Notes

Sticking with to be able to TB treatment method continues to be reduced in the course of extension stage between grownup sufferers throughout North west Ethiopia.
Influenza-specific CD8+ T-cells in BAL were highly enriched and predominantly expressed the Trm markers CD69 and CD103. Comparison between pre-infection CD8+ T-cells in BAL and blood by RNAseq revealed 3928 differentially expressed genes, including all major Trm cell markers. However, gene-set enrichment analysis of BAL CD8+ T-cells showed primarily innate cell-related pathways and, during infection, included upregulation of innate chemokines (Cxcl1, Cxcl10 and Cxcl16) that were also expressed by CD8+ cells in bronchial tissues.

CD8+ Trm cells in the human lung display innate-like gene and protein expression that demonstrates blurred divisions between innate and adaptive immunity. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02755948.
CD8+ Trm cells in the human lung display innate-like gene and protein expression that demonstrates blurred divisions between innate and adaptive immunity. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02755948.Purpose The purpose of the study was to determine the effect of hearing aid technology level on listener outcome measures. In addition, we aimed to determine if individual characteristics such as noise acceptance and the demands of the listening environment impacted performance and preference. Method A repeated-measures, single-blinded research design was utilized. Twenty-four adults recruited by mail from The University of Tennessee Health Science Center Audiology Clinic participated in this experiment (15 men and nine women). Participants completed two 2-week trial periods using Unitron T Moxi Fit FLEXTRIAL devices programmed as basic or premium technology levels. A data-logging feature, Log It All (LIA), quantified the demands of the listening environment. At the end of each trial, outcome measures were obtained using Pascoe's High-Frequency Word List, the Hearing in Noise Test, the Quick Speech-in-Noise Test, the Acceptable Noise Level (ANL), the Speech, Spatial and Qualities of Hearing short form, satisfcceptance and listening demands may be useful when comparing hearing aid technology levels for a given patient.All modern crocodyliforms (alligators, crocodiles and the gharial) are semi-aquatic generalist carnivores that are relatively similar in cranial form and function. However, this homogeneity represents just a fraction of the variation that once existed in the clade, which includes extinct herbivorous and marine forms with divergent skull structure and function. Here, we use high-dimensional three-dimensional geometric morphometrics to quantify whole-skull morphology across modern and fossil crocodyliforms to untangle the factors that shaped the macroevolutionary history and relatively low phenotypic variation of this clade through time. Evolutionary modelling demonstrates that the pace of crocodyliform cranial evolution is initially high, particularly in the extinct Notosuchia, but slows near the base of Neosuchia, with a late burst of rapid evolution in crown-group crocodiles. Surprisingly, modern crocodiles, especially Australian, southeast Asian, Indo-Pacific species, have high rates of evolution, despite exhibiting low variation. Thus, extant lineages are not in evolutionary stasis but rather have rapidly fluctuated within a limited region of morphospace, resulting in significant convergence. The structures related to jaw closing and bite force production (e.g. pterygoid flange and quadrate) are highly variable, reinforcing the importance of function in driving phenotypic variation. Together, these findings illustrate that the apparent conservativeness of crocodyliform skulls betrays unappreciated complexity in their macroevolutionary dynamics.The xylem sap of vascular plants is an unlikely source of nutrition, being both nutrient poor and held under tensions (negative pressures) that can exceed 1 MPa. But some insects feed on xylem sap exclusively, extracting copious quantities using a muscular cibarial pump. However, neither the strength of the insect's suction, nor the direct energetic cost of xylem ingestion, have ever been quantified. Philaenus spumarius froghoppers were used to address these gaps in our knowledge. Micro-CT scans of its cibarium and measurements of cibarial muscle sarcomere length revealed that P. spumarius can generate a maximum tension of 1.3 ± 0.2 MPa within its cibarium. The energetic cost of xylem extraction was quantified using respirometry to measure the metabolic rate (MR) of P. spumarius while they fed on hydroponically grown legumes, while xylem sap excretion rate and cibarial pumping frequency were simultaneously recorded. Increasing the plants' xylem tensions up to 1.1 MPa by exposing their roots to polyethylene glycol did not reduce the insects' rate of xylem excretion, but significantly increased both MR and pumping frequency. We conclude that P. spumarius can gain energy feeding on xylem sap containing previously reported energy densities and at xylem tensions up to their maximum suction capacity.Preprints are manuscripts posted on a public server that do not yet have formal certification of peer review from a scholarly journal. The increasingly prominent online repositories for these preprints provide a means of rapidly making scientific results accessible to all with an Internet connection. We here describe the catalysis and subsequent development of a successful new process to solicit preprints for consideration for publication in Proceedings B. We present preliminary comparisons between the focal topics and geographic origin of submitting authors of papers submitted in the traditional (non-solicited) route versus solicited preprints. This analysis suggests that the solicitation process seems to be achieving one of the primary goals of the preprint solicitation endeavour broadening the scope of the papers featured in Proceedings B. We also use an informal survey of the early-career