bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive brain stimulation over the Frontopolar Cortex promotes willingness to exert cognitive effort in a foraging-like sequential choice task
Authors: Bogdanov Mario , Bustamante Laura A. , Devine Sean , Sheldon Signy , Otto A. Ross
Published: October 2024

Individuals avoid spending cognitive effort unless expected rewards offset the perceived costs. Recent work employing tasks that provide explicit information about demands and incentives, suggests causal involvement of the Frontopolar Cortex (FPC) in effort-based decision-making. Using transcranial direct current stimulation (tDCS), we examined whether the FPC’s role in motivating effort generalizes to sequential choice problems in which task demand and reward rates vary indirectly and as a function of experience. In a double-blind, within- subject design, 46 participants received anodal (i.e., excitatory) or sham stimulation over the right FPC during an Effort Foraging Task, which required choosing between harvesting patches for successively decreasing resources or traveling to replenished patches by performing a cognitive task with environment-specific difficulty. As expected, participants exited patches later (i.e., displayed lower exit thresholds) when travelling required greater (versus less) effort, indicating increased travel costs in high-effort environments. Under anodal tDCS, the difference in exit thresholds between environments was significantly smaller relative to sham. Finally, individual differences analyses hint that participants with lower self-reported motivation to exert effort exhibited greater travel cost reductions following tDCS. Together, these findings support the theorized causal role of the FPC in motivating cognitively effortful behavior, expand its role to more ecologically valid serial decisions and highlight the potential for tDCS as a tool to increase motivation with potential clinical applications.

Significance statement

Uncovering the neural mechanisms regulating engagement in effortful behavior is crucial, as it will improve our understanding and treatment of conditions characterized by reduced motivation, e.g., apathy and anhedonia. The Frontopolar Cortex (FPC) has been implicated in increasing effort exertion in settings that provide explicit information about effort demand and reward. Using transcranial direct current stimulation (tDCS), we investigated whether the FPC retains its motivating capacity in sequential choice problems that vary effort and reward indirectly. We demonstrate that FPC stimulation decreases cognitive effort-based travel costs in an Effort Foraging Task, indicating a causal and general involvement of the FPC in motivating effortful behavior, highlighting the potential of tDCS as a new avenue for increasing motivation with potential clinical applications.
Restoration of Fbxo7 expression in dopaminergic neurons restores tyrosine hydroxylase in a mouse model of Parkinson’s disease
Authors: Al Rawi Sara , Tyers Pamela , Barker Roger A , Laman Heike
Published: October 2024

Mutations inFBXO7are linked to an atypical parkinsonism. Conditional knock out (KO) of Fbxo7 in dopaminergic neurons in a mouse model caused a neurodegenerative phenotype, including a significant reduction in striatal TH staining at 6 weeks of age and a significant loss of dopaminergic neurons in the SNpc. To test whether re-expression of Fbxo7 could act as a treatment to prevent or restore TH expression in the striatum in this model, we used a rAAV vector to deliver murine Fbxo7 and a mRuby fluorescent marker to dopaminergic neurons. We found that Fbxo7 expression, both before and after the TH loss, restored its expression in the striatum and nucleus accumbens in the mouse. This study therefore highlights that Fbxo7 is important for the integrity and persistence of the dopaminergic nigrostriatal pathway in the mammalian brain, which could be of relevance to Parkinson’s disease with therapeutic implications.
Early hominin arrival in Southeast Asia triggered the evolution of major human malaria vectors
Authors: Singh Upasana Shyamsunder , Harbach Ralph E. , Hii Jeffery , Chang Moh Seng , Somboon Pradya , Prakash Anil , Sarma Devojit , Broomfield Ben , Morgan Katy , Albert Sandra , Das Aparup , Linton Yvonne-Marie , Carlton Jane M. , Walton Catherine
Published: October 2024

Understanding the evolution of anthropophily, the preference of mosquitoes to feed on humans, offers insights into current and future human disease transmission. Some species of the Leucosphyrus Group ofAnophelesmosquitoes in Southeast Asia are highly anthropophilic and efficient vectors of human malaria parasites, while others primarily feed on non-human primates and transmit non-human primate malaria parasites. Through phylogenomic analysis of 11 out of 20 recognized species, we studied the biogeography and evolutionary history of anthropophily in this group. Molecular dating and ancestral state reconstruction revealed that anthropophily evolved during the late Pliocene/early Pleistocene in Sundaland, likely in response to early hominins. This finding provides independent non-archaeological evidence supporting the limited fossil record of early hominin colonization in Southeast Asia around 1.8 million years ago.
Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors
Authors: Dreyer Kathleen S. , Donahue Patrick S. , Boucher Jonathan D. , Chambers Katherine M. , Ornelas Marya Y. , Edelstein Hailey I. , Leibowitz Benjamin D. , Zhu Katherine J. , Dray Kate E. , Muldoon Joseph J. , Leonard Joshua N.
Published: October 2024

