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Albinism is an uncommon phenomenon and inherited condition in animals characterized by a partial or complete lack of melanin. The family Xenodermidae Gray, 1849, is a group of caenophidian snakes widely distributed in South, East, and Southeast Asia, including five recognized genera and 36 species. However, there are currently no reports of albinism in any species in Xenodermidae. Achalinus sheni Ma, Xu, Qi, Wang, Tang, Huang & Jiang, 2023 was first described based on five male specimens from Loudi City and Nanyue District, Hunan Province, China. At the time, there were no descriptions on female individuals. In this study, we report in detail a collected albinistic specimen of A. sheni, which is the first discovery of wild albinism in the family Xenodermidae. We also provide photographs and descriptions of the first three female specimens of A. sheni and extend the diagnosis of this species.

Abstract Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419))

The present study sought to replicate two non-intuitive effects reported in the literature on lateral manual interception of uniformly moving targets, the angle-of-approach (AoA) effect and the reversal-movement (RM) effect. Both entail an influence of the target trajectory’s incidence angle on the observed interceptive hand movements along the interception axis; they differ in the interception location considered. The AoA effect concerns all trajectory conditions requiring hand movement to allow successful interception, while the RM effect concerns the particular condition where the target will in fact arrive at the hand’s initial position and no hand movement is therefore required but nevertheless regularly produced. Whereas the AoA effect has been systematically replicated, the RM effect has not. To determine whether the RM effect is in fact a reproducible phenomenon, we deployed a procedure enhancing the uncertainty about the target’s future arrival locations with respect to the hand’s initial position and included low-to-high target motion speeds. Results demonstrated the presence of both the AoA effect and the RM effect. The AoA effect was observed for all relevant interception locations, with the effect being stronger for the farther interception locations and the lower target speeds. The RM effect, with the hand first moving away from its initial position, in the direction of the target, before reversing direction, was observed in a higher proportion of trials for target trajectories with larger incidence angles and lower speeds. Earlier initiation gave rise to reversal movements of larger amplitude. Both effects point to visual guidance of hand movement partially based in reliance on information with respect to current lateral ball position. We conclude that the information used in lateral manual interception is of an intermediate order, which can be conceived as resulting from a partial combination of target position and velocity information or information in the form of a fractional order derivative.

Abstract The outcomes of speciation across organismal dimensions (e.g., ecological, genetic, phenotypic) are often assessed using phylogeographic methods. At one extreme, reproductively isolated lineages represent easily delimitable species differing in many or all dimensions, and at the other, geographically distinct genetic segments introgress across broad environmental gradients with limited phenotypic disparity. In the ambiguous gray zone of speciation, where lineages are genetically delimitable but still interacting ecologically, it is expected that these lineages represent species in the context of ontology and the evolutionary species concept when they are maintained over time with geographically well‐defined hybrid zones, particularly at the intersection of distinct environments. As a result, genetic structure is correlated with environmental differences and not space alone, and a subset of genes fail to introgress across these zones as underlying genomic differences accumulate. We present a set of tests that synthesize species delimitation with the speciation process. We can thereby assess historical demographics and diversification processes while understanding how lineages are maintained through space and time by exploring spatial and genome clines, genotype‐environment interactions, and genome scans for selected loci. Employing these tests in eight lineage‐pairs of snakes in North America, we show that six pairs represent 12 “good” species and that two pairs represent local adaptation and regional population structure. The distinct species pairs all have the signature of divergence before or near the mid‐Pleistocene, often with low migration, stable hybrid zones of varying size, and a subset of loci showing selection on alleles at the hybrid zone corresponding to transitions between distinct ecoregions. Locally adapted populations are younger, exhibit higher migration, and less ecological differentiation. Our results demonstrate that interacting lineages can be delimited using phylogeographic and population genetic methods that properly integrate spatial, temporal, and environmental data.

Long-term wildlife research and monitoring programs strive to maintain consistent data collections and analytical methods. Incorporating new techniques is important but can render data sets incongruent and limit their potential to discern trends in demographic parameters. Integrated population models (IPMs) can address these limitations by combining data sources that may span different periods into a unified statistical framework while providing a holistic view of population dynamics. We developed an IPM in a Bayesian framework for grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem. We coupled demographic data with multiple, independent population count data to link annual changes in abundance with vital rates over 4 decades (1983–2023). Abundance increased threefold from an estimated 270 individuals in 1984 to 1030 individuals in 2023. Parameter estimates indicated survival of bears ≥2 years of age was high, contributing to robust population growth during the 1980s (λ = 1.023 [50 % interquartile range = 0.993–1.082]) and 1990s (λ = 1.064 [1.023–1.103]). A slowing of population growth started around 2000 (2000s: λ = 1.030 [0.989–1.068]) and continued into the 2010s (λ = 1.021 [0.985–1.057]), due primarily to reductions in survival of bears

With a renewed focus on health equity in the United States driven by national crises and legislation to improve digital healthcare innovation, there is a need for the designers of digital health tools to take deliberate steps to design for equity in their work. A concrete toolkit of methods to design for health equity is needed to support digital health practitioners in this aim. This narrative review summarizes several health equity frameworks to help digital health practitioners conceptualize the equity dimensions of importance for their work, and then provides design approaches that accommodate an equity focus. Specifically, the Double Diamond Model, the IDEAS framework and toolkit, and community collaboration techniques such as participatory design are explored as mechanisms for practitioners to solicit input from members of underserved groups and better design digital health tools that serve their needs. Each of these design methods requires a deliberate effort by practitioners to infuse health equity into the approach. A series of case studies that use different methods to build in equity considerations are offered to provide examples of how this can be accomplished and demonstrate the range of applications available depending on resources, budget, product maturity, and other factors. We conclude with a call for shared rigor around designing digital health tools that deliver equitable outcomes for members of underserved populations.