scientists that are or have been involved with the Preprint Editorial Team to find that these scientists view their participation positively with respect to career development and knowledge in their field. The inclusion of early-career researchers from across the world in the preprint solicitation process could also translate into social justice benefits by providing a career-building opportunity and a window into the publishing process for young scientists.The earliest widely accepted presence of humans in America dates to approximately 17.5 cal kyr BP, at the end of the Last Glacial Maximum (LGM). Among other evidence, this presence is attested by stone tools and associated cut-marks and other bone surface modifications (BSM), interpreted as the result of the consumption of animals by humans. Claims of an older human presence in the continent have been made based on the proposed anthropogenic modification of faunal remains; however, these have been controversial due to the highly subjective nature of the interpretations. Here, we employ advanced deep learning algorithms to objectively increase the accuracy of BSM identification on bones. With several models that exhibit BSM classification accuracies greater than 94%, we use ensemble learning techniques to robustly classify a selected sample of BSM from the approximately 30 kyr BP site of Arroyo del Vizcaíno, Uruguay. Our results confidently show the presence of cut-marks imparted by stone tools on bones at the site. This result supports an earlier presence of humans in the American continent, expanding additional genetic and archaeological evidence of a human LGM and pre-LGM presence in the continent.The ability to rapidly detect and respond to wildlife morbidity and mortality events is critical for reducing threats to wildlife populations. Surveillance systems that use pre-diagnostic clinical data can contribute to the early detection of wildlife morbidities caused by a multitude of threats, including disease and anthropogenic disturbances. Here, we demonstrate proof of concept for use of a wildlife disease surveillance system, the 'Wildlife Morbidity and Mortality Event Alert System', that integrates pre-diagnostic clinical data in near real-time from a network of wildlife rehabilitation organizations, for early and enhanced detection of unusual wildlife morbidity and mortality events. The system classifies clinical pre-diagnostic data into relevant clinical classifications based on a natural language processing algorithm, generating alerts when more than the expected number of cases is recorded across the rehabilitation network. We demonstrated the effectiveness and efficiency of the system in alerting to events associated with both common and emerging diseases. Tapping into this readily available unconventional general surveillance data stream offers added value to existing wildlife disease surveillance programmes through a relatively efficient, low-cost strategy for the early detection of threats.Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter-gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.In collective animal motion, coordination is often achieved by feedback between leaders and followers. For stable coordination, a leader's signals and a follower's responses are hypothesized to be attuned to each other. However, their roles are difficult to disentangle in species with highly coordinated movements, hiding potential diversity of behavioural mechanisms for collective behaviour. Here, we show that two Coptotermes termite species achieve a similar level of coordination via distinct sets of complementary leader-follower interactions. Even though C. gestroi females produce less pheromone than C. formosanus, tandem runs of both species were stable. Heterospecific pairs with C. gestroi males were also stable, but not those with C. formosanus males. We attributed this to the males' adaptation to the conspecific females; C. gestroi males have a unique capacity to follow females with small amounts of pheromone, while C. formosanus males reject C. gestroi females as unsuitable but are competitive over females with large amounts of pheromone. An information-theoretic analysis supported this conclusion by detecting information flow from female to male only in stable tandems. Our study highlights cryptic interspecific variation in movement coordination, a source of novelty for the evolution of social interactions.Modern plague outbreaks exhibit a distinct seasonal pattern. By contrast, the seasonality of historical outbreaks and its drivers has not been studied systematically. Here, we investigate the seasonal pattern, the epidemic peak timing and growth rates, and the association with latitude, temperature, and precipitation using a large, novel dataset of plague- and all-cause mortality during the Second Pandemic in Europe and the Mediterranean. We show that epidemic peak timing followed a latitudinal gradient, with mean annual temperature negatively associated with peak timing. Based on modern temperature data, the predicted epidemic growth of all outbreaks was positive between 11.7°C and 21.5°C with a maximum around 17.3°C. Hence, our study provides evidence that the growth of plague epidemics across the whole study region depended on similar absolute temperature thresholds. Here, we present a systematic analysis of the seasonality of historical plague in the Northern Hemisphere, and we show consistent evidence for a temperature-related process influencing the epidemic peak timing and growth rates of plague epidemics.Wildfires are a natural disturbance in many ecosystems. However, their effect on biotic interactions has been poorly studied. Fire consumes the vegetation and the litter layer where many parasites spend part of their life cycles. We hypothesize that wildfires reduce habitat availability for parasites with consequent potential benefits for hosts. We tested this for the lizard Psammodromus algirus and its ectoparasites in a Mediterranean ecosystem. We predicted that