bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Health Work and Social Work Collaboration: Integration in Health Care and Public Health Settings
Authors: Petruzzi Liana , Smithwick Julie , Lee Lily , Delva Jorge , Fox Lillie , Wilkinson Geoff , Vohra-Gupta Shetal , Aranda Maria , Valdez Carmen , Jones Barbara
Published: May 2024

Community health worker (CHW) and social worker (SW) collaboration is crucial to illness prevention and intervention, yet systems often engage the 2 workforces in silos and miss opportunities for cross-sector alignment. In 2021, a national workgroup of over 2 dozen CHWs, SWs, and public health experts convened to improve CHW/SW collaboration and integration across the United States. The workgroup developed a conceptual framework that describes structural, systemic, and organizational factors that influence CHW/SW collaboration. Best practices include standardized training, delineated roles and scopes of practice, clear workflows, regular communication, a shared system for documentation, and ongoing support or supervision.
Utility of scores to predict alcohol use after liver transplant: Take them with a grain of salt
Authors: Houston Kevin , Duong Nikki , Sterling Richard K. , Asgharpour Amon , Bullock Sheila , Weinland Stephan , Keller Nicole , Smirnova Ekaterina , Khan Hiba , Matherly Scott , Wedd Joel , Lee Hannah , Siddiqui Mohammad , Patel Vaishali , Arias Albert , Kumaran Vinay , Lee Seung , Sharma Amit , Khan Aamir , Imai Daisuke , Levy Marlon , Bruno David
Published: May 2024

The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. After LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol testing. Patients with alcohol-associated liver disease were stratified by < or > 6 months of sobriety before listing. Those with <6 months were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was the utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict a return to alcohol use (+phosphatidylethanol) within 1 year after LT. Of the 365 LT, 86 had > 6 months of sobriety, and 85 had <6 months of sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, the return to drinking was similar in the AH (24%) compared to <6-month non-AH (15%) and >6-month alcohol-associated liver disease (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict a return to alcohol was low (accuracy 61%–63%) with poor sensitivity (46% and 37%), specificity (67%–68%), positive predictive value (22%–26%) with moderate negative predictive value (81%–83%), respectively with higher negative predictive values (95%) in predicting a return to heavy drinking. Both SALT and HRAR scores had good negative predictive value in identifying patients at low risk for recidivism.
Antenatal Care: A Comparative Review of Guidelines
Authors: Boureka Eirini , Tsakiridis Ioannis , Kostakis Nikolaos , Giouleka Sonia , Mamopoulos Apostolos , Kalogiannidis Ioannis , Athanasiadis Apostolos , Dagklis Themistoklis
Published: May 2024

Importance

Antenatal care plays a crucial role in safely monitoring and ensuring the well-being of both the mother and the fetus during pregnancy, ultimately leading to the best possible perinatal outcomes.

Objective

The aim of this study was to review and compare the most recently published guidelines on antenatal care.

Evidence Acquisition

A descriptive review of guidelines from the National Institute for Health and Care Excellence, the Public Health Agency of Canada, the World Health Organization, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists regarding antenatal care was conducted.

Results

There is a consensus among the reviewed guidelines regarding the necessary appointments during the antenatal period, the proper timing for induction of labor, the number and frequency of laboratory examinations for the assessment of mother's well-being, and management strategies for common physiological problems during pregnancy, such as nausea and vomiting, heartburn, pelvic pain, leg cramps, and symptomatic vaginal discharge. In addition, special consideration should be given for mental health issues and timely referral to a specialist, reassurance of complete maternal vaccination, counseling for safe use of medical agents, and advice for cessation of substance, alcohol, and tobacco use during pregnancy. Controversy surrounds clinical evaluation during the antenatal period, particularly when it comes to the routine use of an oral glucose tolerance test and symphysis-fundal height measurement for assessing fetal growth, whereas routine cardiotocography and fetal movement counting are suggested practices only by Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Of note, recommendations on nutritional interventions and supplementation are offered only by Public Health Agency of Canada and World Health Organization, with some minor discrepancies in the optimal dosage.

Conclusions

Antenatal care remains a critical factor in achieving positive outcomes, but there are variations depending on the socioeconomic status of each country. Therefore, the establishment of consistent international protocols for optimal antenatal care is of utmost importance. This can help provide safe guidance for healthcare providers and, consequently, improve both maternal and fetal outcomes.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the learner should be better able to describe appropriate laboratory and clinical assessment plans during the antenatal period; identify common physiological problems of pregnancy and propose appropriate management strategies; and evaluate the recommended supplementation and nutritional interventions during pregnancy.
The BRAF V600E Mutation and Clinicopathological Changes Among Patients With Hashimoto Thyroiditis, Papillary Thyroid Carcinoma With Hashimoto Thyroiditis, and Nodular Goiter
Authors: Deng Juqing , Yu Lu , Luo Shibi , Yang Zhongcun , Liu Jie , Liao Liqiong
Published: May 2024