DNA-based hypoxia biosensors conditionally express a gene of interest when a cell is in a state of inadequate oxygen supply, which is a feature of several acute and chronic diseases. These biosensors can be deployed in engineered cells to study or treat disease. Although the central mediators of hypoxia responsiveness have been characterized, the dynamics of this response are generally less understood, and there is no general approach to modulate hypoxia biosensors to tune their performance to meet application-specific needs. To address the need for high-performing hypoxia biosensors, we investigated strategies to enhance biosensor performance by identifying minimal promoter choices and positive feedback circuits that both achieved low background and amplified hypoxia-induced gene expression. To generate insight into the mechanisms by which feedback drives differential performance, we developed an explanatory mathematical model. Our analysis suggests a previously unreported dual regulatory mechanism that was necessary to explain the full set of experimental observations and that provides new insights into regulatory dynamics in chronic hypoxia. This study exemplifies the potential of using synthetic gene circuits to perturb natural systems in a manner that uniquely enables the elucidation of novel facets of natural regulation.
The dynamics of wildVitisspecies in response to climate change facilitate the breeding of grapevine and its rootstocks with climate resilience
Authors: Zhang Mengyan , Xu Xiaodong , Zhang Tianhao , Liu Zhenya , Wang Xingyi , Shi Xiaoya , Peng Wenjing , Wang Xu , Chen Zhuyifu , Zhao Ruoyan , Wang Wenrui , Zhang Yi , Jin Zhongxin , Zhou Yongfeng , Ma Zhiyao
Published: October 2024

Climate change poses significant challenges to agricultural suitability and food security due to the limited adaptability of domesticated crops, however, our understanding of their climate adaptability is still limited. In this study, we compare the potential distributional dynamics in response to future climate change between grapevine and its wild relatives (VitisL.) based on ecological niche models (ENMs). We reveal that the annual mean temperature is the primary factor influencing the potential distribution of cultivated grapes (V. viniferaL.). By 2080, under RCP 8.5, suitable areas for wine and table grapes fromV. viniferaare predicted to reduced by 15.04×105km² and 13.26×105km², respectively. The results suggest that grape cultivation, particularly for table grapes, will face serious threats from future climate change. In contrast, seventy percent of wild grapes are well able to withstand future climate conditions. For example, under RCP 8.5, North American wild grapes likeV. rotundifoliaandV. labrusca, as well as East Asian wild grapes such asV. heyneanaandV. davidii, are projected to demonstrate significant adaptability. These wild grapes have the potential to provide rootstocks that could enhance the adaptability of cultivated grapes and serve as invaluable resources for breeding programs aimed at developing new cultivars better suited to withstand the environmental pressures of climate change. Our results not only predict potential suitable distribution areas of wild grapes in the future, but also emphasize the essential impact of these wild genetic resources on grape breeding for promoting adaptation to future climate change.
Understanding Thromboembolus Transport Patterns In The Brain For Stroke In The Presence Of Carotid Artery Stenosis
Authors: Roopnarinesingh Ricardo , Jani Neel D. , Leppert Michelle , Mukherjee Debanjan
Published: October 2024

Deciphering the source of an embolism is a common challenge encountered in stroke treatment. Carotid stenosis is a key source of embolic strokes. Carotid interventions can be indicated when a patient has greater than 50% stenosis in the carotid ipsilateral to the cerebral infarction, which is designated as the symptomatic carotid. However, there are often significant number of cases where carotid emboli travel contralaterally leading to ambiguity regarding which carotid is symptomatic. We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 30 heart-to-brain arterial models with differing combinations of bilateral severe and mild stenosis degrees. We used these models to study source-to-destination transport of thromboemboli released from left/right carotid disease sites, and cardiogenic sources. Across all cases considered, thromboemboli from left and right carotid sources showed non-zero contralateral transport. We also found that cardiogenic thromboemboli do not have an altered hemisphere distribution or distinct transport preference dependent on stenosis degree, thus potentially making the underlying etiology more cryptic. In patients with carotid stenosis or chronic occlusion ipsilateral to the area affected by stroke, we have demonstrated that the presence of contralateral stenosis can cause emboli that travel across the Circle of Willis (CoW) which can potentially lead to ambiguity when deciding which carotid is truly symptomatic.
The international trial of nasal oxygen therapy after cardiac surgery (NOTACS) in patients at high risk of postoperative pulmonary complications: Economic evaluation protocol and analysis plan
Authors: Shetty Siddesh , Duckworth Melissa , Norman Richard , Affandi Jacquita , Dawson Sarah , Fox-Rushby Julia
Published: October 2024

Introduction

High-Flow Nasal Therapy (HFNT) is an innovative non-invasive form of respiratory support. Compared to standard oxygen therapy (SOT), there is an equipoise regarding the effect of HFNT on patient-centred outcomes among those at high risk of developing postoperative pulmonary complications after undergoing cardiac surgery. The NOTACS trial aims to determine the clinical and cost-effectiveness of HFNT compared to SOT within 90 days of surgery in the United Kingdom, Australia, and New Zealand. This protocol describes the methods and analyses planned for economic evaluation embedded within the ongoing NOTACS trial.