lizards in recently burned areas would have lower parasite load (cleaning effect) than those in unburned areas and that this phenomenon implies that lizards spending their entire lives in postfire conditions experience a lower level of parasitism than those living in unburned areas. We compared the ectoparasite load of lizards between eight paired burned/unburned sites, including recent (less than 1 year postfire) and older fires (2-4 years). We found that lizards' ectoparasites prevalence was drastically reduced in recently burned areas. Likewise, lizards in older burned areas showed less evidence of past parasitic infections. Fire disrupted the host-parasite interaction, providing the opportunity for lizards to avoid the negative effects of ectoparasites. Our results suggest that wildfires probably fulfil a role in controlling vector-borne diseases and pathogens, and highlight ecological effects of wildfires that have been overlooked.Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth (a) the improvement of mainstream additive manufacturing methods and associated feedstock; (b) the exploration of mature, less utilized metal 3D printing techniques; (c) the optimization of additively manufactured load-bearing structures via artificial intelligence; and (d) the creation of monolithic, multimaterial, finely featured, multifunctional implants.Cells of the vascular wall are exquisitely sensitive to changes in their mechanical environment. In healthy vessels, mechanical forces regulate signaling and gene expression to direct the remodeling needed for the vessel wall to maintain optimal function. Major diseases of arteries involve maladaptive remodeling with compromised or lost homeostatic mechanisms. Whereas homeostasis invokes negative feedback loops at multiple scales to mediate mechanobiological stability, disease progression often occurs via positive feedback that generates mechanobiological instabilities. In this review, we focus on the cell biology, wall mechanics, and regulatory pathways associated with arterial health and how changes in these processes lead to disease. We discuss how positive feedback loops arise via biomechanical and biochemical means. We conclude that inflammation plays a central role in overriding homeostatic pathways and suggest future directions for addressing therapeutic needs.The blood-brain barrier (BBB) is one of the most selective endothelial barriers. An understanding of its cellular, morphological, and biological properties in health and disease is necessary to develop therapeutics that can be transported from blood to brain. In vivo models have provided some insight into these features and transport mechanisms adopted at the brain, yet they have failed as a robust platform for the translation of results into clinical outcomes. In this article, we provide a general overview of major BBB features and describe various models that have been designed to replicate this barrier and neurological pathologies linked with the BBB. We propose several key parameters and design characteristics that can be employed to engineer physiologically relevant models of the blood-brain interface and highlight the need for a consensus in the measurement of fundamental properties of this barrier.Photoactive agents are promising complements for both early diagnosis and targeted treatment of cancer. The dual combination of diagnostics and therapeutics is known as theranostics. Photoactive theranostic agents are activated by a specific wavelength of light and emit another wavelength, which can be detected for imaging tumors, used to generate reactive oxygen species for ablating tumors, or both. Photodynamic therapy (PDT) combines photosensitizer (PS) accumulation and site-directed light irradiation for simultaneous imaging diagnostics and spatially targeted therapy. Although utilized since the early 1900s, advances in the fields of cancer biology, materials science, and nanomedicine have expanded photoactive agents to modern medical treatments. In this review we summarize the origins of PDT and the subsequent generations of PSs and analyze seminal research contributions that have provided insight into rational PS design, such as photophysics, modes of cell death, tumor-targeting mechanisms, and light dosing regimens. We highlight optimizable parameters that, with further exploration, can expand clinical applications of photoactive agents to revolutionize cancer diagnostics and treatment.The host-to-host transmission of respiratory infectious diseases is fundamentally enabled by the interaction of pathogens with a variety of fluids (gas or liquid) that shape pathogen encapsulation and emission, transport and persistence in the environment, and new host invasion and infection. Deciphering the mechanisms and fluid properties that govern and promote these steps of pathogen transmission will enable better risk assessment and infection control strategies, and may reveal previously underappreciated ways in which the pathogens might actually adapt to or manipulate the physical and chemical characteristics of these carrier fluids to benefit their own transmission. In this article, I review our current understanding of the mechanisms shaping the fluid dynamics of respiratory infectious diseases.There is a need for a systematic approach to evaluate patients for potential face transplantation (FT). Ten patients with severe facial defects treated between 1995 and 2017 formed the study group. Data was collected from patient charts and clinical, radiological and laboratory examinations. Facial deficiencies were subdivided into four different categories anatomical region (10 facial subunits), facial function, aesthetic defect (range 0-9-worst), and impact on health-related quality of life (HRQoL) (15D questionnaire, range 0-1). Immunological status and possible contraindications were also evaluated. Defect aetiology consisted of burns (4), ballistic injury (3), blunt injury (1), blast injury (1), and neurofibromatosis type I (1). All patients had central facial