The study aimed to investigate the BRAF V600E mutation and clinicopathological changes among patients with Hashimoto thyroiditis (HT), papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT), or nodular goiter (NG). A total of 87 patients with the BRAF V600E mutation who were diagnosed with HT (including with hyperplasia dysplasia), PTC with HT, and PTC with NG were enrolled. Clinical data, concentrations of antithyroglobulin antibodies (TGAb) and thyroid microsomal antibodies (TMAb) in the serum thyroid-function levels, and the result presence of the BRAF V600E mutation were retrospectively analyzed. There were significant differences in the BRAF V600E mutation rates between the HT and PTC with HT groups (P<0.05) and the HT and PTC with NG groups (P<0.05), whereas no significant difference was found between the PTC with HT and PTC with NG groups. There was no difference in incidences of PTC between HT with elevated TGAb and TMAb group and those with baseline levels. The incidence of multifocal PTC was higher in the PTC with HT group; however, the difference was not significant. Our findings documented that BRAF mutation distinguished between the benign HT and the malignant PTC groups. The serum levels of TGAb and TMAb autoantibodies did not directly correlate with PTC in the background of HT. HT and NG may similarly contribute to the pathogenesis of PTC.
The Psychology of Patients With Oral-Facial Clefts: A Review of Victor Hugo’s The Man Who Laughs (L’homme qui rit)
Authors: Jung Sung Gyun , Hwang Kun , Hwang Young Joong
Published: May 2024

In Victor Hugo’s The Man Who Laughs, the protagonist has a facial cleft. The authors aimed to comprehend the psychological experience of a patient with a facial cleft by analyzing this novel. The novel concerns the life of a young nobleman, Gwynplaine, disfigured as a child, who travels with his protector and companion, the vagabond philosopher Ursus, and Dea, a baby girl he rescued. During the oppressive rule of the king, one of his adversaries was Lord Linnaeus Clancharlie, who had taken refuge in Switzerland. The tyrannical monarch ordered the execution of Gwynplaine’s father and commissioned a surgeon, Dr Hardquannone, to carve the boy’s face into a perpetual grin. The king declared that he should “laugh forever at his fool of a father.” Subsequently, the king sold the boy to a group who specialized in the mutilation and disfigurement of children. On the psychology of a boy with an appearance giving the impression of laughing, Hugo wrote: “By laughing Gwynplaine made people laugh. However, he wasn’t laughing. His face laughed, his thoughts did not.” When Ursus met Gwynplaine, Ursus asked the boy: “What are you laughing at?” The boy replied: I’m not laughing. Ursus: Then you are terrible. Gwynplaine’s unnatural laughter, which stems from an artificial deformation of the muscles, is a silent form of laughter. It represents the eternal laughter of those who do not truly laugh, signifying emotional emptiness and an accompanying sense of indifference. Plastic surgeons can restore an “unnatural laughing face” to a “natural smiling face.”
A diadectid skin impression and its implications for the evolutionary origin of epidermal scales
Authors: Voigt Sebastian , Calábková Gabriela , Ploch Izabela , Nosek Vojtěch , Pawlak Wojciech , Raczyński Paweł , Spindler Frederik , Werneburg Ralf
Published: May 2024

Corneous skin appendages are not only common and diverse in crown-group amniotes but also present in some modern amphibians. This raises the still unresolved question of whether the ability to form corneous skin appendages is an apomorphy of a common ancestor of amphibians and amniotes or evolved independently in both groups. So far, there is no palaeontological contribution to the issue owing to the lack of keratin soft tissue preservation in Palaeozoic anamniotes. New data are provided by a recently discovered ichnofossil specimen from the early Permian of Poland that shows monospecific tetrapod footprints associated with a partial scaly body impression. The traces can be unambiguously attributed to diadectids and are interpreted as the globally first evidence of horned scales in tetrapods close to the origin of amniotes. Taking hitherto little-noticed scaly skin impressions of lepospondyl stem amniotes from the early Permian of Germany into account, the possibility has to be considered that the evolutionary origin of epidermal scales deeply roots among anamniotes.
The cells of Robert Hooke: wombs, brains and ammonites
Authors: Peters Winfried S.
Published: May 2024