Methods and analysis

The economic evaluation will identify, measure and value resources and health outcomes in both trial arms and compare changes in costs with ‘days alive and at home’ and EQ-5D-5L quality adjusted life years (QALYs) from the perspective most relevant to the decision-making country. Results from pooling data across the trial will use health and social care sector perspective. All patient-specific data including hospital/community care and health outcomes will be collected prospectively. Unit costs will be sourced interpreted using recommended national cost-effectiveness thresholds.

Registration details

The study is registered with ISRCTN (ISRCTN14092678) on 13/05/2020. ISRCTN is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set.
Determining the indirect costs of suicide in Sweden between 2010 and 2019 - A cost of illness study
Authors: Wikström Daniela , Nystrand Camilla , Hadlaczky Gergö , Gedin Filip
Published: October 2024

Background

Globally, more than 700 thousand people commit suicide annually. In Sweden, the yearly incidence is between 1000 and 1500 people, which is higher than the global average. Understanding the economic burden of suicide could help highlight the importance and urgency of finding more effective treatments and preventative measures to help people suffering from suicidal thoughts and support studies evaluating the cost-effectiveness of various interventions.

Method

This national population-based cross-sectional study estimated the indirect costs associated with all suicides in Sweden between 2010 and 2019. Indirect costs were estimated using the human capital approach. Data regarding average salaries and employment rates were extracted from publicly available data in Sweden. Productivity loss was estimated over two time horizons, the year following the suicide and over a lifetime horizon. Estimations were performed in total numbers for the yearly cohorts as well as per person.

Results

Between 2010 and 2019, 1 406 to 1 591 suicides occurred every year in Sweden. In total, approximately 26 500 productive life years are lost every year due to suicide. In 2019, the productivity loss due to all suicides in Sweden was estimated to be 44 million euros over a one-year time horizon, where 10 million euros are direct losses in local and regional authority taxes. Over a lifetime, productivity losses amounted to 935 million euros. The corresponding estimations per person were 37 and 778 thousand euros respectively over a one-year and a lifetime time horizon Over a one-year time horizon, the productivity loss was highest in the older age groups.

Conclusions

This study provides valuable insights into the economic burden of suicide on Swedish society. It underlines the potential economic benefits of effective suicide prevention, aligning with previous research highlighting the substantial returns—both monetary and in terms of human well-being—that successful prevention strategies can yield.
Novel and optimized mouse behavior enabled by fully autonomous HABITS: Home-cage Assisted Behavioral Innovation and Testing System
Authors: Yu Bowen , Li Penghai , Xu Haoze , Wang Yueming , Xu Kedi , Hao Yaoyao
Published: October 2024

Mice are among the most prevalent animal models used in neuroscience, benefiting from the extensive physiological, imaging and genetic tools available to study their brain. However, the development of novel and optimized behavioral paradigms for mice has been laborious and inconsistent, impeding the investigation of complex cognitions. Here, we present a home-cage assisted mouse behavioral innovation and testing system (HABITS), enabling free-moving mice to learn challenging cognitive behaviors in their home-cage without any human involvement. Supported by the general programming framework, we have not only replicated established paradigms in current neuroscience research but also developed novel paradigms previously unexplored in mice, resulting in more than 300 mice demonstrated in various cognition functions. Most significantly, HABITS incorporates a machine-teaching algorithm, which comprehensively optimized the presentation of stimuli and modalities for trials, leading to more efficient training and higher-quality behavioral outcomes. To our knowledge, this is the first instance where mouse behavior has been systematically optimized by an algorithmic approach. Altogether, our results open a new avenue for mouse behavioral innovation and optimization, which directly facilitates investigation of neural circuits for novel cognitions with mice.
A patient-centric knowledge graph approach to prioritize mutants for selective anti-cancer targeting
Authors: Gorostiola González Marina , IJzerman Adriaan P. , van Westen Gerard J.P.
Published: October 2024

Personalized oncology has revolutionized cancer treatment by targeting specific genetic aberrations in tumors. However, the identification of suitable targets for anti-cancer therapies remains a challenge. In this study, we introduce a knowledge graph approach to prioritize cancer mutations with clinical, functional, and structural significance as potential therapeutic targets. Focusing on the human kinome, we integrate protein-protein interaction and patient-centric mutation networks to construct a comprehensive network enriched with transcriptomic, structural, and drug response data, together covering five layers of information. Moreover, we make the constructed knowledge graph publicly available, along with a plethora of scripts to facilitate further annotation and expansion of the network. Interactive visualization resources are also provided, ensuring accessibility for researchers regardless of computational expertise and enabling detailed analysis by cancer type and individual layers of information. This comprehensive resource has the potential to identify relevant mutations for targeted therapeutic interventions, thereby advancing personalized oncology and improving patient outcomes.
Patterns of leaf, flower and fruit phenology and environmental relationships in a seasonal tropical forest in the Indian Eastern Himalaya
Authors: Datta Aparajita , Banerjee Soumya , Naniwadekar Rohit , Thapa Khem , Rathore Akanksha , Thapa Kumar , Brah Turuk , Nabum Tali , Shukla Ushma , Sidhu Swati , Borawake Noopur
Published: October 2024