Estimation of evolutionary relationships among lineages that rapidly diversified can be challenging, and, in such instances, inaccurate or unresolved phylogenetic estimates can lead to erroneous conclusions regarding historical geographical ranges of lineages. One example underscoring this issue has been the historical challenge posed by untangling the biogeographic origin of elapoid snakes, which includes numerous dangerously venomous species as well as species not known to be dangerous to humans. The worldwide distribution of this lineage makes it an ideal group for testing hypotheses related to historical faunal exchanges among the many continents and other landmasses occupied by contemporary elapoid species. We developed a novel suite of genomic resources, included worldwide sampling, and inferred a robust estimate of evolutionary relationships, which we leveraged to quantitatively estimate geographical range evolution through the deep-time history of this remarkable radiation. Our phylogenetic and biogeographical estimates of historical ranges definitively reject a lingering former ‘Out of Africa’ hypothesis and support an ‘Out of Asia’ scenario involving multiple faunal exchanges between Asia, Africa, Australasia, the Americas and Europe.

Phrenic nerve stimulation is currently being investigated for the prevention of diaphragm atrophy in patients with mechanically supported breathing. Patients receiving breathing support from mechanical ventilation are at risk of mismatches between respiratory demand and ventilator support. Our objectives were to determine if a novel phrenic nerve stimulation device provided stimulation during inspiration as intended and did not exacerbate any potential discordances. A benchtop electromechanical simulation model was developed to validate phrenic nerve stimulation with simulated breathing. The phrenic nerve stimulation device was evaluated with a mechanical ventilator attached to a breathing simulator. The trigger ratio and time lag between phrenic nerve stimulation and mechanical ventilation was measured for multiple disease and ventilator parameters. For the 1:1 breath trigger ratio test, 99.79% of intended stimulation breaths received stimulation at the correct time. For the 1:4 breath trigger ratio test, 99.72% of intended stimulation breaths received stimulation at the correct time. For trigger lag times for the inspiratory and expiratory phases, the mean inspiratory lag was 36.10 ± 10.50 ms and 16.61 ± 3.61 ms, respectively. The following discordance scenarios were evaluated in conjunction with simulated phrenic nerve stimulation: asynchrony-false trigger, dyssynchrony-early trigger, dyssynchrony-late trigger, dyssynchrony-early cycling, dyssynchrony-late cycling. Testing demonstrated none of these discordances were exacerbated by the simulated phrenic nerve stimulation. The novel phrenic nerve stimulation device delivered electrical stimulation therapy as intended and did not exacerbate any simulated discordances.

ABSTRACT The COVID-19 pandemic has highlighted the critical need for accurate and efficient diagnostic tools for detecting severe acute respiratory coronavirus 2 (SARS-CoV-2) infections. This study presents a comparison of two diagnostic tests: RT-PCR and antigen detection rapid diagnostic tests (Ag-RDTs). This study focused on their performance, variant specificity, and their clinical implications. A simultaneous testing of 268 samples was carried out for SARS-CoV-2 using RT-PCR and Ag-RDTs [flourescence immunoassay (FIA) and lateral flow immunoassay (LFIA)]. Viral load was quantified, and variant identification was performed using a PCR-based assay. The prevalence was found to be 30.2% using reverse transcription PCR (RT-PCR), 26.5% using FIA, and 25% using LFIA. When comparing the FIA and LFIA, the overall diagnostic performance was found to be 80.25% vs 76.54%, 96.79% vs 97.33%, 91.55% vs 90.51%, and 91.88% vs 92.56% for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. Both Ag-RDTs showed a strong agreement with RT-PCR (κ = 0.78–0.80). The overall accuracies of the FIA and LFIA were 92.41% and 92.13%, respectively. The FIA showed higher sensitivity (73.68%) and PPV (92.08%) than the LFIA (65.79% and 90.56%, respectively) in asymptomatic patients. At low Ct values ( 30. The diagnostic sensitivity of FIA compared to LFIA for detecting the Alpha variant was 78.85% vs. 69.23% and 72.22% vs. 83.33% for the Delta variant. Both Ag-RDTs had 100% sensitivity for detecting Omicron. Both Ag-RDTs performed well in patients with high viral loads and Omicron variant infections compared to those infected with Alpha and Delta variants. This study confirms the comparable performance of RT-PCR and Ag-RDTs, specifically FIA and LFIA, for SARS-CoV-2 detection. The FIA showed higher sensitivity and PPV in asymptomatic cases, while both Ag-RDTs exhibited strong agreement with RT-PCR results. Notably, Ag-RDTs, particularly FIA, proved effective in detecting the Omicron variant and cases with high viral loads, highlighting their potential clinical utility in managing the COVID-19 pandemic.IMPORTANCEThis study is of utmost importance in providing effective responses to manage the COVID-19 pandemic. It rigorously compares the diagnostic accuracy, variant specificity, and practical considerations of reverse transcription PCR (RT-PCR) and antigen detection rapid diagnostic tests (Ag-RDTs) for severe acute respiratory coronavirus 2 (SARS-CoV-2), answering critical questions. The results of this study will help healthcare professionals choose the appropriate testing methods, allocate resources effectively, and enhance public health strategies. Given the evolution of the virus, understanding the performance of these diagnostic tools is crucial to adapting to emerging variants. Additionally, the study provides insights into logistical challenges and accessibility issues, which will contribute to refining testing workflows, particularly in resource-limited settings. Ultimately, the study’s impact extends to global healthcare, providing valuable information for policymakers, clinicians, and public health officials as they work together for mitigating the impact of the pandemic.

Abstract One fundamental principle that underlies various cancer treatments, such as traditional chemotherapy and radiotherapy, involves the induction of catastrophic DNA damage, leading to the apoptosis of cancer cells. In our study, we conduct a comprehensive dose-response combination screening focused on inhibitors that target key kinases involved in the DNA damage response (DDR): ATR, ATM, and DNA-PK. This screening involves 87 anti-cancer agents, including six DDR inhibitors, and encompasses 62 different cell lines spanning 12 types of tumors, resulting in a total of 17,912 combination treatment experiments. Within these combinations, we analyze the most effective and synergistic drug pairs across all tested cell lines, considering the variations among cancers originating from different tissues. Our analysis reveals inhibitors of five DDR-related pathways (DNA topoisomerase, PLK1 kinase, p53-inducible ribonucleotide reductase, PARP, and cell cycle checkpoint proteins) that exhibit strong combinatorial efficacy and synergy when used alongside ATM/ATR/DNA-PK inhibitors.