Robert Hooke (1635–1703) is commonly credited for introducing the term cell into biology when describing the microscopic structure of plant tissues in his
Micrographia
of 1665. This narrative ignores that, at the time, cell was an established term denoting linearly arranged elements of structures with functions in the storage, modification and transport of materials (e.g. the uterus, colon, brain, etc.). In analogy to the cells of these organs, Hooke interpreted plant cells as elements of continuous tubes for the storage and regulated movement of vital fluids. Hooke also was one of the few British natural philosophers who regarded ‘serpentine-stones’, the fossilized chambered shells of cephalopods (e.g. ammonites) that seemed to lack living counterparts, as remnants of organisms. He considered
Nautilus
a living serpentine-stone and referred to the chambers in its shell as cells, postulating that gas and liquid were transported along and stored within these cavities for buoyancy regulation. Hooke published this theory in 1696, but probably developed it much earlier. In
Micrographia
, he described ammonite cells just before plant cells, suggesting an overlooked rhetoric function of his report of cells in plants. By visualizing microscopic equivalents of macroscopic cellular structures for the first time, Hooke reinforced the common notion that living matter generally was characterized by such structures. Consequently, the presence of cells in serpentine-stones implicitly supported his organismic interpretation of these fossils.
How networks shape diversity for better or worse
Authors: Musso Andrea , Helbing Dirk
Published: May 2024

Socio-diversity, the variety of human opinions, ideas, behaviours and styles, has profound implications for social systems. While it fuels innovation, productivity and collective intelligence, it can also complicate communication and erode trust. So what mechanisms can influence it? This paper studies how fundamental characteristics of social networks can support or hinder socio-diversity. It employs models of cultural evolution, mathematical analysis and numerical simulations. We find that pronounced inequalities in the distribution of connections obstruct socio-diversity. By contrast, the prevalence of close-knit communities, a scarcity of long-range connections, and a significant tie density tend to promote it. These results open new perspectives for understanding how to change social networks to sustain more socio-diversity and, thereby, societal innovation, collective intelligence and productivity.
Disentangling the within- and between-person effects of personality on income for men and women
Authors: Kemp Simon , Yogeeswaran Kumar , Stronge Samantha , Yaghoubi Mona , Sibley Chris G.
Published: May 2024

Understanding the relationship between personality and income is a topic of interest across multiple disciplines. Correlations between people’s personalities and their incomes may arise because differences in stable personalities relate to income differences (between-person effects) or because changes in personality or income are later reflected in the other variable (within-person effects). The current research uses random-intercept cross-lagged panel models to disentangle the two sorts of effects to better understand the relationship between the six factors of personality and income. Using data from 6824 working-age adults in New Zealand across 4 years, we found between-person effects showing higher incomes were obtained by both men and women who were more extraverted, agreeable and open, and less neurotic. Within-person effects showed that earning a higher income was associated with higher neuroticism and lower extraversion over time, while higher extraversion was associated with a lower income over time.
Little evidence that androstadienone affects social distance-dependent prosocial behaviour: a pre-registered study
Authors: Lu Junsong , Ye Yuting , Wu Yin
Published: May 2024

In navigating the complexities of social life, humans have evolved to interpret invisible odorous chemical cues, with profound behavioural impacts often unbeknown to the conscious mind. The manifestation of this in humans is evident in the scent of androstadienone (androsta-4,16-dien-3-one), an odorous compound which is considered a putative human pheromone. The current study investigated the effect of androstadienone on social distance-dependent prosocial behaviour measured by a social discounting task, in which participants chose between selfish and generous options. Based on our pre-registration, we predicted a sex-specific effect, with males exposed to androstadienone exhibiting increased generosity, while females would choose more selfishly. Employing a double-blind, placebo-controlled, between-subject design, we recruited 170 participants who were randomly assigned to either the androstadienone or control condition. Olfactory stimuli were administered while participants completed the social discounting task. Inconsistent with our hypothesis, inhaling androstadienone did not impact social distance-dependent prosocial behaviour. This finding was supported by multiple estimates of prosociality, including model-free, model-based and maximum likelihood estimation. Further analyses indicated that androstadienone administration did not influence perceived social distance or bias participants towards being generous or selfish. Thus, our empirical findings provide no support for the hypothesis that androstadienone modulates generosity.
The commoditization of civil nuclear power
Authors: Patterson Eann A. , Taylor Richard J.
Published: May 2024

The commoditization of nuclear power through the factory production of sealed micro-power units within a digitally enabled holistic assurance framework is described. This would revolutionize nuclear power-plant design, construction, operation and decommissioning through a paradigm shift to manufacture–operate–remove–recycle (MORR). The potential impact of recent research on an integrated nuclear digital environment for large bespoke nuclear power plants and the design, build and operation of fusion power plants using such a digital environment is explored. These strands are interwoven to discuss the technical, economic and socio-political implications of MORR in the context of micro-reactors and to consider the potential evolution of safeguarding issues based on a digital assurance framework that leads to type approvals. Commoditization of nuclear power would lower costs in line with offshore wind and the output from a single production line in a factory could replace a third of current fossil fuel-based electricity generation in the UK over a 15-year period, making a significant contribution to achieving zero greenhouse gas emissions. The challenges associated with the changes in culture, both in the nuclear industry and in society, as well as the technology gaps, that need to be addressed in realizing this paradigm shift are identified and discussed.
Investigating the impact of anthropogenic noise on the decision-making of dwarf mongoose offspring
Authors: Vane Lauren S. , Morris-Drake Amy , Arbon Josh J. , Thomson Robyn J. , Layton Megan , Kern Julie M. , Radford Andrew N.
Published: May 2024