Tree phenology plays an important role in determining the structure and function of tropical forest communities. However, there are few long-term studies on tree phenology from South Asia. We monitored 716 trees of 54 species monthly from 2011 to 2023 for leaf flush, flowering, and fruiting in Pakke Tiger Reserve, Arunachal Pradesh, India. We examined monthly patterns in the percentage of species and trees in leaf flush, flower and fruit and characterized phenological seasonality using circular statistics. Flowering periodicity was classified using Fourier analysis and we examined the relationships between phenological activity and temperature, rainfall, solar radiation and daylength using GAMLSS. Leaf flush and flowering were moderately seasonal, peaking in the warm dry season months of March to May. Fruiting patterns and their seasonality differed among dispersal modes. At the community level and for bird-dispersed species, fruiting was bimodal and relatively aseasonal, peaking in April and October. The highly seasonal fruiting of mammal-dispersed species peaked in October, while that of mechanically-dispersed species was bimodal and concentrated in the dry season months. The majority of species (78.13%) and trees (51.17%) flowered annually. Daylength, solar radiation and minimum temperature had significant nonlinear effects on phenology. This indicated the existence of narrow ranges of optimal climatic conditions for phenology, which could be affected by climate change. Our study emphasizes the need for long-term monitoring to rigorously quantify phenological patterns, particularly in the context of rapid global change.
Glycogen phosphorylase from the methanogenic archaeonMethanococcus maripaludis: Unique regulatory properties of a pyridoxal 5’-phosphate independent phosphorylase
Authors: González-Ordenes Felipe , Herrera-Soto Nicolas , Hernández-Cabello Leslie , Bustamante Catalina , Vallejos-Baccelliere Gabriel , Castro-Fernandez Victor , Guixé Victoria
Published: October 2024

Glycogen phosphorylase (GP) is a critical enzyme in glycogen metabolism. Even though methanogens from the archaeal ordersMethanosarcinalesandMethanococcalesare unable to grow on sugars, they store glycogen, which is metabolized through the glycogenolysis and glycolytic pathways when the carbon source for methanogenesis is depleted. Under these metabolic conditions, the activity of the GP enzyme is essential. To be active, all phosphorylases characterized to date require the cofactor pyridoxal 5’-phosphate (PLP). This cofactor is covalently bound via Schiff base to a strictly conserved lysine residue at the active site. Extensive GP sequence analysis of organisms from different domains of life shows strict conservation of active site residues despite significant differences in sequence length. Interestingly, in GP sequences of organisms from the orderMethanococcalesof archaea, a threonine residue replaces the conserved lysine involved in PLP binding. The purification and characterization of recombinant GP fromMethanococcus maripaludisshow that the enzyme exhibits glycogen phosphorylase activity and high specificity for glycogen as a substrate. Analysis of the PLP content performed by several methods, such as absorbance, fluorescence, cyanohydrin adduct formation, and mass spectrometry, confirmed the absence of PLP. The results demonstrate that an archaeal GP from the orderMethanococcalesperforms catalysis without the PLP cofactor, deviating from the well-established phosphorylase catalytic mechanism and revealing new scenarios for the glucosyltransferase reaction. Moreover, analysis of enzyme regulation shows that the activity is affected by various molecules, including nucleotides, intermediates of carbon metabolism, and phosphate species. Most of these molecules have not previously been identified as regulators of glycogen phosphorylases in prokaryotes. These results suggest that other GPs fromMethanococcalescan undergo complex regulation.
Investigation of the effect of physiological factors on resting-state and task-based functional connectivity
Authors: Askarinejad S. Emad , Poline Jean-Baptiste , Mitsis Georgios D.
Published: October 2024

Understanding the brain’s functional network through functional connectivity (FC) is crucial for gaining deeper insights into brain functional mechanism and identifying a potential biomarker for diagnosing neurological disorders. Despite the development of various FC measures, their reliability under different conditions remains under-explored. Moreover, physiological noise can obscure true neural activity, and accordingly, introduce errors into FC patterns. This issue necessitates further investigation. In this study, we evaluate and compare the performance of various methods using Local Field Potential and Blood-Oxygen-Level-Dependent signals across different conditions. We also examine the impact of physiological artifacts on BOLD-FC results. Our comprehensive assessment covers multiple modalities of brain signals, diverse task paradigms, and varying noise levels. Our findings reveal that while Granger Causality-based methods exhibit significant limitations, particularly with BOLD data, multivariate techniques (e.g. partial correlation) demonstrate greater robustness in distinguishing between different types of connections within the network. Notably, our results indicate that physiological artifacts substantially affect FC values, leading to erroneous connectivity estimates, especially with bivariate methods. This research offers a foundational analysis of the effects of physiological artifacts on FC results and provides valuable insights for future studies.
A Novel Engineered U7 Small Nuclear RNA Scaffold Greatly Increasesin vitroandin vivoADAR-Mediated Programmable RNA Base Editing
Authors: Byrne Susan M. , Burleigh Stephen M. , Fragoza Robert , Jiang Yue , Savva Yiannis , Pabon Ricky , Rainaldi Joseph , Portell Andrew , Mali Prashant , Briggs Adrian W.
Published: October 2024