deficiencies and 6 patients had 8 to 10 injured facial subunits. All patients had at least partial loss of facial function. The mean aesthetic disfigurement score was 6.4. The median lowering of 15D score was -0.107. None were significantly sensitized although four patients had relative contraindications and one patient had an absolute contraindication for FT. Three patients with a severe overall facial deficiency were considered as potential FT candidates. We herein propose a comprehensive and systematic tool to evaluate potential candidates for FT. This approach includes assessment of 4 key categories anatomical regions affected, facial function, aesthetics, and HRQoL.This study compared activity participation, and mental and physical functions of two different groups of adults with chronic cardiac conditions. Eleven participants were assessed at the immediate post-acute stage and 26 participants were at the distant post-acute stage. Participants at distant post-acute were significantly more physically active (p less then .001), more activity-limited in cognition-related activities (p = .035) and reported more depressive symptoms than immediate post-acute (p = .046). No significant difference in participation level was found. More attention to functional cognition and depressive symptoms at immediate post-acute and individualized approaches to remove participation barriers in complex activities at distant post-acute are likely needed for adults with chronic cardiac conditions.African elephants (Loxodonta africana) are sentient and intelligent animals that use a variety of vocalizations to greet, warn or communicate with each other. Their low-frequency rumbles propagate through the air as well as through the ground and the physical properties of both media cause differences in frequency filtering and propagation distances of the respective wave. However, it is not well understood how each mode contributes to the animals' abilities to detect these rumbles and extract behavioural or spatial information. In this study, we recorded seismic and co-generated acoustic rumbles in Kenya and compared their potential use to localize the vocalizing animal using the same multi-lateration algorithms. For our experimental set-up, seismic localization has higher accuracy than acoustic, and bimodal localization does not improve results. We conclude that seismic rumbles can be used to remotely monitor and even decipher elephant social interactions, presenting us with a tool for far-reaching, non-intrusive and surprisingly informative wildlife monitoring.Nearly all animals forage to acquire energy for survival through efficient search and resource harvesting. Patch exploitation is a canonical foraging behaviour, but there is a need for more tractable and understandable mathematical models describing how foragers deal with uncertainty. To provide such a treatment, we develop a normative theory of patch foraging decisions, proposing mechanisms by which foraging behaviours emerge in the face of uncertainty. Our model foragers statistically and sequentially infer patch resource yields using Bayesian updating based on their resource encounter history. A decision to leave a patch is triggered when the certainty of the patch type or the estimated yield of the patch falls below a threshold. The time scale over which uncertainty in resource availability persists strongly impacts behavioural variables like patch residence times and decision rules determining patch departures. When patch depletion is slow, as in habitat selection, departures are characterized by a reduction of uncertainty, suggesting that the forager resides in a low-yielding patch. Uncertainty leads patch-exploiting foragers to overharvest (underharvest) patches with initially low (high) resource yields in comparison with predictions of the marginal value theorem. These results extend optimal foraging theory and motivate a variety of behavioural experiments investigating patch foraging behaviour.In gliding flight, birds morph their wings and tails to control their flight trajectory and speed. Using high-resolution videogrammetry, we reconstructed accurate and detailed three-dimensional geometries of gliding flights for three raptors (barn owl, Tyto alba; tawny owl, Strix aluco, and goshawk, Accipiter gentilis). Wing shapes were highly repeatable and shoulder actuation was a key component of reconfiguring the overall planform and controlling angle of attack. The three birds shared common spanwise patterns of wing twist, an inverse relationship between twist and peak camber, and held their wings depressed below their shoulder in an anhedral configuration. With increased speed, all three birds tended to reduce camber throughout the wing, and their wings bent in a saddle-shape pattern. A number of morphing features suggest that the coordinated movements of the wing and tail support efficient flight, and that the tail may act to modulate wing camber through indirect aeroelastic control.Recently, two coronavirus disease 2019 (COVID-19) vaccine products have been authorized in Canada. It is of crucial importance to model an integrated/combined package of non-pharmaceutical (physical/social distancing) and pharmaceutical (immunization) public health control measures. A modified epidemiological, compartmental SIR model was used and fit to the cumulative COVID-19 case data for the province of Ontario, Canada, from 8 September 2020 to 8 December 2020. Different vaccine roll-out strategies were simulated until 75% of the population was vaccinated, including a no-vaccination scenario. We compete these vaccination strategies with relaxation of non-pharmaceutical interventions. Non-pharmaceutical interventions were supposed to remain enforced and began to be relaxed on 31 January, 31 March or 1 May 2021. Based on projections from the data and long-term extrapolation of scenarios, relaxing the public health measures implemented by re-opening too early would cause any benefits of vaccination to be lost by increasing case