bluuebunny/crossref_metadata_2025_split huggingface dataset:
Care seeking for diarrheal illness: a systematic review and meta-analysis
Authors: Wiens Kirsten E. , Miller Marissa H. , Costello Daniel J. , Solomon Ashlynn P. , Hilbert Skye M. , Shipper Andrea G. , Lee Elizabeth C. , Azman Andrew S. 
Published: December 2024

AbstractBackgroundMonitoring and treating diarrheal illness often rely on individuals seeking care at hospitals or clinics. Cases that seek care through pharmacies and community health workers (CHW) are frequently excluded from disease burden estimates, which are used to allocate mitigation resources. Studies on care seeking behavior can help identify these gaps but typically focus on children under five, even though diarrheal diseases like cholera and Enterotoxigenic E. coli affect all age groups. This study aimed to estimate the proportion of individuals seeking care for themselves or their children with diarrhea, considering different age groups, case definitions, and study settings.Methods and FindingsWe conducted a systematic review of population-based primary research studies published during 2000–2024 that examined care-seeking behavior for diarrhea. We included 166 studies from 62 countries. Hospitals and clinics were the most common source of care sought outside the home, with CHW and health posts rarely reported. Using a random-effects meta-analysis, we found substantial heterogeneity in care seeking between studies from low- and middle- income countries (I2= 99.3) and estimated that the proportion of diarrhea cases seeking care at a hospital or clinic was 32.8% on average (95% Confidence Interval (CI) 28.1% to 37.9%; prediction interval 3.3% to 87.5%). Although there were trends toward higher care-seeking for children compared to adults, substantial variation existed between studies, and the differences were not significant. We estimated that the adjusted odds of seeking care at a hospital or clinic were significantly higher for severe diarrhea and cholera compared to general diarrhea (Odds Ratio 3.43; 95% CI 1.71 to 6.88).ConclusionsOur findings confirm that passive surveillance through hospitals and clinics may substantially undercount the number of people with diarrhea, particularly those with milder symptoms, although this proportion varied widely. Additionally, our findings underscore the importance of including care seeking questions across all age groups in future studies, as we cannot assume lower care seeking for adults across all settings. Our study was limited by fewer data on care- seeking from health posts, traditional healers, and CHW compared to hospitals and clinics, highlighting a need for further research on these sources of care.
Association between epidural catheter tip malposition and anesthesiologists’ experience after graduation: a cross-sectional study using postoperative CT images
Authors: Matsuo Mitsuhiro , Sakamoto Natsumi , Takebe Mariko , Takazawa Tomonori 
Published: December 2024

AbstractObjectivesThis study aimed to examine the incidence of epidural catheter tip malposition using postoperative CT images, and investigated its relationship with anesthesiologist and patient characteristics.MethodsPatients who had undergone epidural anesthesia at our hospital during the previous 18 years, and who had a thorax and abdominal CT scan within 5 days after surgery were included. Malposition was defined if the tip of the catheter did not penetrate the ligamentum flavum in postoperative CT images.ResultsAmong 189 eligible patients (median age 71 years, range 15-89), 78 (41%) were female. The median number of years of postgraduate experience of the physicians inserting the epidural catheter was 5.7 years (range 2.0-35.4). All epidural catheters were inserted using the paramedian approach in the left lateral decubitus position. The puncture site was the middle (48%) or lower (49%) thoracic spine. Epidural catheter malposition was observed in 24 patients (12.7%, 95% confidence interval [CI] 8.3-18.3). Among these cases, catheter tips were located at the vertebrae (vertebral arches: 9, transverse processes: 2, spinous process: 1), in superficial soft tissue (erector spinae: 5, subcutaneous: 4), and in deep soft tissue (intervertebral foramina: 2, subpleural space: 1). Anesthesiologists in the malposition group had significantly more experience since graduation (median 10.1 years vs. 5.6 years, P=0.010). No other characteristics showed an association with catheter malposition.ConclusionsAnalysis of postoperative CT images revealed that the epidural catheter tip did not penetrate the ligamentum flavum in approximately 13% of cases. Our results suggest that even experienced anesthesiologists should be vigilant regarding proper catheter tip positioning.
Repeated net-tDCS of the hypothalamus appetite-control network reduces inhibitory control and sweet food intake in persons with overweight or obesity
Authors: Ester-Nacke Theresa , Veit Ralf , Thomanek Julia , Book Magdalena , Tamble Lukas , Beermann Marie , Löffler Dorina , Salvador Ricardo , Ruffini Giulio , Heni Martin , Birkenfeld Andreas L. , Plewnia Christian , Preissl Hubert , Kullmann Stephanie 
Published: December 2024