Anthropogenic (man-made) noise constitutes a novel and widespread pollutant which is increasing in prevalence in terrestrial and aquatic ecosystems, resulting in alterations of natural soundscapes. There is proliferating evidence that noise leads to maladaptive behaviour in wildlife, yet few studies have addressed the effect on mammalian parent–offspring interactions. We investigated the impact of road noise on dwarf mongoose (
Helogale parvula
) offspring nearest-neighbour decision-making while foraging, using a field-based playback experiment. We predicted that offspring would forage closer to groupmates, especially adult and dominant individuals, when experiencing road noise compared with ambient sound to reduce communication masking and alleviate stress. We also predicted that noise would have a reduced effect with increasing offspring age owing to reduced reliance on adult groupmates for provisioning and predator defence. However, we found that mean nearest-neighbour distance and nearest-neighbour intrinsic characteristics (age, sex and dominance status) did not differ significantly between sound treatments, and these responses did not vary significantly with focal individual age. Noise may not impact nearest-neighbour decision-making owing to habituation from chronic natural exposure; alternatively, noise could induce stress and distraction, resulting in maladaptive decision-making. Future work should aim to detangle the underlying mechanisms mediating parent–offspring interactions in conditions of anthropogenic noise.
Immune Infiltration and Survival Analysis in Lung Adenocarcinoma: Identifying Prognostic Cell Types
Authors: Verma Madhulika
Published: May 2024

The tumor microenvironment (TME) plays a crucial role in the development and survival of neoplastic cells, with tumor-infiltrating leukocytes (TILs) constituting a significant component. This immune infiltrate exhibits a diverse composition of adaptive and innate immunological cell subtypes, with varying prognostic implications across different cancer types. Recent advancements in immunotherapy underscore the importance of evaluating TILs as potential biological identifiers, particularly in the context of novel treatment strategies. In lung adenocarcinoma, the most prevalent histological subtype of lung cancer, multiple immune cell types have been identified within the TME, influencing tumor classification, clinical outcomes, and patient survival. While prior research has demonstrated a correlation between tumor-infiltrating immune cells and the progression of lung adenocarcinoma, few studies have examined their prognostic implications comprehensively.

Building upon our previous work, where we constructed a signature matrix (Verma, 2024b.) and evaluated the fractions of 14 immune cell types in TCGA-LUAD data and performed ESTIMATE analysis to assess immune infiltration, stromal infiltration, and tumor purity (Verma, 2024a.), in this study, we investigate the association between immune cell infiltration patterns and the overall survival and prognosis of TCGA-LUAD patients across different histological subtypes and stages. Our findings aim to elucidate the immune cell types positively or negatively impacting patient outcomes in lung adenocarcinoma and inform future therapeutic approaches.
Analytical platform to validate microRNA biomarkers for cancer or disease with practically 100% sensitivity and specificity
Authors: Kanavarioti Anastassia , Rehman M. Hassaan , Qureshi Salma , Rafiq Aleena , Sultan Madiha
Published: May 2024

We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate, or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma‒Aldrich #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex, and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p value of 1.6×10-22, tentatively validating each miRNA as a cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer.
A Novel Multi-strain Vaginal Synbiotic is Effective in Optimizing the Vaginal Microbiome: Results from a Randomized, Placebo-controlled Clinical Trial
Authors: Ravel Jacques , Greenwood Jaswa Eleni , Gottfried Sara , Greene Miriam , Kellogg-Spadt Susan , Gevers Dirk , Harper Diane
Published: May 2024

This research letter describes the results of a clinical trial of a novel vaginal synbiotic comprising threeL. crispatusstrains and a supportive nutrient complex. Results indicated that administration of the synbiotic led to an optimal vaginal microbiome dominated byL. crispatus(CST I) and additionally reduced the abundance of microbes associated with vaginal dysbiosis and the abundance ofCandida, the most common source of vaginal yeast infections.
A Natural History Study of Timothy Syndrome
Authors: Timothy Katherine W. , Bauer Rosemary , Larkin Kerry A. , Walsh Edward P. , Abrams Dominic J. , Corcia Cecilia Gonzalez , Valsamakis Alexandra , Pitt Geoffrey S. , Dick Ivy E. , Golden Andy
Published: May 2024

Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the geneCACNA1C. Timothy syndrome patients were first identified as having a cardiac presentation of Long QT and syndactyly of the fingers and/or toes, and an identical variant inCACNA1C, Gly406Arg. However, since this original identification, more individuals harboring diverse variants inCACNA1Chave been identified and have presented with various cardiac and extra-cardiac symptoms. Furthermore, it has remained underexplored whether individuals harboring canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) have additional symptoms. Here, we describe the first Natural History Study for Timothy syndrome, providing a thorough resource describing the current understanding of disease manifestation in Timothy syndrome patients. Parents of Timothy syndrome children were queried regarding a wide-ranging set of symptoms and features via a survey. Importantly, we find that in addition to cardiac concerns, Timothy syndrome patients commonly share extra-cardiac features including neurodevelopmental impairments, hypoglycemia, and respiratory problems. Our work expands the current understanding of the disorder to better inform the care of Timothy syndrome patients.
ROLE OF cfDNA AND ctDNA TO IMPROVE THE RISK STRATIFICATION AND THE DISEASE FOLLOW-UP IN PATIENTS WITH ENDOMETRIAL CANCER: TOWARDS THE CLINICAL APPLICATION
Authors: Casas-Arozamena Carlos , Vilar Ana , Cueva Juan , Arias Efigenia , Sampayo Victoria , Diaz Eva , Oltra Sara S , Moiola Cristian Pablo , Cabrera Silvia , Cortegoso Alexandra , Curiel Teresa , Abalo Alicia , Serrano Mónica Pamies , Domingo del Pozo Santiago , Padilla-Iserte Pablo , Arnaez de la Cruz Marta , Hernández Alicia , García-Pineda Virginia , Ruiz Bañobre Juan , López Rafael , Matias-Guiu Xavier , Colás Eva , Gil-Moreno Antonio , Abal Miguel , Moreno-Bueno Gema , Muinelo-Romay Laura
Published: May 2024

Introduction

In the past years, there has been a rise on advanced endometrial cancers (EC) patients resulting in mortality increase. To overcome this trend, it is essential to improve the stratification of the risk of post-surgery recurrence and to anticipate the development of disease relapse and resistance to treatment. Liquid biopsy analyses represent a promising tool to address these clinical challenges, however, the best strategy to efficiently apply them in the context of EC must be better defined. Therefore, the study was designed to determine the value of cfDNA/ctDNA monitoring to improve the clinical management of patients with localized and recurrent disease.

Material & Methods

Plasma samples and the uterine aspirate (UA) from 198 patients with EC were collected in different Spanish hospitals at surgery and throughout the course of the disease. The genetic landscape of UAs was characterized using targeted sequencing. Total cfDNA was isolated from all plasma samples, quantified, and analysed for the presence of ctDNA based on the mutational profile found on the UAs.

Results

The genetic characterization of UAs obtained at surgery allowed the identification of pathogenetic variants in the 95,45% of the tumours and ctDNA levels could be monitored in the 89,4% of the patients. High levels of cfDNA and detectable levels of ctDNA at baseline correlated with poor prognosis, for both DFS (p-value<0.0001; HR=9,25) and DSS (p-value<0.0001; HR=11,20). Importantly, this approach remains clinically significant when stratifying tumours based on histopathological risk factors, highlighting its additional value to identify patient with a poor evolution. In fact, cfDNA/ctDNA analysis served to identify patients who showed early post-surgery relapse. Moreover, longitudinal analyses of cfDNA/ctDNA proved to be a powerful asset to identify patients undergoing relapse, months prior to the arisen of any clinical evidence.

Conclusion

This study represents the most comprehensive study on cfDNA/ctDNA characterization in EC and demonstrates its value to improve the risk stratification and anticipate the disease relapse in patients with localized disease. Besides, the dynamic ctDNA assessment showed utility to complement the current strategies to monitor disease evolution and the response to treatment. Implementation of cfDNA/ctDNA monitoring into the clinical routine will provide an unique opportunity to improve EC management.

GRAPHICAL ABSTRACT
X-COVNet: Externally Validated Model for Computer-Aided Diagnosis of Pneumonia-Like Lung Diseases in Chest X-Rays Based on Deep Transfer Learning
Authors: Pazos Jorge Félix Martínez , Gonzales Jorge Gulín , Lorenzo David Batard , García Arturo Orellana
Published: May 2024