Custom RNA base editing using the endogenous human Adenosine Deaminase Acting on RNA (ADAR) enzyme presents a promising approach for precision therapeutics, alleviating concerns of permanent DNA damage or immunogenicity from1foreign bacterial proteins such as CRISPR/Cas. ADAR can be directed to act on therapeutic RNA targets by antisense guide RNAs (gRNAs) that create a substrate for ADAR’s adenosine-to-inosine (effectively A-to-G) deamination activity. Delivery of gRNAs via a DNA expression construct provided by Adeno-Associated Virus (AAV) might allow life-long duration of the therapy. However, a major challenge for RNA editing using gene-encoded gRNAs and endogenous levels of ADAR is achieving sufficient gRNA activity inside cells, especially in therapeutic situations where AAV delivery may provide as low as one viral genome per cell. Here we show that embedding antisense gRNAs into a U7 small nuclear RNA (snRNA) framework and adding hnRNP A1 binding domains greatly increases the efficiency of custom RNA editing. This increased editing efficiency allows for detectable RNA editing from a single genomic insertion of gRNA construct per cell, which enabled a pooled library screen of 750+ gRNA variations to further improve the SmOPT U7 hairpin system. The screen revealed critical residues responsible for RNA editing and generated new SmOPT and U7 hairpin variants that further boosted RNA editing. The final design, combined with an improved synthetic U7 promoter, resulted in up to 76% targeted editing with a single integrated copy of construct per cell, representing a 10- to 100-fold increase over existing circular gRNA approaches. Using systemicin vivoAAV delivery, we achieved an unprecedented 75% RNA editing in the total brain of a mouse model of Hurler syndrome. Our novel SmOPT U7 system also improved published antisense oligos for DMD exon skipping, currently in clinical trials, by up to 25-fold in differentiated myoblasts, and therefore represents a universal scaffold for ADAR-based RNA editing as well as other antisense RNA therapies.
Characterization of newly isolated bacteriophages targeting carbapenem-resistantKlebsiella pneumoniae
Authors: Kim Bokyung , Kim Shukho , Choi Yoon-Jung , Shin Minsang , Kim Jungmin
Published: October 2024

Klebsiella pneumoniae, a Gram-negative opportunistic pathogen, is increasingly resistant to carbapenems in clinical settings. This growing problem necessitates the development of alternative antibiotics, with phage therapy being one promising option. In this study, we investigated novel phages targeting carbapenem-resistantKlebsiella pneumoniae(CRKP) and evaluated their lytic capacity against clinical isolates of CRKP. First, 23 CRKP clinical isolates were characterized using Multi-locus Sequence Typing (MLST), carbapenemase test, string test, and capsule typing. MLST classified the 23K. pneumoniaeisolates into 10 sequence types (STs), with the capsule types divided into nine known and one unknown type. From sewage samples collected from a tertiary hospital, 38 phages were isolated. Phenotypic and genotypic characterization of these phages was performed using Random Amplification of Polymorphic DNA-PCR (RAPD-PCR), transmission electron microscopy (TEM), and whole genome sequencing (WGS) analysis. Host spectrum analysis revealed that each phage selectively lysed strains sharing the same STs as their hosts, indicating ST-specific activity. These phages were subtyped based on their host spectrum and RAPD-PCR, identifying nine and five groups, respectively. Fourteen phages were selected for further analysis using TEM and WGS, revealing 13Myovirusesand onePodovirus. Genomic analysis grouped the phages into three clusters: one closely related toAlcyoneusvirus, one toAutographiviridae, and others toStraboviridae. Our results showed that the host spectrum ofK. pneumoniae-specific phages corresponds to the STs of the host strain. These 14 novel phages also hold promise as valuable resources for phage therapy against CRKP.
Acceptability and implementation considerations of the patient-collected rectal swab for sexually transmitted infections testing among men who have sex with men and transgender women in Kigali, Rwanda
Authors: Twahirwa Rwema Jean Olivier , Okonkwo Nneoma E. , Hamill Matthew M. , Lyons Carrie E. , Prata Menezes Neia , Makuza Jean Damascene , Nyombayire Julien , Rwibasira Gallican Nshogoza , Kagaba Aflodis , Sullivan Patrick , Allen Susan , Karita Etienne , Baral Stefan D.
Published: October 2024

Background

Rectal sexually transmitted infections (STI) are prevalent among men who have sex with men (MSM) and transgender women (TGW). Self-collection of rectal specimens is widely used globally, but limited data exist on its implementation in Africa. We report experiences of MSM/TGW self-collecting rectal STI specimens in Kigali.

Methods

From March to August 2018, 738 MSM/TGW were recruited in a cross-sectional study using respondent-driven sampling in Kigali. We tested forNeisseria gonorrheaandChlamydia trachomatisusing the Cepheid GeneXpert CT/NG platform on self-collected rectal swabs. Likert scales assessed self-collection difficulty and comfort. Ordered logistic regression analyses were performed to characterize factors associated with self-collection difficulty.