AbstractBackgroundReduced inhibitory control is associated with obesity and neuroimaging studies indicate that diminished prefrontal cortex activity influence eating behavior and metabolism. The hypothalamus regulates energy homeostasis and is functionally connected to cortical and subcortical regions especially the frontal areas.ObjectivesWe tested network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in appetite control.MethodsIn a randomized, double-blind parallel group design, 44 adults with overweight or obesity (BMI 30.6 kg/m2, 52.3 % female) received active (anodal or cathodal) or sham 12-channel net-tDCS on the hypothalamus appetite-control network for 25 minutes on three consecutive days while performing a Stop-Signal-Task to measure response inhibition. Before and after stimulation, state questionnaires assessed changes in desire to eat and food craving. Directly after stimulation, participants received a breakfast buffet to evaluatead-libitumfood intake. An oral glucose tolerance test was conducted at follow-up. Resting-state functional MRI was obtained at baseline and follow-up.ResultsThe Stop-Signal Reaction Time (SSRT) was shorter in both active groups versus sham, indicating improved response inhibition. Additionally, a stronger increase in hypothalamic functional connectivity was associated with shorter SSRT. Caloric intake of sweet food was lower in the anodal group versus sham, but no main effects between groups were observed on total and macronutrient intake, food craving ratings and desire to eat. At follow-up, no differences were observed between groups on peripheral metabolism.ConclusionOur study suggests that modulating hypothalamic functional network connectivity patterns via net-tDCS may improve food choice and inhibitory control.Graphical AbstractHighlightsActive net-tDCS groups showed better inhibitory control compared to the sham group.Stronger increase in hypothalamic functional connectivity associated with better inhibitory control after active net-tDCS.No differences were found between the active net-tDCS and sham groups for total kilocaloric intake.Anodal net-tDCS showed lower sweet food intake compared to the sham group.
Programming the elongation of mammalian cell aggregates with synthetic gene circuits
Authors: Courte Josquin , Chung Christian , Jain Naisargee , Salazar Catcher , Phuchane Neo , Grosser Steffen , Lam Calvin , Morsut Leonardo 
Published: December 2024

AbstractA key goal of synthetic morphogenesis is the identification and implementation of methods to control morphogenesis. One line of research is the use of synthetic genetic circuits guiding the self-organization of cell ensembles. This approach has led to several recent successes, including control of cellular rearrangements in 3D via control of cell-cell adhesion by user-designed artificial genetic circuits. However, the methods employed to reach such achievements can still be optimized along three lines: identification of circuits happens by hand, 3D structures are spherical, and effectors are limited to cell-cell adhesion. Here we show the identification, in a computational framework, of genetic circuits for volumetric axial elongation via control of proliferation, tissue fluidity, and cell-cell signaling. We then seek to implement this design in mammalian cell aggregatesin vitro.We start by identifying effectors to control tissue growth and fluidityin vitro. We then combine these new modules to construct complete circuits that control cell behaviors of interest in space and time, resulting in measurable tissue deformation along an axis that depends on the engineered signaling modules. Finally, we contextualizein vitroandin silicoimplementations within a unified morphospace to suggest further elaboration of this initial family of circuits towards more robust programmed axial elongation. These results and integratedin vitro/in silicopipeline demonstrate a promising method for designing, screening, and implementing synthetic genetic circuits of morphogenesis, opening the way to the programming of various user-defined tissue shapes.
Self-organizing human heart assembloids with autologous and developmentally relevant cardiac neural crest-derived tissues
Authors: Kostina Aleksandra , Kiselev Artem , Huang Amanda , Lankerd Haley , Caywood Sammantha , Jurado-Fernandez Ariadna , Volmert Brett , O’Hern Colin , Juhong Aniwat , Liu Yifan , Qiu Zhen , Park Sangbum , Aguirre Aitor 
Published: December 2024