Since the appearance of COVID-19, the accurate diagnosis of pneumonia-type lung diseases by chest radiographs has been a challenging task for experts, mainly due to the similarity of patterns between COVID-19 and viral or bacterial pneumonia. To address this challenge, a model for the computer-aided diagnosis of chest X-Rays has been developed in this research. This model might contribute to substantially increasing the accuracy of the diagnosis. This approach is based on supervised learning using neural networks, where the quality of the result depends on the quality of the dataset used during training. Image data augmentation techniques, hyperparameter adjustments and dropout layer contributed to achieve high performance values on test data in multi-class classification. The experiments conducted to evaluate the model yielded that it detects and classifies domain classes with an accuracy of 99.45% on training data, 99.27% on validation data and 99.06% on selected test data. The main contribution of this paper is X-COVNet a new Deep Convolutional Neural Network model using Deep Transfer Learning through the Xception architecture for the assisted diagnosis of COVID-19, pneumonia or healthy patients, trained on COVID-19 Chest X-Ray Database and evaluated through two external databases, which give the model novelty within the lack of external validation in all the literature reviewed.
Mortality Classification for Deaths that Follow the Use of Non-Firearm Force by Police: A National Cross-Sectional Study (United States, 2012-2021)
Authors: Feldman Justin M. , Lloyd Tracey , Solomon Phillip Atiba
Published: May 2024

Background

Mortality classification for deaths in US police custody has important consequences for epidemiologic monitoring and legal outcomes. Prior literature suggests in-custody death classification is inconsistent and may not reflect non-firearm force that preceded death.

Methods

We analyzed the Associated Press “Lethal Restraint” national dataset (United States, 2012-2021; N = 1,036), which included deaths following police use of non-firearm force. Our primary outcomes included whether the death investigator: (1) classified manner of death as a homicide, (2) mentioned a force-related injury/condition in the cause-of-death statement, and (3) mentioned any force. Inverse-probability-weighted logistic models estimated the association of these outcomes with death-investigator jurisdiction type, local political composition (quartile of Republican Party vote %), decedent race/ethnicity, and each agency’s prior classifications.

Findings

We removed 96 deaths based on exclusion criteria. Of the remaining 940 deaths, 28.5% were classified as homicide, 16.5% had cause-of-death statements mentioning a force-related injury/condition, and 42.6% mentioned any force. In contrast, 73.9% of statements mentioned drugs. Unadjusted results showed homicide classification increased from 25.0% in 2012-2014 to 32.2% in 2018-2021. Models estimating adjusted prevalence differences (aPD) showed that, compared to medical examiner jurisdictions, coroners (aPD: -0.19; 95% CI: -0.31, - 0.06) and sheriff-coroners (a PD: -0.17; 95% CI: -0.28, -0.05) were less likely to classify deaths as homicides. Model results also showed that classifications for incidents occurring in the least-Republican counties were most likely to reflect force across all three manner and cause outcomes.

Interpretation

Non-homicide classifications and cause-of-death statements making no mention of force were widespread for US in-custody deaths. We identified novel evidence suggesting coroner and sheriff-coroner jurisdictions were especially unlikely to categorize in-custody deaths as homicides, and that incidents occurring in highly Republican counties were least likely to reflect force in the cause or manner of death.

Funding

Blue Meridian Partners Justice and Mobility Fund
Single-cell and spatiotemporal profile of ovulation in the mouse ovary
Authors: Huang Ruixu , Kratka Caroline Elisabeth , Pea Jeffrey , McCann Cai , Nelson Jack , Bryan John P. , Zhou Luhan Tracy , Russo Daniela D. , Zaniker Emily J. , Gandhi Achla H. , Shalek Alex K. , Cleary Brian , Farhi Samouil L. , Duncan Francesca E. , Goods Brittany A.
Published: May 2024

Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.
Are Genomic Language Models All You Need? Exploring Genomic Language Models on Protein Downstream Tasks
Authors: Boshar Sam , Trop Evan , de Almeida Bernardo P. , Copoiu Liviu , Pierrot Thomas
Published: May 2024

Large language models, trained on enormous corpora of biological sequences, are state-of-the-art for downstream genomic and proteomic tasks. Since the genome contains the information to encode all proteins, genomic language models (gLMs) hold the potential to make downstream predictions not only about DNA sequences, but also about proteins. However, the performance of gLMs on protein tasks remains unknown, due to few tasks pairing proteins with the coding DNA sequences (CDS) that can be processed by gLMs. In this work, we curated five such datasets and used them to evaluate the performance of gLMs and proteomic language models (pLMs). We show that gLMs are competitive and even outperform their pLMs counterparts on some tasks. The best performance was achieved using the retrieved CDS compared to sampling strategies. We found that training a joint genomic-proteomic model outperforms each individual approach, showing that they capture different but complementary sequence representations, as we demonstrate through model interpretation of their embeddings. Lastly, we explored different genomic tokenization schemes to improve downstream protein performance. We trained a new Nucleotide Transformer (50M) foundation model with 3mer tokenization that outperforms its 6mer counterpart on protein tasks while maintaining performance on genomics tasks. The application of gLMs to proteomics offers the potential to leverage rich CDS data, and in the spirit of the central dogma, the possibility of a unified and synergistic approach to genomics and proteomics. We make our inference code, model weights and datasets available.
Genome Report: A chromosome-level genome assembly of the varied leaved jewelflower,Streptanthus diversifolius,reveals a recent whole genome duplication
Authors: Davis John T. , Li Qionghou , Grassa Christopher J. , Davis Matthew , Strauss Sharon Y. , Gremer Jennifer R. , Rieseberg Loren H. , Maloof Julin N.
Published: May 2024

The Streptanthoid complex, a clade of primarilyStreptanthusandCaulanthusgenera in the Thelypodieae tribe (Brassicaceae) is an emerging model system for ecological and evolutionary studies. This Complex spans the full range of the California Floristic Province including desert, foothill, and mountain environments. The ability of these related species to radiate into dramatically different environments makes them a desirable study subject for exploring how plant species expand their ranges and adapt to new environments over time. Ecological and evolutionary studies for this complex have revealed fascinating variation in serpentine soil adaptation, defense compounds, germination, flowering, and life history strategies. Until now a lack of available genomic resources has hindered the ability to relate these phenotypic observations to their underlying genetic and molecular mechanisms. To help remedy this situation we present here a chromosome-level genome assembly ofStreptanthus diversifolius, a member of the Streptanthoid Complex, developed using Illumina, Hi-C, and HiFi sequencing technologies. Construction of this assembly also provides further evidence to support the previously reported recent whole genome duplication unique to the Thelypodieae tribe. This whole genome duplication may have provided individuals in the Streptanthoid Complex the genetic arsenal to rapidly radiate throughout the California Floristic Province and to occupy commonly inhospitable environments including serpentine soils.
Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation
Authors: Soria Erika , Lu Qiusheng , Boswell Will , Du Kang , Xing Yanting , Boswell Mikki , Weldon Korri S , Lai Zhao , Savage Markita , Schartl Manfred , Lu Yuan
Published: May 2024

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between divergedXiphophorusspecies showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certainXiphophorusspecies do not develop such tumors. Here we report the identification of a locus residing in the genome of oneXiphophorusspecies that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility.

Significance

The Dobzhansky–Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky–Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.
CountASAP: A Lightweight, Easy to Use Python Package for Processing ASAPseq Data
Authors: Boughter Christopher T. , Chatterjee Budhaditya , Ohta Yuko , Gorga Katrina , Blair Carly , Hill Elizabeth M. , Fasana Zachary , Adebamowo Adedola , Ammar Farah , Kosik Ivan , Murugan Vel , Chen Wilbur H. , Singh Nevil J. , Meier-Schellersheim Martin
Published: May 2024

Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. To address this, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences.
Melanin-concentrating hormone promotes feeding through the lateral septum
Authors: Payant Mikayla A. , Shankhatheertha Anjali , Chee Melissa J.
Published: May 2024

Feeding is necessary for survival but can be hindered by anxiety or fear, thus neural systems that can regulate anxiety states are key to elucidating the expression of food-related behaviors. Melanin-concentrating hormone (MCH) is a neuropeptide produced in the lateral hypothalamus that promotes feeding and anxiogenesis. The orexigenic actions of MCH that prolong ongoing homeostatic or hedonic feeding are context-dependent and more prominent in male than female rodents, but it is not clear where MCH acts to initiate feeding. The lateral septum (LS) promotes feeding and suppresses anxiogenesis when inhibited, and it comprises the densest projections from MCH neurons. However, it is not known whether the LS is a major contributor to MCH-mediated feeding. As MCH inhibits LS cells by MCH receptor (MCHR1) activation, MCH may promote feeding via the LS. We bilaterally infused MCH into the LS and found that MCH elicited a rapid and long-lasting increase in the consumption of standard chow and a palatable, high sugar diet in male and female mice; these MCH effects were blocked by the co-administration of a MCHR1 antagonist TC-MCH 7c. Interestingly, the orexigenic effect of MCH was abolished in a novel, anxiogenic environment even when presented with a food reward, but MCH did not induce anxiety-like behaviors. These findings indicated the LS as a novel region underlying orexigenic MCH actions, which stimulated and enhanced feeding in both sexes in a context -dependent manner that was most prominent in the homecage.
Epileptic encephalopathy linked to a DALRD3 missense variant impaired in tRNA modification function
Authors: Zhang Kejia , Löhner Katharina , Lemmink Henny H. , Boon Maartje , Lentini Jenna M. , de Silva Naduni , Fu Dragony
Published: May 2024