Results

Overall, 14%(106) identified as TGW. In total, 78%(577) found rectal swab self-collection easy/very easy, while 15%(108) found it difficult/very difficult. Most, 92%(679), were comfortable/very comfortable with the test, and 98%(730) said they would repeat the test in the future. In multivariable RDS-adjusted analyses, discomfort with the swab was positively associated with difficulty in self-collection (adjusted cumulative odds ratios ((aCOR): 7.9(95%CI: 4.9-12.8)) and having a prevalent rectal STI (aCOR: 4.19, 95%CI: 2.02-8.72) was significantly associated with difficulty.

Furthermore, 10%(75) of rectal swabs returned indeterminate results (65 invalid results and 10 errors).

Conclusion

Most MSM/TGW found self-collection of rectal swabs easy, comfortable, and collected valid samples. Self-collection of rectal swabs could be used alongside clinic- and community-based STI testing to improve diagnosis and treatment in Rwanda. However, measures to optimize sample collection and processing are needed to reduce the cost and clinical implications of indeterminate results
I answer to clinical scenarios as a real doctor because I “Think”: “ChatGPTo1” new reasoning ability
Authors: Mondillo Gianluca , Colosimo Simone , Perrotta Alessandra , Frattolillo Vittoria , Masino Mariapia , Marzuillo Pierluigi
Published: October 2024

The adoption of the ChatGPT o1 model represents a significant advancement in the management of clinical cases due to the introduction of a new structured reasoning capability, the “chain-of-thought reasoning” (CoT). In this study, 350 general medicine clinical cases were tested using ChatGPT o1 and ChatGPT o1 mini, and their performance was compared with ChatGPT 4o and ChatGPT 4o mini to evaluate diagnostic accuracy. The results showed that ChatGPT o1 achieved a correct answer rate of 93.4%, outperforming both ChatGPT 4o (82.2%) and the mini versions (ChatGPT o1 mini: 70.2% and ChatGPT 4o mini: 66.2%). The CoT technique enabled the model to provide more coherent and transparent responses, reducing the occurrence of so-called “hallucinations.” This study highlights how the ChatGPT o1 model can be a valuable tool in clinical practice, although its use requires supervision to ensure patient safety, especially in critical settings.
Identification of novel nutrient sensitive human yolk sac functions required for embryogenesis
Authors: White M , Arif-Pardy J , Bloise E , Connor KL
Published: October 2024

The human yolk sac (hYS) is essential for embryo nutrient biosynthesis/transport and development. However, there lacks a comprehensive study of hYS nutrient-gene interactions. Here we performed a secondary analysis of hYS transcript profiles (n=9 samples) to identify nutrient-sensitive hYS genes and regulatory networks, including those that associate with adverse perinatal phenotypes with embryonic origins. Overall, 14.8% highly expressed hYS genes are nutrient-sensitive; the most common nutrient cofactors for hYS genes are metals and B-vitamins. Functional analysis of highly expressed hYS genes reveals that nutrient-sensitive hYS genes are more likely to be involved in metabolic functions than hYS genes that are not nutrient-sensitive. Through nutrient-sensitive gene network analysis, we find that four nutrient-sensitive transcription regulators in the hYS (with zinc and/or magnesium cofactors) are predicted to collectively regulate 30.9% of highly expressed hYS genes. Lastly, we identify 117 nutrient-sensitive hYS genes that associate with an adverse perinatal outcome with embryonic origins. Among these, the greatest number of nutrient-sensitive hYS genes are linked to congenital heart defects (n=54 genes), followed by microcephaly (n=37). Collectively, our study characterises nutrient-sensitive hYS functions and improves understanding of the ways in which nutrient-gene interactions in the hYS may influence both typical and pathological development.
The Lifecycle of Electronic Health Record Data in HIV-Related Big Data Studies: A Qualitative Study of Instances of and Potential Opportunities to Minimize Bias
Authors: N'Diaye Arielle , Qiao Shan , Garrett Camryn M , Khushf George , Zhang Jiajia , Li Xiaoming , Olatosi Bankole
Published: October 2024

Background: Electronic health record (EHR) data are widely used in public health research, including HIV-related studies, but are limited by potential bias due to incomplete and inaccurate information, lack of generalizability, and lack of representativeness. This study explores how workflow processes within HIV clinics, among data scientists, and within state health departments may introduce and minimize bias within EHRs. Methods: Using a constructivist grounded theory approach, in-depth individual interviews were conducted with 16 participants purposively sampled in South Carolina from August 2023-April 2024. A focus group with 3 health department professionals with expertise in HIV disease surveillance was also conducted. Analysis was conducted as outlined by Charmaz (2006). Results: To reduce bias in EHR data, information entry forms should be designed to expansively include patient self-reported social determinants of health (SDOH) information. During data collection, healthcare providers should create a supportive healthcare environment, facilitate SDOH information disclosure, and accurately document patient information. Patients should have access to their EHRs to confirm that SDOH information are correctly recorded. During data curation, data scientists should inspect datasets for completeness, accuracy, and educate public health researchers on dataset limitations. During data management and utilization, health department professionals should crossmatch data across the state, customize data collection systems to reflect local needs, and provide community-based data education and stigma management. Conclusion: Study results suggest that future research is needed to understand how healthcare systems can be incentivized to create and implement EHR bias reduction strategies across all workflows and between stakeholders.
Feasibility of an App-Assisted and Home-Based Video Version of the Timed up and Go Test for Patients with Parkinson Disease: vTUG
Authors: Grobe-Einsler Marcus , Gerdes Anna , Feige Tim , Maas Vivian , Matthews Clare , García Alejandro Mendoza , Fages Laia Comas , Davies Elin Haf , Klockether Thomas , Falkenburger Björn H.
Published: October 2024

Background

Parkinson Disease (PD) is a progressive neurological disorder. Current therapeutic trials investigate treatments that can potentially modify the disease course. Testing their efficiency requires frequent and precise clinical outcome assessments (COA) of symptoms that remain problematic under symptomatic treatments, such as gait and balance. Home-based examinations may enhance patient compliance and, in addition, produce more reliable results by assessing patients more regularly in their familiar surroundings.