ABSTRACTNeural crest cells (NCCs) are a multipotent embryonic cell population of ectodermal origin that extensively migrate during early development and contribute to the formation of multiple tissues. Cardiac NCCs play a critical role in heart development by orchestrating outflow tract septation, valve formation, aortic arch artery patterning, parasympathetic innervation, and maturation of the cardiac conduction system. Abnormal migration, proliferation, or differentiation of cardiac NCCs can lead to severe congenital cardiovascular malformations. However, the complexity and timing of early embryonic heart development pose significant challenges to studying the molecular mechanisms underlying NCC-related cardiac pathologies. Here, we present a sophisticated functional model of human heart assembloids derived from induced pluripotent stem cells, which, for the first time, recapitulates cardiac NCC integration into the human embryonic heartin vitro. NCCs successfully integrated at developmentally relevant stages into heart organoids, and followed developmental trajectories known to occur in the human heart. They demonstrated extensive migration, differentiated into cholinergic neurons capable of generating nerve impulses, and formed mature glial cells. Additionally, they contributed to the mesenchymal populations of the developing outflow tract. Through transcriptomic analysis, we revealed that NCCs acquire molecular features of their cardiac derivatives as heart assembloids develop. NCC-derived parasympathetic neurons formed functional connections with cardiomyocytes, promoting the maturation of the cardiac conduction system. Leveraging this model’s cellular complexity and functional maturity, we uncovered that early exposure of NCCs to antidepressants harms the development of NCC derivatives in the context of the developing heart. The commonly prescribed antidepressant Paroxetine disrupted the expression of a critical early neuronal transcription factor, resulting in impaired parasympathetic innervation and functional deficits in cardiac tissue. This advanced heart assembloid model holds great promise for high-throughput drug screening and unraveling the molecular mechanisms underlying NCC-related cardiac formation and congenital heart defects.IN BRIEFHuman neural crest heart assembloids resembling the major directions of neural crest differentiation in the human embryonic heart, including parasympathetic innervation and the mesenchymal component of the outflow tract, provide a human-relevant embryonic platform for studying congenital heart defects and drug safety.
spotPCR: A Rapid and Efficient Approach for Indexing Individual Template Molecules using Unique Molecular Identifiers
Authors: Limberis Jason D , Nagel Roland J , Chakravorty Soumitesh , Block Dena , Dewell Scot , Nalyvayko Alina , Metcalfe John Z 
Published: December 2024

AbstractLow-frequency mutations provide valuable insights in various fields, including drug resistance identification, cancer and infectious disease research. One promising strategy to enhance the sensitivity and specificity of mutation detection is the incorporation of unique molecular identifiers (UMIs) during polymerase chain reaction (PCR) amplification and before deep sequencing. However, conventional methods for UMI incorporation oRen necessitate multiple labor-intensive steps. spotPCR (Specific Primer Limited Unique Molecular Identifier Tagging PCR) overcomes these challenges, streamlining the UMI tagging process.
STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis
Authors: Olatoke Tasnim , Zhang Erik Y. , Wagner Andrew , He Quan , Li Siru , Astreinidis Aristotelis , McCormack Francis X. , Xu Yan , Yu Jane J. 
Published: December 2024

ABSTRACTLymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex. Although it is known that hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to TSC2 gene mutations contributes to aberrant cell growth in LAM lung, tumor origin and invasive mechanism remain unclear. To determine molecular drivers responsible for aberrant LAM cell growth, we performed integrative single-cell transcriptomic analysis and predicted that STAT1 interacts with Pre-B cell leukemia transcription factor (PBX1) to regulate LAM cell survival. Here, we show activation of STAT1 and STAT3 proteins in TSC2- deficient LAM models. Fludarabine, a potent STAT1 inhibitor, induced the death of TSC2- deficient cells, increased caspase-3 cleavage, and phosphorylation of necroptosis marker RIP1. Fludarabine treatment impeded lung colonization of TSC2-deficient cells and uterine tumor progression, associated with reduced percentage of PCNA-positive cells in vivo. Interestingly, IFN-γ treatment increased STAT1 phosphorylation and PD-L1 expression, indicating that STAT1 aids TSC2-deficient tumor cells in evading immune surveillance in LAM. Our findings indicate that STAT1 signaling is critical for LAM cell survival and could be targeted to treat LAM and other mTORC1 hyperactive tumors.
Sneezing in response to bright light exposure: A case study in a photic sneezer
Authors: Bickerstaff Lucien , Trinkl Josef , Munkwitz Stephan , Spitschan Manuel 
Published: December 2024

AbstractBackgroundThe photic sneeze reflex (PSR) is a widespread, yet understudied phenomenon characterised by sneezing in response to bright-light exposure, reportedly affecting around 30% of the general population. Our goals were to collect real-world data to characterise PSR-inducing naturalistic light conditions, and to develop an indoor protocol to reliably induce the PSR in affected individuals using parametric stimuli.MethodsThis study was carried out on one male adult affected by photic sneezing (n=1). To characterise naturalistic light conditions eliciting photic sneezing, real-world light exposure was measured over a 30-day period, while logging PSR events. To study photic sneezing in response to artificial stimuli, a setup including a multi-primary LED source and an integrating sphere was used to present 30-second light stimuli to the participant while collecting pupillometric data with an eye-tracker.Results82 photic sneeze events were recorded, with an average of 2.73 sneezes per day and a range of 1 to 6 sneezes per event. At a sneeze event, illuminance is on average ten times bigger than five minutes before the sneeze event. A significant increase in illuminance is observed around 2 minutes before the sneeze event. Light levels go back down to pre-sneeze levels within 10 minutes after sneezing. Despite exposure to more than 150 stimuli, no sneeze could be artificially induced in the participant. However, a strong tickling sensation was consistently reported, especially for high illuminance settings.ConclusionsReal-world light data confirmed that a sudden increase in environmental lighting conditions can induce photic sneezing. Further analysis could be relevant on instances of illuminance increments not eliciting a photic sneeze. The experimental setup only elicited tickling sensations, but with further testing and optimisation, it is reasonable to assume that it would reliably induce photic sneezes, thereby opening further mechanistic study of this intriguing phenomenon.
Exclusive cataloging of near-complete genomes unveils novel functional insights into the human gut microbiome
Authors: Ma Junyeong , Kim Nayeon , Cha Jun Hyung , Kim Wonjong , Kim Chan Yeong , Yang Sunmo , Beck Samuel , Lee Insuk 
Published: December 2024