numbers, increasing the effective reproduction number above 1 and thus increasing the risk of localized outbreaks. If relaxation is, instead, delayed and 75% of the Ontarian population gets vaccinated by the end of the year, re-opening can occur with very little risk. Relaxing non-pharmaceutical interventions by re-opening and vaccine deployment is a careful balancing act. Our combination of model projections from data and simulation of different strategies and scenarios, can equip local public health decision- and policy-makers with projections concerning the COVID-19 epidemiological trend, helping them in the decision-making process.This clinical consensus document addresses the assessment, selection, and fitting considerations for non-surgical bone conduction hearing devices (BCHD) for children under the age of 5 years identified as having unilateral or bilateral, permanent conductive or mixed hearing losses. Children with profound unilateral sensorineural hearing losses are not addressed. The document was developed based on evidence review and consensus by The Paediatric Bone Conduction Working Group, which is composed of audiologists from North America who have experience working with BCHDs in children. The document aims to provide clinical direction for an area of paediatric audiology practice that is under development and is therefore lacking in standard protocols or guidelines. This work may serve as a basis for future research and clinical contributions to support prospective paediatric audiology practices.Myostatin is a negative regulator of skeletal muscle and has become a therapeutic target for muscle atrophying disorders. Although previous inhibitors of myostatin offered promising preclinical data, these therapies demonstrated a lack of specificity toward myostatin signaling and have shown limited success in the clinic. Apitegromab is a fully human, monoclonal antibody that binds to human promyostatin and latent myostatin with a high degree of specificity, without binding mature myostatin and other closely related growth factors. To support the clinical development of apitegromab, we present data from a comprehensive preclinical assessment of its pharmacology, pharmacokinetics, and safety across multiple species. In vitro studies confirmed the ability of apitegromab to inhibit the activation of promyostatin. Toxicology studies in monkeys for 4 weeks and in adult rats for up to 26 weeks showed that weekly intravenous administration of apitegromab achieved sustained serum exposure and target engagement and was well-tolerated, with no treatment-related adverse findings at the highest doses tested of up to 100 mg/kg and 300 mg/kg in monkeys and rats, respectively. Additionally, results from an 8-week juvenile rat study showed no adverse effects on any endpoint, including neurodevelopmental, motor, and reproductive outcomes at 300 mg/kg administered weekly IV. In summary, the nonclinical pharmacology, pharmacokinetic, and toxicology data demonstrate that apitegromab is a selective inhibitor of proforms of myostatin that does not exhibit toxicities observed with other myostatin pathway inhibitors. These data support the conduct of ongoing clinical studies of apitegromab in adult and pediatric patients with spinal muscular atrophy (SMA).Purpose Developmental language disorder (DLD) is defined by persistent difficulties with language, but a growing body of evidence suggests that it is also associated with domain-general and nonverbal information-processing deficits. However, the interconnections between cognitive functions, both nonverbal and language related, are still unclear. With the aim of gaining more comprehensive insight into the cognitive deficits related to DLD, we investigated and compared the cognitive structure of children with DLD and typically developing (TD) children. Method As a part of the Helsinki longitudinal SLI study, monolingual Finnish preschoolers (N = 154; TD group n = 66, DLD group n = 88) were assessed with 23 tasks measuring nonverbal and verbal reasoning, language processing, memory, visuomotor functions, attention, and social cognition. Exploratory factor analysis and structural equation modeling were performed to examine latent constructs and to test measurement invariance between the TD and DLD groups. Results Measurement invariance was not found across the TD and DLD groups. Best fitting structure for TD children included factors reflecting verbal abilities, processing speed/short-term memory, visuomotor functions, and visuoconstructive abilities/nonverbal reasoning. The DLD group's structure comprised nonverbal abilities, naming/expressive language, verbal comprehension, and verbal/declarative memory. Conclusions The findings suggest that the structure of cognitive functions differs in TD children and children with DLD already at preschool age. Nonverbal functions seem more unified, whereas verbal functions seem more varying in preschoolers with DLD compared to TD children. The results can be used in future research for prognosis of DLD and planning interventions.Purpose Learning spoken words can be challenging for children with hearing loss who communicate orally and who are known to have weaker oral vocabulary skills than age-matched children who hear. Since vocabulary skills play a crucial role in reading and literacy acquisition, and academic success, it is important to identify effective vocabulary acquisition strategies for children with hearing loss. The aim of this study was to examine whether the incidental presence of orthography can facilitate oral vocabulary learning in children with hearing loss and whether the benefits are greater than those found in hearing children. Method We taught novel picture-word pairs with or without spellings to 23 children with hearing loss and 23 age-matched controls, ranging in age from 6 to 12 years. Word learning was assessed using behavioral and eye tracking data from picture naming and picture-word matching tasks. Results and Conclusions Results revealed an orthographic facilitation effect on oral vocabulary learning in children with hearing loss, with benefits being maintained over a week. Importantly, children with hearing loss showed a greater benefit of orthography than age-matched hearing peers on the picture naming tests. The results of this study have important implications for classroom instruction and vocabulary instruction strategies for children with hearing loss.Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) plays positive roles in the growth, proliferation of cells and early embryos development by binding mRNA targets. Recently, it had been shown that some polymorphic loci within IGF2BP1 gene were associated with growth traits in animals, especially in goats. Therefore, it has been hypothesized that some variants within IGF2BP1 gene may be also involved in growth traits of sheep. Nine insertion/deletion (InDel) mutations within IGF2BP1 were identified and three loci were polymorphic. Meanwhile, the association analyses between three InDels and growth traits were carried out in 745 sheep. The results showed that all InDels included 5 bp InDel in downstream region, 9 bp InDel in intron 4 and 15 bp InDel in intron 2 within IGF2BP1 were significantly associated with growth traits (p less then .05). Furthermore, at 5 and 9 bp InDel loci, the individuals of heterozygous genotype (ID) had superior growing performance especially at body weight (BW). In all, three InDels were crucial variants correlated with growth traits and could be applied in marker-assisted selection (MAS) in sheep.Purpose The purpose of this study was to develop and pilot a novel treatment framework called BEARS (Balancing Effort, Accuracy, and Response Speed). People with aphasia (PWA) have been shown to maladaptively balance speed and accuracy during language tasks. BEARS is designed to train PWA to balance speed-accuracy trade-offs and improve system calibration (i.e., to adaptively match system use with its current capability), which was hypothesized to improve treatment outcomes by maximizing retrieval practice and minimizing error learning. In this study, BEARS was applied in the context of a semantically oriented anomia treatment based on semantic feature verification (SFV). Method Nine PWA received 25 hr of treatment in a multiple-baseline single-case series design. BEARS + SFV combined computer-based SFV with clinician-provided BEARS metacognitive training. Naming probe accuracy, efficiency, and proportion of "pass" responses on inaccurate trials were analyzed using Bayesian generalized linear mixed-effects moof BEARS + SFV and provides preliminary evidence for its efficacy. This study highlights the importance of considering processing efficiency in anomia treatment, in addition to performance accuracy. Supplemental Material https//doi.org/10.23641/asha.14935812.Trehalose is a versatile non-reducing sugar. In some animal groups possessing its intrinsic production machinery, it is used as a potent protectant against environmental stresses, as well as blood sugar. However, the trehalose biosynthesis genes remain unidentified in the large majority of metazoan phyla, including vertebrates. To uncover the evolutionary history of trehalose production machinery in metazoans, we scrutinized the available genome resources and identified bifunctional trehalose-6-phosphate synthase-trehalose-6-phosphate phosphatase (TPS-TPP) genes in various taxa. The scan included our newly sequenced genome assembly of a desiccation-tolerant tardigrade Paramacrobiotus sp. TYO, revealing that this species retains TPS-TPP genes activated upon desiccation. Phylogenetic analyses identified a monophyletic group of the many of the metazoan TPS-TPP genes, namely 'pan-metazoan' genes, that were acquired in the early ancestors of metazoans. Furthermore, coordination of our results with the previous horizontal gene transfer studies illuminated that the two tardigrade lineages, nematodes and bdelloid rotifers, all of which include desiccation-tolerant species, independently acquired the TPS-TPP homologues via horizontal transfer accompanied with loss of the 'pan-metazoan' genes. Our results indicate that the parallel evolution of trehalose synthesis via recurrent loss and horizontal transfer of the biosynthesis genes resulted in the acquisition and/or augmentation of anhydrobiotic lives in animals.Teleost fish are the most diverse group of vertebrates and provide opportunities to study the evolution of sex determination (SD) systems. Using genomic and functional analyses, we identified a male-specific duplication of anti-Müllerian hormone (amh) gene as the male master sex-determining (MSD) gene in Sebastes schlegelii. By resequencing 10 males and 10 females, we characterized a 5 kb-long fragment in HiC_Scaffold_12 as a male-specific region, which contained an amh gene (named amhy). We then demonstrated that amhy is a duplication of autosomal amh that was later translocated to the ancestral Y chromosome. amha and amhy shared high-nucleotide identity with the most significant difference being two insertions in intron 4 of amhy. Furthermore, amhy overexpression triggered female-to-male sex reversal in S. schlegelii, displaying its fundamental role in driving testis differentiation. We developed a PCR assay which successfully identified sexes in two species of northwest Pacific rockfish related to S. schlegelii. However, the PCR assay failed to distinguish the sexes in a separate clade of northeast Pacific rockfish. Our study provides new examples of amh as the MSD in fish and sheds light on the convergent evolution of amh duplication as the driving force of sex determination in different fish taxa.Successful navigation of the mouse preimplantation stages of development, during which three distinct blastocyst lineages are derived, represents a prerequisite for continued development. We previously identified a role for p38-mitogen-activated kinases (p38-MAPK) regulating blastocyst inner cell mass (ICM) cell fate, specifically primitive endoderm (PrE) differentiation, that is intimately linked to rRNA precursor processing, polysome formation and protein translation regulation. Here, we develop this work by assaying the role of DEAD-box RNA helicase 21 (DDX21), a known regulator of rRNA processing, in the context of p38-MAPK regulation of preimplantation mouse embryo development. We show nuclear DDX21 protein is robustly expressed from the 16-cell stage, becoming exclusively nucleolar during blastocyst maturation, a localization dependent on active p38-MAPK. siRNA-mediated clonal Ddx21 knockdown within developing embryos is associated with profound cell-autonomous and non-autonomous proliferation defects and reduced blastocyst volume, by the equivalent peri-implantation blastocyst stage. Moreover, ICM residing Ddx21 knockdown clones express the EPI marker NANOG but rarely express the PrE differentiation marker GATA4. These data contribute further significance to the emerging importance of lineage-specific translation regulation, as identified for p38-MAPK, during mouse preimplantation development.SUMOylation dynamically conjugates SUMO molecules to the lysine residue of a substrate protein, which depends on the physiological state of the cell and the attached SUMO isoforms. A prominent role of SUMOylation in molecular pathways is to govern the cellular death process. Herein, we summarize the association between SUMOylation modification events and four types of cellular death processes apoptosis, autophagy, senescence and pyroptosis. SUMOylation positively or negatively regulates a certain cellular death pattern depending on specific conditions including the attached SUMO isoforms, disease types, substrate proteins and cell context. Moreover, we also discuss the possible role of SUMOylation in ferroptosis and propose a potential role of the SUMOylated GPX4 in the regulation of ferroptosis. Mapping the exact SUMOylation network with cellular death contributes to develop novel SUMOylation-targeting disease therapeutic strategies.
Prolonged mechanical ventilation (MV) is often associated either with a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a non-invasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties.

To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm.

Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets.

We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3+/-4.3 kPa and diaphragm end-expiratory thickness was 2.0+/-0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for shear modulus. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (β=-9.34±4.41; p=0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of MV was associated with loss of force production, slow and fast fiber atrophy and increased lipid droplets accumulation.

Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness.
Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness.Background Cardiovascular risk in diabetes remains elevated despite glucose lowering therapies. We hypothesised that hyperglycaemia induces trained immunity in macrophages, promoting persistent pro-atherogenic characteristics. Methods Bone marrow derived macrophages from control and mice with diabetes were grown in physiological glucose (5 mM) and subject to RNA-sequencing (n=6), ATAC-sequencing (n=6) and ChIP-sequencing (n=6) for determination of hyperglycaemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into [normoglycaemic] Ldlr -/- mice was used to assess its functional significance in vivo. Evidence of hyperglycaemia-induced trained immunity was sought in human peripheral blood mononuclear cells (PBMCs) from patients with diabetes (n=8) compared with case controls (n=16) and in human atherosclerotic plaque macrophages excised by laser capture microdissection. Results In macrophages, high extracellular glucose promoted pro-inflammatory gene expressinity may explain why targeting elevated glucose is ineffective in reducing macrovascular risk in diabetes and suggests new targets for disease prevention and therapy.We report the development of low-cost triboelectric nanogenerators (TENGs) based on polypropylene (PP) fabrics formulated via an inexpensive melt-blowing process with an output voltage as high as 50 V. By disinfection methods such as exposure to steam, ethanol, and dry heat at 75 °C, the commercial medical masks and N95 filtering facepiece respirators (FFRs) can be reused to fabricate PP fiber based TENGs, which provide a novel regime for energy-harvesting devices based on reusable materials. As a power source, the output of one TENG can drive 15 serially connected light-emitting diodes (LEDs) or a commercial electric calculator. PP fabric TENGs can also work as self-powered sensors for the high-sensitivity detection of mechanical impact. We provide examples where the TENG is used to detect biomechanical motion such as that associated with the extension of an elbow, the touch of a finger, the impact of footsteps, and the bending of a knee without an external power supply. Most importantly, these PP fabrics for TENGs can be obtained from decontaminated medical masks that are generated as tremendous wastes every day, which provide a great potential as sustainable energy. These properties suggest that PP fabric based TENGs are promising for harvesting energy from biological systems and that they may facilitate the large-scale production of a new range of inexpensive self-powered multifunctional wearable sensors for applications in healthcare, security, and information networks.We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl radical coupling reactions from abundant but difficult to reduce aryl chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled by a key terminal reductant byproduct, carbon dioxide radical anion.The correlation of the rotation about the Cα-C' bond and the pyramidalization of the sp2-hybridized carbon atom C' and its three bonding partners to a flattened tetrahedron in the substructure Cβ-CαH-C'(═O)-OMe of substituted methyl acetates revealed that the two processes are not independent of