Objective

The objective of this study was to assess the feasibility of a digitized COA designed to video record the Timed up and Go (vTUG) test at home via a study-specific smartphone app for patients with PD.

Method

In this study, 28 patients were recruited and asked to perform at home each week a set of three consecutive vTUG tests over a period of 12 weeks using an app. The videos were subjected to a manual review to ascertain the durations of the individual vTUG phases, as well as to identify any errors or deviations in the setup that might have influenced the result. To evaluate the usability and user-friendliness of the vTUG and app, the System Usability Scale (SUS) and User Experience Questionnaire (UEQ) were administered to patients at the study end.

Results

Overall, 19 patients completed the 12-week study, 17 of which recorded 10 videos or more. A total of 706 vTUGs with complete timings were recorded. Random Forest Regression yielded “time to walk up” as the most important segment of the vTUG for predicting the total time. Variance of vTUG total time was significantly higher between weeks than it was between the three consecutive vTUGs at one time point [F(254,23) = 6.50, p < 0.001]. The correlation between vTUG total time and UPDRS III total score was weak (r = 0.24). Yet, correlation between vTUG and a derived gait subscore (UPDRS III items 9-13) was strong (r = .59). A linear mixed-effects model revealed a significant effect of patient-reported motion status on vTUG total time. Including additional variables such as UPDRS III gait subscore, different footwear, and chairs used, further improved the model fit.

Conclusion

Assessment of gait and balance by home-based vTUG is feasible. Factors influencing the read-out were identified and could be controlled for future use and longitudinal trials.
Measuring Multi-Joint Upper Limb Proprioceptive Position Sense in Children with Unilateral Spastic Cerebral Palsy using 3D Kinematics
Authors: Ratnadurai-Giridharan Shivakeshavan , Delfing Dalina , Robert Maxime T. , Kitago Tomoko , Gordon Andrew M. , Friel Kathleen M.
Published: October 2024

Background

Proprioceptive position sense (PPS), which provides the awareness of the positions of one’s limbs in space, is compromised in children with unilateral spastic cerebral palsy (USCP). Relationships between decreased PPS, skill acquisition, and performance are not well understood partly due to differences between measurement modalities of PPS. During assessments, individual joints are often constrained to a single plane of movement. We introduce ways to estimate PPS, simultaneously from multiple upper limb joints during unconstrained pose matching tasks, using 3D kinematics.

Methods

Nineteen children with USCP, 14 age-matched typically developing children (TDC) and, 16 typically developed adults (TDA) were recruited. Participants performed contralateral upper limb pose matching tasks while blindfolded. Using 3D kinematic data extracted by a VICON Nexus motion-capture system, three ways of measuring matching performance were calculated: joint angle symmetry, joint distance symmetry, and orientation symmetry. Mann-Whitney U tests were used to statistically compare scores between groups. Spearman’s rank correlation was used to investigate relationships between PPS symmetry measures and hand function in children with USCP.

Results

Children with USCP presented significantly lower angle, distance, and orientation symmetries compared to TDC. TDA scores were not statistically significantly different compared to TDC. In children with USCP, orientation symmetry measures strongly correlated with several clinical hand function scores such as the box and blocks test.

Conclusions

We introduced a new way to conveniently measure multi-joint PPS. Children with USCP presented lower PPS estimates compared to TDC. We also observed that orientation symmetry (limb co-ordination) strongly correlates with hand function.
Artificial Intelligence Applied to Electrocardiographic Images for Scalable Screening of Transthyretin Amyloid Cardiomyopathy
Authors: Sangha Veer , Oikonomou Evangelos K , Khera Rohan
Published: October 2024

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) remains largely under-recognized, under-diagnosed, and under-treated. We hypothesized that the myocardial remodeling of ATTR-CM may be detectable through artificial intelligence (AI) applied to 12-lead electrocardiographic (ECG) images.

Methods

Across 5 hospitals of a large U.S.-based hospital system, we identified patients with ATTR-CM, defined by the presence of a positive nuclear scan with an approved bone radiotracer or pharmacotherapy with an approved transthyretin stabilizer between 2015 and the first half of 2023. The development cohort consisted of 1,011 ECGs from 234 patients (age 79 [IQR:70-85] years, n=176 [17.4%] women), who were age- and sex-matched in a 10:1 ratio to 10,110 ECGs from 10,110 controls (age 79 [IQR:70-85] years, n=1,800 [17.7%] female). A convolutional neural network (CNN) pre-trained using a bio-contrastive pretext on ECGs before 2015 was fine-tuned for ATTR-CM using 5-fold cross-validation and subsequently tested in an independent set of cases (139 ECGs in 47 patients; age 80 [75-86] years, n=44 (31.7% women)) and matched controls (1390 ECGs and patients) from the second half of 2023.

Results

The AUROC (area under the receiver operating characteristic curve) of the AI-ECG model for discriminating ATTR-CM in the leave-out, temporally distinct dataset was 0.906 [95%CI: 0.89-0.94] (A), with a sensitivity of 0.85 [95%CI: 0.79-0.91] and specificity 0.80 [95%CI 0.78-0.82].

Conclusions

We demonstrate that AI applied directly to ECG images represents a promising and scalable approach for the screening of ATTR-CM.
MARLOWE: Taxonomic Characterization of Unknown Samples for Forensics UsingDe NovoPeptide Identification
Authors: Jenson Sarah C. , Chu Fanny , Barente Anthony S. , Crockett Dustin L. , Lamar Natalie C. , Merkley Eric D. , Jarman Kristin H.
Published: October 2024

We present a computational tool, MARLOWE, for source organism characterization of unknown, forensic biological samples. The intent of MARLOWE is to address a gap in applying proteomics data analysis to forensic applications. MARLOWE produces a list of potential source organisms given confident peptide tags derived fromde novopeptide sequencing and a statistical approach to assign peptides to organisms in a probabilistic manner, based on a broad sequence database. In this way, the algorithm assumes noa prioriknowledge of potential sources, and the probabilistic way peptides are taxonomically assigned and then scored enables results to be unbiased (within the constraints of the sequence database). In a proof-of-concept study, we examined MARLOWE’s performance on two datasets, the biodiversity dataset and theBacillus cereussuperspecies dataset. Not only did MARLOWE demonstrate successful characterization to true contributors in single source and binary mixtures in the biodiversity dataset, but also provided sufficient specificity to distinguish species within a bacterial superspecies group. These results suggest that MARLOWE is suitable for candidate- or lead-generation identification of single-organism and binary samples that can generate forensic leads and aid in selecting appropriate follow-on analyses in a forensic context.
Non-detection during excursions by citizen scientists modeled as a function of weather, season, list length, and individual preferences
Authors: Jacobusse Gert W. , Jongejans Eelke
Published: October 2024

INTRODUCTION

Citizen science is an increasingly valuable source of information about biodiversity. It is challenging to use this information for analysis of distribution and trends. The lack of a protocol leads to bias in observations and therefore data are not representative. The bias is a consequence of unequal detection probabilities, caused by different preferences and habits of citizen scientists.

METHODS

We propose to incorporate characteristics of these excursions in analyses of data collected by citizen scientists to improve estimates of the probability that a species is not detected and reported, even though it does occur. By limiting these models to areas that are known to be occupied, detection can be modeled separately without considering variation in occupancy. We apply this idea to 150 common species in the Southwest Delta of The Netherlands, and illustrate the data selection, the modeling process and the results using four species.

RESULTS

The strongest features to predict detection are the number of species during a visit (list length), earlier observations of the target species by the same observer, and the day of year. We compare three approaches to predict the total non-detection probability that takes all visits to an area into account. Predictions based on only the number of visits were outperformed by predictions that also take the list length into account. Our predictions based on all features combined consistently beat both other approaches, across all 10 species groups that were compared.

DISCUSSION

We thus show that explicitly modelling the characteristics of all visits to an occupied area results in estimation of non-detection probabilities, while providing insight into the causes of detection and reporting bias. Furthermore, predictions of our model provide a basis for quantifying the sampling effort in each area, which is a promising first step to correct bias in citizen science data when aiming to map a species’ distribution.
Neuronal activity regulating the dauer entry decision inCaenorhabditis elegans
Authors: Prakash Sharan J. , Seyedolmohadesin Maedeh , Zhang Mark G. , Cohen Sarah M. , Gharib Shahla , Venkatachalam Vivek , Sternberg Paul W.
Published: October 2024

The model nematodeCaenorhabditis eleganscan choose between two alternative developmental trajectories. Larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Previous studies showed that chemical signals from a secreted larval pheromone promote the dauer trajectory, and that their influence can be antagonised by increased availability of microbial food. The decision is known to be under neuronal control, involving both sensory and interneurons. To make an accurate decision, larvae must collect and compare complex patterns of environmental input over several hours of early larval development. The full composition of this circuit and the algorithm for decision-making are unknown. Here, we used cell-specific chemical silencing to systematically perturb several sensory and interneurons to further elucidate circuit composition. Our results suggest a role for gas-sensing neurons in regulating dauer entry. In addition, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA neurons. We found that calcium in ASI increases linearly in response to food, and similarly decreases in response to pheromone, revealing a cellular site of antagonism between these key chemical inputs. Notably, the ASI response persists well beyond removal of the food stimulus, thus encoding a memory of recent food exposure. In contrast, AIA reports instantaneous food availability, and is unaffected by pheromone. We discuss how these findings may inform our understanding of this long-term decision-making process.