AbstractUnderstanding the human gut microbiome requires comprehensive genomic catalogs, yet many existing ones lack geographic diversity and include numerous medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of genomic regions, potentially leading to inaccurate functional insights into the microbiome. To address these limitations, we developed an enhanced Human Reference Gut Microbiome (HRGM2), a catalog of near-complete (NC) MAGs (completeness ≥90% and contamination ≤5%) and isolate genomes (collectively ‘NC genomes’) with extensive geographic sampling. HRGM2 comprises 155,211 non-redundant NC genomes from 4,824 prokaryotic species across 41 countries, representing a 66% increase in genome count and a 50% boost in species diversity over the NC genome-based Unified Human Gastrointestinal Genome catalog. Extensive sampling from Africa revealed previously undetectable Africa-associated phyla, highlighting microbial links between humans and the environment. Given the high species complexity of the human gut microbiota, DNA-based species profiling using HRGM2 outperforms marker-based profiling in accuracy. Profiling genomes with enhanced protein functional annotations provides reliable insights into the microbiome. Notably, with exclusive use of NC genomes, HRGM2 enhances assessments of microbiota metabolic capacities and supports genome-scale metabolic models (GEMs) of entire gut microbiota. These findings offer novel functional perspectives on the human gut microbiome, achievable only through high-quality genome cataloging.
Calibration-free estimation of field dependent aberrations for single molecule localization microscopy across large fields of view
Authors: Droste Isabel , Schuitema Erik , Khan Sajjad , Heldens Stijn , van Werkhoven Ben , Lidke Keith A. , Stallinga Sjoerd , Rieger Bernd 
Published: December 2024

AbstractImage quality in single molecule localization microscopy (SMLM) depends largely on the accuracy and precision of the localizations. While under ideal imaging conditions the theoretically obtainable precision and accuracy are achieved, in practice this changes if (field dependent) aberrations are present. Currently there is no simple way to measure and incorporate these aberrations into the Point Spread Function (PSF) fitting, therefore the aberrations are often taken constant or neglected all together. Here we introduce a model-based approach to estimate the field-dependent aberration directly from single molecule data without a calibration step. This is made possible by using nodal aberration theory to incorporate the field-dependency of aberrations into our fully vectorial PSF model. This results in a limited set of aberration fit parameters that can be extracted from the raw frames without a bead calibration measurement, also in retrospect. The software implementation is computationally efficient, enabling fitting of a full 2D or 3D dataset within a few minutes. We demonstrate our method on 2D and 3D localization data of microtubuli and nuclear pore complexes over fields of view (FOV) of up to 180 μm and compare it with spline-based fitting and a deep learning based approach.
Gene flow can reveal ghost lineages
Authors: Tricou Théo , Marsot Enzo , Boussau Bastien , Tannier Éric , de Vienne Damien M. 
Published: December 2024

AbstractGhost species, encompassing extinct, unknown, and unsampled taxa, vastly outnumber those typically included in phylogenetic analyses. This hidden diversity has been shown to influence the study of horizontal gene flow (e.g., introgression and horizontal gene transfer) by complicating the phylogenetic signals commonly used for their detection.In this work, we explore the potential of horizontal gene transfer (HGT) detection methods based on phylogenies (i.e., reconciliation methods) to reveal and quantify ghost diversity along the branches of a species phylogeny. We succinctly present the theoretical framework for this approach, and we demonstrate, using simple simulations, that HGT signals, as interpreted by a reconciliation method, can reveal the presence and phylogenetic position of ghost clades, despite the absence of genomic data for these taxa. We anticipate possible limitations and difficulties in using HGT detection to explore ghost diversity and suggest promising approaches to address or circumvent them. Altogether, this proof of concept opens new lines of research for the future: a scarce fossil record and a large proportion of unknown lineages, especially in Archaea and Bacteria, does not equate to an absence of information for evolutionary studies.