each other but parts of a common molecular motion, as outlined in the preceding back-to-back paper. In the present study, we generalized the substructure to Xβ-CαH-C'(═Y)-Z with X, Y, and Z = O, N, C, and S, extending the analysis to several hundred thousand structures of the type carboxylates, carboxamides, ketones, imines, olefins, peptides, lactates, carbothioates, and phenyl derivatives, retrieved from the Cambridge Structural Database. ψ/θ Scatter plots of the individual structure points and their averaging in ψ/θav curves result in wavelike patterns with three maxima and minima and inversion symmetry at ψ = 0° and ±180 for a 360° rotation of Cβ about the Cα-C' bond. The pyramidalization of the sp2-hybridized group CαCiCoCo', which is part of the aromatic system, even disturbs the planarity of phenyl rings. Density functional theory calculations confirm the results of the CSD search.Surfactants can significantly improve the oil recovery of spontaneous imbibition (SI) in unconventional oil reservoirs, but mathematical modeling of surfactant SI for displacing oil in a tight matrix is challenging because of its complex mechanism. Considering the mechanisms of surfactant diffusion and adsorption, the flow equation for the SI of surfactant solution into an oil-saturated capillary is derived, and the dynamic capillary pressure and surfactant concentration during the SI process are characterized. Then, based on the pore size distribution of the pores in a tight matrix, a core-scale mathematical model for SI of surfactant solution into an oil-saturated tight matrix is developed and validated with experimental data from the literature. The results show that surfactant adsorption can increase the product of interfacial tension and the cosine of the contact angle, and the increased capillary pressure in pores leads to a faster imbibition rate. A surfactant with a high adsorption and desorption rate on the water-solid interface and diffusion ability will lead to a higher oil production rate by SI in unconventional oil reservoirs. The proposed model is beneficial for modeling the dynamic process of surfactant SI and screening suitable surfactants for enhanced oil recovery in unconventional reservoirs.In the past, various chiral isomers accompanied by electroactive units have been distinguished using electrochemical techniques, which can produce electrochemical signals by themselves. However, it is still difficult to use an electrochemical technique to detect nonelectroactive samples. To address this bottleneck, an electroactive chiral polymer (S,S)-p-CVB-Fc that contains one redox-active ferrocene unit was designed and synthesized in this study. The electroactive polymer can give electrochemical signals as an alternative to the tested chiral samples, regardless of whether the isomers have electroactive units. Then, it was fixed on the surface of a glassy carbon electrode as an electrochemical chiral sensor. When nonelectroactive amino acids including proline, threonine, and alanine were examined by the sensor, clear discrimination in the response of peak current could be observed toward l- and d-isomers at pH 6.5. The peak current ratios (IL/ID) for proline and alanine were 1.47 and 1.48, respectively. In contrast, for threonine, the d-isomer exhibited a higher peak current than the l -isomer with a ratio of 2.59. In summary, the results ensure that the current work can enlarge the testing scope of chiral samples in the field of chiral electroanalysis using an electroactive sensor.The next generation of green insulation materials is being developed to provide safer and more sustainable alternatives to conventional materials. Bio-based cellulose nanofiber (CNF) aerogels offer excellent thermal insulation properties; however, their high flammability restricts their application. In this study, the design concept for the development of a multifunctional and non-toxic insulation material is inspired by the natural composition of seaweed, comprising both alginate and cellulose. The approach includes three steps first, CNFs were separated from alginate-rich seaweed to obtain a resource-efficient, fully bio-based, and inherently flame-retardant material; second, ice-templating, followed by freeze-drying, was employed to form an anisotropic aerogel for effective insulation; and finally, a simple crosslinking approach was applied to improve the flame-retardant behavior and stability. At a density of 0.015 g cm-3, the lightweight anisotropic aerogels displayed favorable mechanical properties, including a compressive modulus of 370 kPa, high thermal stability, low thermal conductivity (31.5 mW m-1 K-1), considerable flame retardancy (0.053 mm s-1), and self-extinguishing behavior, where the inherent characteristics were considerably improved by crosslinking. Different concentrations of the crosslinker altered the mechanical properties, while the anisotropic structure influenced the mechanical properties, combustion velocity, and to some extent thermal conductivity. Seaweed-derived aerogels possess intrinsic characteristics that could serve as a template for the future development of sustainable high-performance insulation materials.A series of β-ketoamino-based N,O-chelate half-sandwich iridium complexes with the general formula [Cp*IrClL] have been prepared in good yields. These air-insensitive iridium complexes showed desirable catalytic activity in an amide preparation under mild conditions. A number of amides with diverse substituted groups were furnished in a one-pot reaction with good-to-excellent yields through an amidation reaction of NH2OH·HCl with aldehydes in the presence of these iridium(III) precursors. The excellent catalytic activity, mild reaction conditions, and broad substrate scope gave this type of iridium catalyst potential for use in industry. All of the obtained iridium complexes were well characterized by different spectroscopy techniques. The exact molecular structure of complex 3 has been confirmed by single-crystal X-ray analysis.
My Website: