in accordance with interpretive description approach.

Findings show that facilitators are attentive to and continuously assess students' emotional responses in SBE. Both positive emotions, such as interest and surprise, and negative emotions such as anxiety are cultivated, yet adapted to the perceived needs of the individual student. Psychological safety was seen as a prerequisiteplexity of the facilitator's role in adapting training to individual cognitive and emotional needs. These findings have implications for facilitator training which should include awareness of the role of emotions in learning and strategies for observing and accommodating training to meet emotional needs.
The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property.

Herein, biocompatible Cu
SnS
nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu
SnS
NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu
SnS
NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu
SnS
NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu
SnS
NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection.

The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu
SnS
NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.
The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4 NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.
Simulation-Based Medical Education (SBME) is a teaching method commonly used in undergraduate medical education. Although Thai medical schools have developed a system that incorporates SBME, various aspects of that system require improvement. We surveyed medical school administrators, instructors, and students about SBME in their institutions and the obstacles involved in its implementation, as well as their experiences, expectations, and attitudes regarding the current system.

We conducted a cross-sectional online survey between August 2019 and July 2020 among administrators, instructors, and 6th-year medical students. A structured questionnaire was developed and distributed to volunteers as an online survey. We recorded details about the SBME system as well as participant characteristics, obstacles, experiences, expectations, and attitudes. We used descriptive statistics as appropriate.

We received responses from 15 (68.2%) administrators, 186 instructors, and 371 (13.7%) sixth-year medical students. s' expectations and need to be addressed. However, participants expressed positive attitudes toward SBME.

TCTR20210524003 (Thai Clinical Trials Registry).
TCTR20210524003 (Thai Clinical Trials Registry).
Our previous results have shown that obesity-induced excessive palmitic acid (PA) can promote the expression of KLF7, which plays a vital role in regulation of inflammation, glucose metabolism. But the exact mechanism of PA up-regulating the expression of KLF7 is not clear yet. This study is intend to explore whether PA promoting KLF7 expression through GPRs/NF-κB signaling pathway, causing inflammation and glucose metabolism disorders.

Cells were blocked GPRs/NF-κB under PA stimulation in vitro to demonstrate the molecular mechanism of PA up-regulates KLF7 expression. The regulatory effect of p65 on KLF7 was detected by luciferase reporter gene assay. Blocking GPRs/NF-κB in diet-induced obesity mice to detect the expression of KLF7, inflammatory cytokines and glucose metabolism related factors, clarifying the effects of GPRs/NF-κB on KLF7 in vivo.

In 3T3-L1 adipocytes and HepG2 cells, PA could up-regulate the expression of KLF7 by promoting the GPR40/120-NF-κB signaling pathway, leading to inflammation and reduced glucose consumption (p < 0.
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