Epileptic encephalopathies are severe epilepsy syndromes characterized by early onset and progressive cerebral dysfunction. A nonsense variant in theDALR Anticodon Binding Domain Containing 3(DALRD3) gene has been implicated in epileptic encephalopathy but no other disease-associated variants inDALRD3have been described. In human cells, the DALRD3 protein forms a complex with the METTL2 methyltransferase to generate the 3-methylcytosine (m3C) modification in specific arginine tRNAs. Here, we identify a patient with a homozygous missense variant in DALRD3 who displays developmental delay, cognitive deficiencies, and multifocal epilepsy. The missense variant substitutes an arginine residue to cysteine (R517C) within the DALR domain of DALRD3 that is required for binding tRNAs. Patient cells homozygous for the DALRD3-R517C variant exhibit reduced levels of m3C modification in arginine tRNAs, indicating that the R517C variant impairs DALRD3 function. Notably, the DALRD3-R517C variant displays reduced association with METTL2 and loss of interaction with substrate tRNAs. Our results uncover a novel pathogenic variant in DALRD3 that links DALRD3 loss-of-function to epileptic encephalopathy disorders. Importantly, these findings underscore DALRD3-dependent tRNA modification as a key contributor to proper brain development and function.
Kinetical analysis of D-alanine upon oral intake in humans
Authors: Kimura Tomonori , Sakai Shinsuke , Horio Masaru , Takahara Shiro , Ishigo Shoto , Nakane Maiko , Negishi Eiichi , Imoto Hiroshi , Mita Masashi , Hamase Kenji , Higa-Maekawa Yoko , Kakuta Yoichi , Mizui Masayuki , Isaka Yoshitaka
Published: May 2024

D-Alanine, a rare enantiomer of alanine in life, can potentially alleviate the worsening of viral infections and maintain circadian rhythm. This study aimed to analyze the kinetics of D-alanine upon oral intake. Five healthy volunteers were administered D-alanine as a single oral dose at 12,366 or 33,708 μmoL. Upon intake of the lower dose, the plasma level of D-alanine reached its peak concentration of 588.4 ± 40.9 μM with a peak time of 0.60 ± 0.06 h. The plasma level of D-alanine became close to the endogenous level after 24 h. The compartment model estimated the clearance of D-alanine at 12.5 ± 0.3 L/h, or 208 ± 5 mL/min, distribution volume of 8.3 ± 0.7 L and half-life of 0.46 ± 0.04 h. The peak concentration and area under the curve increased proportionally upon intake of the higher dose, while the clearance, distribution volume and half-life did not. The urinary ratio of D-alanine reached its peak of nearly 100%, followed by a slow decline. The peak time of the urinary ratio was 1.15 ± 0.15 h, showing a time lag of blood to urine excretion. Fractional excretion of D-alanine increased from 14.0 ± 5.8% to 64.5 ± 10.3%; the latter corresponded to the urinary clearance of D-alanine as about 77 mL/min for an adult, with a peak time of 1.90 ± 0.56 h. D-Alanine was quickly absorbed and appeared in blood, followed by urinary excretion. This kinetic analysis increases our fundamental knowledge of the oral intake of D-alanine.
Simultaneous assessment of genetic and epigenetic contributions to plasma lipid levels with respect to cardiovascular risk
Authors: Takeuchi Fumihiko , Yamamoto Masaya , Nakatochi Masahiro , Takano Kozue , Okazaki Atsuko , Emoto Sakurako , Tabara Yasuharu , Katsuya Tomohiro , Yamamoto Ken , Isono Masato , Mori Kotaro , Matsubara Tatsuaki , Ichihara Sahoko , Yokota Mitsuhiro , Hara Hisao , Hiroi Yukio , Kato Norihiro
Published: May 2024

Background

This study aims to develop a model for simultaneously assessing genetic and epigenetic contributions to plasma lipid levels.

Methods

The predictive model was developed using two cardiovascular risk groups, i.e., individuals with high low-density lipoprotein cholesterol (LDL-C) levels (≥160 mg/dl,N= 296) and coronary artery disease (CAD) (N= 315), in contrast to reference (maxN= 3,801) and non-CAD individuals (N= 164). For genetic predisposition, rare pathological variants in five target genes related to familial hypercholesterolemia (FH) were screened, while common variants were characterized to calculate a polygenic risk score (PRS). The methylation risk score (MRS) was also calculated for epigenetic profiles based on DNA methylation levels at 13 CpG sites. A relationship between these variables and lipid levels was analyzed in regression and quantile models.

Results

A total of 17 rare FH-related gene variants were identified in patients with high LDL-C or CAD, significantly more prevalent than in the general Japanese population (2.8% vs. 0.2%,P<1×10−15). For the rare variants plus PRS, the predictability of individual LDL-C increased (correlation coefficient between predicted and measured values,r= 0.261,P= 1.7×10−11) compared to PRS alone (r= 0.151,P= 1.2×10−4). PRS and MRS had the most significant impact on high-density lipoprotein cholesterol and triglycerides, respectively. The two risk scores had additive effects on these traits.

Conclusions

Our results provide proof-of-concept that assessing the relative contribution of genetic predisposition and DNA methylation levels (reflecting past environmental exposures) may help individuals refine their dyslipidemia treatment.