Abstract The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of California, Los Angeles (UCLA). The data collection includes elemental compositions of extraterrestrial materials analyzed by UCLA cosmochemists over the last five decades. The analytical techniques include atomic absorption spectrometry (AAS) and neutron activation analysis (NAA) at UCLA. The data collection is stored on the Astromaterials Data System (Astromat). We provide both interactive tables and downloadable datasheets for users to access all data. The UCLA Cosmochemistry Database archives cosmochemical data that are essential tools for increasing our understanding of the nature and origin of extraterrestrial materials. Future studies can reference the data collection in the examination, analysis, and classification of newly acquired extraterrestrial samples.

In this study, we aimed to characterize the affordance of interceptability for oneself using a manual lateral interception paradigm. We asked a two-fold research question: (1) What makes a virtual ball interceptable or not? (2) How reliably can individuals perceive this affordance for oneself? We hypothesized that a spatiotemporal boundary would determine the interceptability of a ball, and that individuals would be able to perceive this boundary and make accurate perceptual judgments regarding their own interceptability. To test our hypotheses, we administered a manual lateral interception task to 15 subjects. They were first trained on the task, which was followed by two experimental sessions: action and judging. In the former, participants were instructed to intercept as many virtual balls as possible using a hand-held slider to control an on-screen paddle. In the latter session, while making interceptions, participants were instructed to call “no” as soon as they perceived a ball to be uninterceptable. Using generalized linear modeling on the data, we found a handful of factors that best characterized the affordance of interceptability. As hypothesized, distance to be covered and ball flight time shaped the boundary between interceptable and uninterceptable balls. Surprisingly, the angle of approach of the ball also co-determined interceptability. Altogether, these variables characterized the actualized interceptability. Secondly, participants accurately perceived their own ability to intercept balls on over 75% of trials, thus supporting our hypothesis on perceived interceptability. Analyses revealed that participants considered this action boundary while making their perceptual judgments. Our results imply that the perceiving and actualizing of interceptability are characterized by a combination of the same set of variables.

Abstract Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non‐venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non‐venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA‐based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP‐based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non‐overlapping lineages, which was different from the mtDNA‐based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36–15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai‐Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

Advances in biomedical engineering continue to produce innovative wearable health sensors capable of real-time ambulatory assessments (e.g., of physiology, the environment), holding great potential for advancing precision monitoring and interventions through the integration of such devices and data into eHealth systems. As with any novel device, however, user views on acceptability and concerns about the technology must be evaluated to facilitate widespread implementation and user adoption of such devices. One factor that may strongly influence user views is the potential relevance to, and need for, self-care for chronic disease management. We examined if acceptability and concerns regarding innovative wearable devices differed between individuals living with or without chronic disease. A U.S. adult sample (N = 448; 20-70 yrs.; 34 % Female; 60 % White, 35 % Hispanic) completed a web-based survey regarding their thoughts/opinions related to innovative wearable sensors. Two-thirds (67 %, N = 298) reported at least one chronic disease; one-third (33 %, N = 150) reported no chronic health conditions. Participants viewed learning modules about two innovative devices: a watch to detect environmental gases for respiratory health, and a chest-patch monitoring real-time ECG. For each device, participants rated acceptability across multiple dimensions, and then rated potential concerns (including general concerns and specific worries about negative health impacts). Respondents with and without chronic disease differed in education, race, and ethnicity. Controlling for these differences, individuals with chronic disease reported significantly higher acceptability for the watch and for the chest-patch. Healthy participants reported significantly higher general concerns about technology. However, when concern questions were asked specifically about the potential negative impacts of the two study devices on physical health and well-being, participants with chronic disease reported significantly higher concerns. Overall, results show that living with chronic disease influences acceptability and concerns associated with adoption of innovative sensors. These findings suggest it is essential to take potential users' health status into account when studying the design and implementation of innovative wearable sensors. Dissemination strategies may benefit from emphasizing the beneficial features of these devices, addressing hesitations, and customizing implementation approaches by user group.

Aims: The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods: Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results: PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion: This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653.

Rapid and accurate detection of Klebsiella pneumoniae carbapenem resistance is important for infection control and targeted antibiotic therapy. PCR-based assay performance heavily depends on the quality and quantity of template DNA. Challenges arise from the necessity to isolate chromosomal and large plasmid-encoded resistance genes simultaneously from a limited number of target cells and to remove PCR inhibitors. qPCRs for the detection of K. pneumoniae strains carrying blaOXA-48, blaNDM-1, blaKPC-2, and blaVIM-1 carbapenemase genes were developed. We compared the performance of template DNA extracted with silica column-based methods, reversed elution systems, and lysis-only methods either from diluted culture fluid or from a synthetic stool matrix which contained PCR inhibitors typically present in stool. The synthetic stool matrix was chosen to mimic K. pneumoniae containing rectal swabs or stool samples in a reproducible manner. For total DNA isolated from culture fluid, resistance gene detection by qPCR was always possible, independent of the extraction method. However, when total DNA was isolated from synthetic stool matrix spiked with K. pneumoniae, most methods were insufficient. The best performance of template DNA was obtained with reversed elution. This highlights the importance of choosing the right DNA extraction method for consistent carbapenem resistance detection by PCR.

Abstract The prevalence of non-communicable diseases, such as diabetes and cardiovascular disease, is rising in low- and middle-income countries (LMICs). Health behavior change (HBC) interventions such as the widely used Diabetes Prevention Program (DPP) are effective at reducing chronic disease risk, but have not been adapted for LMICs. Leveraging mobile health (mHealth) technology such as text messaging (SMS) to enhance reach and participant engagement with these interventions has great promise, yet we lack evidence-informed approaches to guide the integration of SMS specifically to support HBC interventions in LMIC contexts. To address this gap, we integrated guidance from the mHealth literature with expertise and first-hand experience to establish specific development steps for building and implementing SMS systems to support HBC programming in LMICs. Specifically, we provide real-world examples of each development step by describing our experience in designing and delivering an SMS system to support a culturally-adapted DPP designed for delivery in South Africa. We outline eight key SMS development steps, including: 1) determining if SMS is appropriate; 2) developing system architecture and programming; 3) developing theory-based messages; 4) developing SMS technology; 5) addressing international SMS delivery; 6) testing; 7) system training and technical support; and 8) cost considerations. We discuss lessons learned and extractable principles that may be of use to other mHealth and HBC researchers working in similar LMIC contexts. Trial registration Clinicaltrials.gov, NCT03342274 . Registered 10 November 2017.

Abstract Small‐cell lung cancer (SCLC) is the most lethal type of lung cancer. Specifically, MYC‐driven non‐neuroendocrine SCLC is particularly resistant to standard therapies. Lurbinectedin was recently approved for the treatment of relapsed SCLC, but combinatorial approaches are needed to increase the depth and duration of responses to lurbinectedin. Using high‐throughput screens, we found inhibitors of ataxia telangiectasia mutated and rad3 related (ATR) as the most effective agents for augmenting lurbinectedin efficacy. First‐in‐class ATR inhibitor berzosertib synergized with lurbinectedin in multiple SCLC cell lines, organoid, and in vivo models. Mechanistically, ATR inhibition abrogated S‐phase arrest induced by lurbinectedin and forced cell cycle progression causing mitotic catastrophe and cell death. High CDKN1A/p21 expression was associated with decreased synergy due to G1 arrest, while increased levels of ERCC5/XPG were predictive of increased combination efficacy. Importantly, MYC‐driven non‐neuroendocrine tumors which are resistant to first‐line therapies show reduced CDKN1A/p21 expression and increased ERCC5/XPG indicating they are primed for response to lurbinectedin–berzosertib combination. The combination is being assessed in a clinical trial NCT04802174.

Previous research found that when participants across the lifespan could be the architect of their own stepping-stones landscapes, they create nonstandardized configurations with gap-width variation. Yet, architects often use standardized dimensions in their designs for playgrounds and outdoor fitness areas. To scrutinize why architects tend to seek for more standardized designs than the examined target users, we tested the hypothesis that the difference is caused by a different perspective during the making process. After all, landscape architects generally design on 2D maps, while the participants designed in situ. We asked 67 participants to design a stepping-stones landscape on a 2D map and 67 other participants to create the landscape in situ. Contrary to our expectations, we found no indications that designing on a 2D map leads to more standardized configurations. We end with discussing other characteristics of the design processes that could potentially explain the omnipresent standardization in design.

Traditional approaches for evaluating the impact of scientific research – mainly scholarship (i.e., publications, presentations) and grant funding – fail to capture the full extent of contributions that come from larger scientific initiatives. The Translational Science Benefits Model (TSBM) was developed to support more comprehensive evaluations of scientific endeavors, especially research designed to translate scientific discoveries into innovations in clinical or public health practice and policy-level changes. Here, we present the domains of the TSBM, including how it was expanded by researchers within the Implementation Science Centers in Cancer Control (ISC3) program supported by the National Cancer Institute. Next, we describe five studies supported by the Penn ISC3, each focused on testing implementation strategies informed by behavioral economics to reduce key practice gaps in the context of cancer care and identify how each study yields broader impacts consistent with TSBM domains. These indicators include Capacity Building, Methods Development (within the Implementation Field) and Rapid Cycle Approaches, implementing Software Technologies, and improving Health Care Delivery and Health Care Accessibility. The examples highlighted here can help guide other similar scientific initiatives to conceive and measure broader scientific impact to fully articulate the translation and effects of their work at the population level.

Introduction. Currently, sequencing has been the only tool for the identification of circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. However, it is known to be an expensive and laborious approach involving high technical expertise. Considering the reduced adherence to preventive measures postlockdown in Accra, this study presents an alternative method that leverages polymerase chain reaction (PCR) to identify circulating SARS-CoV-2 variants in the Accra Metropolis postlockdown. Methods. This prospective cross-sectional study was conducted between July and December 2022. Nasopharyngeal samples were collected from 268 consenting participants. Samples were subjected to nucleic acid extraction and followed by real-time polymerase chain reaction for the detection and quantification of SARS-CoV-2 RNA. SARS-CoV-2 positive samples were subsequently subjected to variant identification using rapid PCR. Findings. The prevalence of SARS-CoV-2 within the Accra Metropolis was 30.2%. The majority of the SARS-CoV-2 infection was diagnosed in females, participants aged 41–50 years, and symptomatic participants. Participants aged ≤10 years and females recorded the highest viral load while participants aged 41–50 years recorded the highest number of infections. The SARS-CoV-2 variants detected were Alpha (64.2%), Delta (22.2%), and Omicron (13.6%). Predictors of SARS-CoV-2 infection identified were chills, cough, headache, body weakness, sore throat, and dyspnoea in order of decreasing association with SARS-CoV-2 infection. There was a strong association between symptom status, gender, age, and SARS-CoV-2 infection. Conclusion. There was a high prevalence of SARS-CoV-2 within the Accra Metropolis postlockdown within the sampling period. The Alpha variant of SARS-CoV-2 is the predominant circulating variant, and persons presenting with symptoms are most likely to be diagnosed with COVID-19. Children aged ≤10 years serve as a reservoir for infection transmission.

In the current research we investigated how people deal with decisions in which they have to reject others, something that is unavoidably part of many selection procedures. Integrating insights derived from research on social exclusion and dehumanization, we argued that when people need to reject others, they dehumanize them. To study the association between dehumanization and rejecting in a real-life setting, we conducted two field studies, in which we examined the selection process in student houses, where residents can accept some prospective members, but have to reject others. As predicted, our findings showed that when people need to reject targets, they subtly dehumanize them. Moreover, dehumanizing rejected targets was related to lower rejection aversion. This suggests that when people dehumanize those they have to reject, rejection is easier.

Introduction: People with mental illness (MI) are more likely to smoke cigarettes and less likely to receive treatment for tobacco use than the general population. Understanding factors associated with improved staff treatment of tobacco use in community mental health settings has received limited study. Methods: We used data from a completed cluster-randomized clinical trial that tested two interventions designed to increase treatment for tobacco use in mental health clinics. Among 222 clinic staff, we examined demographic and employment characteristics, changes in perceived skills, knowledge, and beliefs using the S-KAP (i.e., perceptions of staff responsibility to treat tobacco use; client quit motivation; client outcomes; and barriers) as predictors of change in clinician reported delivery of tobacco use treatment following training. Results: Clinician reported treatment of client tobacco use significantly increased from baseline to week 52 across both study arms (p

Background Lifestyle Africa is an adapted version of the Diabetes Prevention Program designed for delivery by community health workers to socioeconomically disadvantaged populations in low- and middle-income countries (LMICs). Results from the Lifestyle Africa trial conducted in an under-resourced community in South Africa indicated that the programme had a significant effect on reducing haemoglobin A1c (HbA1c). Objective To estimate the cost of implementation and the cost-effectiveness (in cost per point reduction in HbA1c) of the Lifestyle Africa programme to inform decision-makers of the resources required and the value of this intervention. Methods Interviews were held with project administrators to identify the activities and resources required to implement the intervention. A direct-measure micro-costing approach was used to determine the number of units and unit cost for each resource. The incremental cost per one point improvement in HbA1c was calculated. Results The intervention equated to 71 United States dollars (USD) in implementation costs per participant and a 0.26 improvement in HbA1c per participant. Conclusions Lifestyle Africa reduced HbA1c for relatively little cost and holds promise for addressing chronic disease in LMIC. Decision-makers should consider the comparative clinical effectiveness and cost-effectiveness of this intervention when making resource allocation decisions. Trial Registration Trial registration is at ClinicalTrials.gov (NCT03342274).

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

Introduction Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes.Methods and analysis A total of 200 children aged 6–59 months with uncomplicated SAM (weight-for-height z-scores (WHZ)

Objective We assessed whether Water, Sanitation and Hygiene (WASH) and Infant and Young Child Feeding (IYCF), either alone or combined, were associated with malnutrition among Lao People’s Democratic Republic (Lao PDR) children aged 6 to

Abstract This study explored the informational variables guiding steering behaviour in a locomotor interception task with targets moving along circular trajectories. Using a new method of analysis focussing on the temporal co-evolution of steering behaviour and the potential information sources driving it, we set out to invalidate reliance on plausible informational candidates. Applied to individual trials rather than ensemble averages, this Qualitative Inconsistency Detection (QuID) method revealed that steering behaviour was not compatible with reliance on information grounded in any type of change in the agent-centred target-heading angle. First-order changes in the environment-centred target’s bearing angle could also not adequately account for the variations in behaviour observed under the different experimental conditions. Capturing the observed timing of unfolding steering behaviour ultimately required a combination of (velocity-based) first-order and (acceleration-based) second-order changes in bearing angle. While this result may point to reliance on fractional-order based changes in bearing angle, the overall importance of the present findings resides in the demonstration of the necessity to break away from the existing practice of trying to fit behaviour into a priori postulated functional strategies based on categorical differences between operative heuristic rules or control laws.

Abstract Chiral materials, similarly to human hands, have distinguishable right-handed and left-handed enantiomers which may behave differently in response to external stimuli. Here, we use for the first time an approach based on the density functional theory (DFT)+PAOFLOW calculations to quantitatively estimate the so-called collinear Rashba–Edelstein effect (REE) that generates spin accumulation parallel to charge current and can manifest as chirality-dependent charge-to-spin conversion in chiral crystals. Importantly, we reveal that the spin accumulation induced in the bulk by an electric current is intrinsically protected by the quasi-persistent spin helix arising from the crystal symmetries present in chiral systems with the Weyl spin–orbit coupling. In contrast to conventional REE, spin transport can be preserved over large distances, in agreement with the recent observations for some chiral materials. This allows, for example, the generation of spin currents from spin accumulation, opening novel routes for the design of solid-state spintronics devices.

Abstract Worldwide, over 250 million children under 5 years do not reach their developmental potential due to several causes, including malnutrition. In Cambodia, the prevalence of stunting and wasting among children remains high. This prospective cohort study aimed to assess acquisition of motor and cognitive developmental milestones in early childhood and their associations with stunting and wasting. Children aged from 0 to 24 months were recruited from three provinces in Cambodia and followed up to seven times from March 2016 to June 2019, until their 5 years. Data collection included anthropometry and developmental milestones. Seven motor and seven cognitive milestones were evaluated using the Cambodian Development Milestone Assessment Tool. Associations were assessed with parametric survival models. Hazard ratios (HR) below 1 stood for lower probabilities for achieving developmental milestones. Data were available for 7394 children. At 12 months, the prevalence of stunting and wasting were 23.7% and 9.6% respectively. Both were consistently associated with delays in most motor and cognitive milestones. Stunting was strongly associated with delays in gross motor milestones (HR

Abstract Speciation rates vary substantially across the tree of life. These rates should be linked to the rate at which population structure forms if a continuum between micro and macroevolutionary patterns exists. Previous studies examining the link between speciation rates and the degree of population formation in clades have been shown to be either correlated or uncorrelated depending on the group, but no study has yet examined the relationship between speciation rates and population structure in a young group that is constrained spatially to a single‐island system. We examine this correlation in 109 gemsnakes (Pseudoxyrhophiidae) endemic to Madagascar and originating in the early Miocene, which helps control for extinction variation across time and space. We find no relationship between rates of speciation and the formation rates of population structure over space in 33 species of gemsnakes. Rates of speciation show low variation, yet population structure varies widely across species, indicating that speciation rates and population structure are disconnected. We suspect this is largely due to the persistence of some lineages not susceptible to extinction. Importantly, we discuss how delimiting populations versus species may contribute to problems understanding the continuum between shallow and deep evolutionary processes.

Abstract Food taboos encompass food restrictions practiced by a group that go beyond individual preferences. During pregnancy and lactation, food taboos may contribute to inadequate nutrition and poor maternal and infant health. Restriction of specific fish, meat, fruits and vegetables is common among peripartum women in many Southeast Asian countries, but data from Cambodia are lacking. In this mixed‐methods study, 335 Cambodian mothers were asked open‐ended questions regarding dietary behaviours during pregnancy and up to 24 weeks postpartum. Descriptive statistics and content analysis were used to characterize food taboos and multiple logistic regression analyses were conducted to identify predictors of this practice. Participants were 18–44 years of age, all of Khmer ethnicity and 31% were primiparous. Sixty‐six per cent of women followed food taboos during the first 2 weeks postpartum, whereas ~20% of women restricted foods during other peripartum periods. Pregnancy taboos were often beneficial, including avoidance of sugar‐sweetened beverages, coffee and alcohol. Conversely, postpartum avoidances typically included nutrient‐dense foods such as fish, raw vegetables and chicken. Food taboos were generally followed to support maternal and child health. No significant predictors of food taboos during pregnancy were identified. Postpartum, each additional live birth a woman had reduced her odds of following food taboos by 24% (odds ratio [95% confidence interval]: 0.76 [0.61–0.95]). Specific food taboo practices and rationales varied greatly between women, suggesting that food taboos are shaped less by a strict belief system within the Khmer culture and more by individual or household understandings of food and health during pregnancy and postpartum.

Abstract Information on fortifiable food consumption is essential to design, monitor and evaluate fortification programmes, yet detailed methods like 24‐h recalls (24HRs) that provide such data are rarely conducted. Simplified questionnaire‐based methods exist but their validity compared with 24HRs has not been shown. We compared two simplified methods (i.e., a household food acquisition and purchase questionnaire [FAPQ] and a 7‐day semiquantitative food frequency questionnaire [SQ‐FFQ]) against 24HRs for estimating fortifiable food consumption. We assessed the consumption of fortifiable wheat flour and oil using a FAPQ and, for wheat flour only, a 7‐day SQ‐FFQ and compared the results against 24HRs. The participants included children 12−18 months (n = 123) and their mothers 18−49 years selected for a study assessing child vitamin A intake and status in Mandaluyong City, Philippines. For fortifiable wheat flour, the FAPQ estimated considerably lower mean intakes compared to 24HRs for children and mothers (2.2 vs. 14.1 g/day and 5.1 vs. 42.3 g/day, respectively), while the SQ‐FFQ estimated slightly higher mean intakes (15.7 vs. 14.1 g/day and 51.5 vs. 42.3 g/day, respectively). For fortifiable oil, the FAPQ estimated considerably higher mean intakes compared to 24HRs for children and mothers (4.6 vs. 1.8 g/day and 12.5 vs. 6.1 g/day, respectively). The SQ‐FFQ, but not the FAPQ, generated useful information on fortifiable food consumption that can inform fortification programme design and monitoring decisions in the absence of more detailed individual‐level data. Potential adaptations to improve the FAPQ, such as additional questions on foods prepared away from home and usage patterns, merit further research.

Commercial tree plantations of fast-growing species have become increasingly important in Southeast Asia to meet global demand for wood and wood fiber products. There is a growing need to understand more about their value for wildlife and how they can be managed for biodiversity. We evaluated the effects of landscape attributes on mammal communities in a timber concession consisting of 83 % secondary forest and 17 % tree plantations in northern Sabah, Malaysia. Using camera traps, we compared mammalian species assemblages of secondary forest and commercial tree plantation stands and identified habitat predictors associated with total mammal species detections and species richness in the landscape mosaic. We used 87 camera stations deployed for 23 days across two major land-use types: 62 sites in secondary forest (previously logged natural forest) and 25 sites in tree plantations. We evaluated variation in species richness in these two major land-use categories and assessed the effects of natural and anthropogenic predictors on variation in total mammal detections and species richness. We detected at least 23 large and medium-sized mammal species over 2035 trap nights. Fourteen of those species were classified as threatened or near-threatened by the International Union for the Conservation of Nature. Rarefaction did not reveal differences in mammal species richness or diversity between camera sites placed in tree plantations and secondary forests, likely because most camera sites in tree plantations were close to secondary forest and comprised

There is still considerable debate on the exact composition of grains formed in the outflows of O-rich, asymptotic giant branch stars. Estimates of the expected condensation distances based on radiative transfer calculations show that iron-free silicates can condense close to the star but typically lack the opacity to drive an outflow unless they are large enough that radiation pressure due to scattering on the grains becomes significant. Iron-containing silicates have a much higher absorption opacity, but due to this stronger absorption, their expected condensation location is well beyond the expected dust formation zone. Recent measurements of the efficiency of SiO condensational growth have shown that this rate is low. The result of this low growth efficiency is that nucleation may persist for longer, giving a larger number of smaller primary particles, leading to an increased likelihood of particle aggregation in these outflows. In this work, we examine how the radiation pressure changes with the possible aggregation of these primary particles into fractal aggregates. Opacity calculations are made using optical properties of both forsterite and astronomical silicate for aggregates containing up to 256 primary particles and for fractal dimensions of 1.8 and 2.8. For primary particles of radius less than ∼0.1 μ m, aggregation leads to an enhancement of the radiation pressure over an equivalent cloud of isolated primary particles.

Omar Moussa,1 Tahvi Frank,2 Ives A Valenzuela,1 Joah Aliancy,1 Dan Gong,3 Joaquin O De Rojas,4 Lora R Dagi Glass,1 Bryan J Winn,5 George A Cioffi,1 Royce WS Chen1 1Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA; 2Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; 3Department of Ophthalmology, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; 4Center for Sight, Sarasota, FL, USA; 5Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USACorrespondence: Royce WS Chen, Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, 635 W. 165th St, New York, NY, 10032, USA, Tel +1 212-305-9535, Email rc2631@cumc.columbia.eduPurpose: To evaluate efficacy of a novel risk stratification system in minimizing resident surgical complications and to evaluate whether the system could be used to safely introduce cataract surgery to earlier levels of training.Materials and Methods: This is a retrospective cross-sectional study on 530 non-consecutive cataract cases performed by residents at Columbia University. Risk scores, preoperative best corrected visual acuity (BCVA), intraoperative complications, postoperative day 1 (POD1), and month 1 (POM1) exam findings were tabulated. The relationship between risk scores and POD1 and POM1 BCVA was modeled using linear regression. The relationship between risk scores and complication rates was modeled using logistic regression. Logistic regression was used to model the rates of complications across different levels of training. Rates of complications were compared between diabetic versus non-diabetic patients using t-tests.Results: Risk scores did not have significant association with intraoperative complications. Risk scores were predictive of corneal edema (OR = 1.36, p = 0.0032) and having any POM1 complication (OR = 1.20, p = 0.034). Risk scores were predictive of POD1 (β = 0.13, p < 0.0001) and POM1 (β = 0.057, p = 0.00048) visual acuity. There was no significant association between level of training and rates of intraoperative (p = 0.9) or postoperative complications (p = 0.06). Rates of intraoperative complication trended higher among diabetic patients but was not statistically significant (p = 0.2).Conclusion: Higher risk scores were predictive of prolonged corneal edema but not risk of intraoperative complications. Our risk stratification system allowed us to safely introduce earlier phacoemulsification surgery.Keywords: cataract, cataract risk stratification, resident phacoemulsification surgery

Abstract Frontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices at an early age of onset. The disorder shows considerable clinical, pathological, and genetic heterogeneity. Here we investigated the proteomic signatures of frontal and temporal cortex from brains with frontotemporal dementia due to GRN and MAPT mutations to identify the key cell types and molecular pathways in their pathophysiology. We compared patients with mutations in the GRN gene (n = 9) or with mutations in the MAPT gene (n = 13) with non-demented controls (n = 11). Using quantitative proteomic analysis on laser-dissected tissues we identified brain region-specific protein signatures for both genetic subtypes. Using published single cell RNA expression data resources we deduced the involvement of major brain cell types in driving these different protein signatures. Subsequent gene ontology analysis identified distinct genetic subtype- and cell type-specific biological processes. For the GRN subtype, we observed a distinct role for immune processes related to endothelial cells and for mitochondrial dysregulation in neurons. For the MAPT subtype, we observed distinct involvement of dysregulated RNA processing, oligodendrocyte dysfunction, and axonal impairments. Comparison with an in-house protein signature of Alzheimer’s disease brains indicated that the observed alterations in RNA processing and oligodendrocyte function are distinct for the frontotemporal dementia MAPT subtype. Taken together, our results indicate the involvement of different brain cell types and biological mechanisms in genetic subtypes of frontotemporal dementia. Furthermore, we demonstrate that comparison of proteomic profiles of different disease entities can separate general neurodegenerative processes from disease-specific pathways, which may aid the development of disease subtype-specific treatment strategies.

Abstract We estimated how micronutrient needs of young children, aged 6–24 months were covered by the standard (traditional) diets in Ghana and Benin, and the contributions of partial breastfeeding and national nutrition programs aimed at improving micronutrient status to overall micronutrient intakes. Estimates of micronutrient intake from standard diets were based on previous surveys, using the food composition table of West Africa (INFOOD). Recommended micronutrient intakes were based on World Health Organization recommendations. Children were grouped in three age groups (6–8, 9–12, and 13–24 months) to capture the changing dynamics of the complementary feeding period. As expected, from 6 months of age onwards, breastmilk didn't cover the micronutrient needs. The standard diets contributed only minimal to micronutrient intakes of children ranging from 0% to 37% of recommended intakes for Ca, Fe, Zn, vitamin A, vitamin D and iodine depending on the micronutrient considered. The contribution of mass (bio)‐fortification programs to the coverage of micronutrient needs varied widely, depending on the staple food considered and the country, but overall did not allow to fill the gap in micronutrient needs of children except for vitamin A in some contexts. In contrast, consumption of voluntary fortified complementary food, especially formulated for the needs in this age groups, contributed substantially to overall micronutrient intake and could fill the gap for several micronutrients. The development of young child‐targeted programs including micronutrient‐dense foods, associated with interventions to increase the diet diversity and meal frequency, could significantly improve micronutrients intakes of children in both Ghana and Benin.

Study region: The Southern Hills aquifer system (SHAS) in the Louisiana Capital Area Groundwater Conservation District (CAGCD), USA. Study focus: The SHAS provides abundant groundwater for public and industrial supplies in the CAGCD. Groundwater depletion, saltwater intrusion, and land subsidence are potential concerns due to prolonged excessive groundwater withdrawals. This study develops a high-fidelity groundwater flow model utilizing a complex unstructured grid to investigate groundwater flow and storage responses to excessive groundwater withdrawals for the SHAS in the CAGCD. The groundwater model incorporates the Mississippi River alluvial aquifer down to the Miocene sands extending to depths around 1 km. New hydrological insights: Groundwater modeling results indicate large cones of depression in the Evangeline and Jasper formations in the Baton Rouge area due to prolonged groundwater withdrawals. Low-permeability faults are inferred by significant groundwater level difference across the faults. While local groundwater storage depletion in deeper aquifers is evident, overall estimated groundwater storage changes of the SHAS in the CAGCD are close to zero in the past two decades, indicating insignificant groundwater storage changes. This is attributed to dominant interactions between the major rivers and the shallower alluvial aquifer. In addition, the simulated groundwater storage changes exhibit patterns similar to those derived by the Gravity Recovery and Climate Experiment (GRACE) model that has been used in evaluation of groundwater depletion in many regional studies.

Abstract Despite substantial efforts to control locusts they remain periodically a major burden in Africa, causing severe yield loss and hence loss of food and income. Distribution maps indicating the value of the basic reproduction number R 0 was used to identify areas where an insect pest can be controlled by a natural enemy. A dynamic process-based mathematical model integrating essential features of a natural enemy and its interaction with the pest is used to generate R 0 risk maps for insect pest outbreaks, using desert locust and the entomopathogenic fungus Metarhizium acridum (Synn. Metarhizium anisoliae var. acridum) as a case study. This approach provides a tool for evaluating the impact of climatic variables such as temperature and relative humidity and mapping spatial variability on the efficacy of M. acridum as a biocontrol agent against desert locust invasion in Africa. Applications of M. acridum against desert locust in a few selected African countries including Morocco, Kenya, Mali, and Mauritania through monthly spatial projection of R 0 maps for the prevailing climatic condition are illustrated. By combining mathematical modeling with a geographic information system in a spatiotemporal projection as we do in this study, the field implementation of microbial control against locust in an integrated pest management system may be improved. Finally, the practical utility of this model provides insights that may improve the timing of pesticide application in a selected area where efficacy is highly expected.

Background: In Lao PDR, acute malnutrition remains a public health problem, with around 9% of children under 5 being affected. Outpatient treatment of severe acute malnutrition requires ready-to-use therapeutic foods (RUTFs), but concerns have been raised about the acceptability of globally available products. Culturally acceptable RUTFs could be locally developed, but data are lacking on RUTF preferences in Lao PDR. Methods: In a crossover-designed study, four different RUTFs were tested for short-term acceptability and organoleptic qualities (two globally available: peanut-based, which is the current standard, and wheat–milk-based RUTFs; two regionally produced: a mung-bean-based and a fish–rice-based RUTF). Organoleptic properties were evaluated by 83 caretaker–child pair participants through a taste test and a 30 min consumption test. Short-term acceptability was assessed through a 3-day intake test. The study sites were in Phongsaly (North Laos) and Attapeu (South Laos). Focus group discussions were conducted at the beginning and the end of the study. Results: The mung bean RUTF was the favorite among caretakers, with an acceptability percentage of 96.2%, and scored better (p-value < 0.05) for all organoleptic variables than the other three RUTFs. Overall, 3 days after receiving take-home rations, the mean percentage of consumption was above 80% for all the RUTFs, with the mung bean product being the most consumed. Conclusions: The regionally produced mung bean RUTF was the most accepted, whereas the other regionally produced fish-based RUTF was the least accepted, showing the complexity of finding culturally acceptable solutions to fight malnutrition. For Lao PDR, a mung-bean-based RUTF seems the way forward, even if the current standard peanut-based RUTF appeared to be acceptable, albeit not the most preferred.

Abstract Background Microscopic examination of human blood samples is an excellent opportunity to assess general health status and diagnose diseases. Conventional blood tests are performed in medical laboratories by specialized professionals and are time and labor intensive. The development of a point-of-care system based on a mobile microscope and powerful algorithms would be beneficial for providing care directly at the patient's bedside. For this purpose human blood samples were visualized using a low-cost mobile microscope, an ocular camera and a smartphone. Training and optimisation of different deep learning methods for instance segmentation are used to detect and count the different blood cells. The accuracy of the results is assessed using quantitative and qualitative evaluation standards. Results Instance segmentation models such as Mask R-CNN, Mask Scoring R-CNN, D2Det and YOLACT were trained and optimised for the detection and classification of all blood cell types. These networks were not designed to detect very small objects in large numbers, so extensive modifications were necessary. Thus, segmentation of all blood cell types and their classification was feasible with great accuracy: qualitatively evaluated, mean average precision of 0.57 and mean average recall of 0.61 are achieved for all blood cell types. Quantitatively, 93% of ground truth blood cells can be detected. Conclusions Mobile blood testing as a point-of-care system can be performed with diagnostic accuracy using deep learning methods. In the future, this application could enable very fast, cheap, location- and knowledge-independent patient care.

The tropical montane cloud forests (TMCF) of the Talamanca Mountains of Costa Rica are a unique and understudied habitat that is home to a high number of endemic bird species. Cloudbridge Nature Reserve is a TMCF reforestation reserve lying on the Pacific slope of Cerro Chirripó in the cantón of Pérez Zeledón. Here, we synthesize data collected at Cloudbridge between March 2016 and May 2020 from multi-year point count, walking, call-playback, and camera trap surveys along with photographs collected from February 2007 to April 2021 to present a bird species inventory of the reserve. In total, 204 bird species from 40 families, including 40 endemic species, were identified, and monthly presence summarized for each species. We discuss the implications of our findings for understanding TMCF avian communities, as well as the importance of year-round surveys using a variety of techniques to better capture overall avian diversity.

Metastatic clear cell renal cell carcinomas (ccRCCs) are resistant to DNA-damaging chemotherapies, limiting therapeutic options for patients whose tumors are resistant to tyrosine kinase inhibitors and/or immune checkpoint therapies. Here we show that mouse and human ccRCCs were frequently characterized by high levels of endogenous DNA damage and that cultured ccRCC cells exhibited intact cellular responses to chemotherapy-induced DNA damage. We identify that pharmacological inhibition of the DNA damage–sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) with the orally administered, potent, and selective drug M4344 (gartisertib) induced antiproliferative effects in ccRCC cells. This effect was due to replication stress and accumulation of DNA damage in S phase. In some cells, DNA damage persisted into subsequent G2/M and G1 phases, leading to the frequent accumulation of micronuclei. Daily single-agent treatment with M4344 inhibited the growth of ccRCC xenograft tumors. M4344 synergized with chemotherapeutic drugs including cisplatin and carboplatin and the poly(ADP-ribose) polymerase inhibitor olaparib in mouse and human ccRCC cells. Weekly M4344 plus cisplatin treatment showed therapeutic synergy in ccRCC xenografts and was efficacious in an autochthonous mouse ccRCC model. These studies identify ATR inhibition as a potential novel therapeutic option for ccRCC.