bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeatability of Pulse Oximetry Measurements in Children During Triage in Two Ugandan Hospitals
Authors: Asdo Ahmad , Mawji Alishah , Agaba Collins , Komugisha Clare , Novakowski Stefanie K , Pillay Yashodani , Kaumu Stephen , Wiens Matthew O , Akech Samuel , Tagoola Abner , Kissoon Niranjan , Ansermino J Mark , Dunsmuir Dustin 
Published: December 2022

ABSTRACTBackgroundIn low- and middle-income countries, health workers use pulse oximeters for intermittent spot measurements of SpO2. However, the accuracy and reliability when used for spot measurements has not been determined. We evaluated the repeatability of spot measurements, and the ideal observation time of measurement to guide recommendations during spot check measurements.MethodsTwo one-minute measurements were done for the 3,903 subjects enrolled in the study, collecting 1Hz SpO2and signal quality index (SQI) data. The repeatability between the two measurements was assessed using an intraclass correlation coefficient (ICC), calculated using a median of all seconds of non-zero SpO2values for each recording (any quality, Q1), and again with a quality filter only using seconds with SQI ≥ 90% (good quality, Q2). The ICC was also calculated for both these conditions using subsets of the minute, in increasing increments of 5 seconds, up to the whole minute. Lastly, the whole minute ICC was calculated with good quality (Q2), including only records where both measurements had a mean SQI > 70% (Q3).FindingsThe repeatability ICC with condition Q1 was 0.591 (95% confidence interval (CI) = 0.570, 0.611). Using only the first 5 seconds of each measurement reduced the repeatability to 0.200 (95% CI = 0.169, 0.230). Filtering with Q2, the whole minute ICC was 0.855 (95% CI = 0.847, 0.864). The ICC did not improve beyond the first 35 seconds. For Q3, the repeatability rose to 0.908 (95% CI = 0.901, 0.914).ConclusionsTraining guidelines must emphasize the importance of signal quality and duration of measurement, targeting a minimum of 35 seconds of adequate-quality, stable data. In addition, the design of new devices should incorporate user prompts and force quality checks to encourage more accurate pulse oximetry measurement.Trial RegistrationClinical Trials.govIdentifier:NCT04304235, Registered 11 March 2020.
The Gender Gap in Leading Medical Journals - a Computational Audit
Authors: Brück Oscar 
Published: December 2022

ABSTRACTBackgroundPublication track record can impact careers of researchers. Therefore, monitoring gender representation in medical research is required to achieve equity in academia.MethodsWe gathered bibliometric data on original research articles published between 2010 and 2019 inThe New England Journal of Medicine, Nature Medicine, Journal of the American Medical Association, The BMJ, andThe Lancetusing the Web of Science indexing database. We associated publication and citation frequency with author gender, count, and institute affiliation, and research keywords.FindingsWe analyzed 10,558 articles and found that women published and were cited less than men. There were fewer women as senior (24.8%) than leading authors (34.5%, p<0.001). The proportion of female authors varied by country with 9.1% last authors from Austria, 0.9% from Japan, and 0.0% from South Korea. The gender gap decreased longitudinally and faster for last (−24.0 articles/year, p<0.001) than first authors (−14.5 articles/year, p=0.024). The trend varied by country and even increased in China and Israel. Author count was associated with higher citation count (R0.46, p<0.001) as well as with male first (n=11 vs. n=10, p<0.001) and last authors (n=11 vs. n=10, p<0.001). We also discovered that usage of research keywords varied by gender, and it partly accounted for the difference in citation counts by gender.InterpretationGender representation has increased both at the leading and senior author levels although with country-specific variability. The study frame can be easily applied to any journal and time period to monitor changes in gender representation in science.
Investigating the association between fasting insulin, erythrocytosis and HbA1c through Mendelian randomization and observational analyses
Authors: Nguyen Anthony , Khafagy Rana , Hashemy Habiba , Kuo Kevin H.M. , Roshandel Delnaz , Paterson Andrew D. , Dash Satya 
Published: December 2022

AbstractBackgroundInsulin resistance (IR)/hyperinsulinemia (HI), are early abnormalities in the etiology of prediabetes (preT2D) and type 2 diabetes (T2D). IR/HI also associate with increased erythrocytosis. Hemoglobin A1c (HbA1c) is commonly used to diagnose and monitor preT2D/T2D, but can be influenced by erythrocytosis independent of glycemi.MethodsWe undertook bidirectional Mendelian randomization (MR), in individuals of European ancestry, to investigate potential causal associations between increased fasting insulin adjusted for BMI (FI), erythrocytosis and its non-glycemic impact on HbA1c. We investigated the association between Triglyceride-glucose index (TGI), a surrogate measure of IR/HI, and glycation gap (difference between measured HbA1c and predicted HbA1c derived from linear regression of fasting glucose) in people with normoglycemia and preT2D.ResultsInverse variance weighted MR (IVWMR) suggests increased FI increases haemoglobin (b=0.54+/-0.09, p=2.7 × 10-10), red cell count (RCC, b=0.54+/-0.12, p=5.38×10-6) and reticulocyte (RETIC, b=0.70+/-0.15, p=2.18×10-6). Multivariable MR indicates increased FI does not impact HbA1c (b=0.23+/-0.16, p=0.162) but reduces HbA1c after adjustment for T2D (b=0.31+/-0.13, p=0.016). Increased haemoglobin (b=0.03+/-0.01, p=0.02), RCC (b=0.02+/-0.01, p=0.04) and RETIC (b=0.03+/-0.01, p=0.002) might modestly increase FI. Increased TGI associates with decreased glycation gap, i.e. measured HbA1c was lower than expected based on fasting glucose, (b=-0.09±0.009, p<0.0001) in people with preT2D but not in normoglycemia (b=0.02±0.007, p<0.0001).ConclusionsMR suggests increased FI increases erythrocytosis and might potentially decrease HbA1c by non-glycemic effects. Increased TGI, a surrogate measure of increased FI, associates with lower-than-expected HbA1 in people with preT2D. These findings merit confirmatory studies to evaluate its clinical significance.
MetaPathPredict: A machine learning-based tool for predicting metabolic modules in incomplete bacterial genomes
Authors: Geller-McGrath D. , Konwar Kishori M. , Edgcomb V.P. , Pachiadaki M. , Roddy J. W. , Wheeler T. J. , McDermott J. E. 
Published: December 2022

AbstractThe reconstruction of complete microbial metabolic pathways using ‘omics data from environmental samples remains challenging. Computational pipelines for pathway reconstruction that utilize machine learning methods to predict the presence or absence of KEGG modules in incomplete genomes are lacking. Here, we present MetaPathPredict, a software tool that incorporates machine learning models to predict the presence of complete KEGG modules within bacterial genomic datasets. Using gene annotation data and information from KEGG module databases, MetaPathPredict employs neural network and XGBoost stacked ensemble models to reconstruct and predict the presence of KEGG modules in a genome. MetaPathPredict can be used as a command line tool or as an R package, and both options are designed to be run locally or on a compute cluster. In our benchmarks, MetaPathPredict makes robust predictions of KEGG module presence within highly incomplete genomes.
A Synaptic Corollary Discharge Signal Suppresses Midbrain Visual Processing During Saccade-Like Locomotion
Authors: Ali Mir Ahsan , Lischka Katharina , Preuss Stephanie J. , Trivedi Chintan A. , Bollmann Johann H. 
Published: December 2022

ABSTRACTIn motor control, the brain not only sends motor commands to the periphery, but it also generates concurrent internal signals known as corollary discharge that influence the processing of sensory information around the time of movement. Corollary discharge signals are important for the brain to identify sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from single neurons in the optic tectum of zebrafish, we discovered an inhibitory synaptic signal which was temporally locked to spontaneous and visually driven swim patterns. This motor-related synaptic signal transiently suppressed tectal output and was appropriately timed to counteract visually driven excitatory input arising from the fish’s own motion. High-resolution calcium imaging revealed brief, highly localized post-swim signals in the tectal neuropil, suggesting that corollary discharge enters the tectum in its most superficial layer. Our results demonstrate how spurious visual input is suppressed during self-motion by motor-related phasic inhibition in the tectum. This may help explain perceptual saccadic suppression observed in many species.
CherryML: Scalable Maximum Likelihood Estimation of Phylogenetic Models
Authors: Prillo Sebastian , Deng Yun , Boyeau Pierre , Li Xingyu , Chen Po-Yen , Song Yun S. 
Published: December 2022

AbstractPhylogenetic models of molecular evolution are central to diverse problems in biology, but maximum likelihood estimation of model parameters is a computationally expensive task, in some cases prohibitively so. To address this challenge, we here introduce CherryML, a broadly applicable method that achieves several orders of magnitude speedup. We demonstrate its utility by applying it to estimate a general 400 × 400 rate matrix for amino acid co-evolution at protein contact sites.
High-resolution glucose tracing and in situ imaging reveals regulated lactate production in human pancreatic β cells
Authors: Cuozzo Federica , Viloria Katrina , Shilleh Ali H. , Nasteska Daniela , Frazer-Morris Charlotte , Jiao Zicong , Boufersaoui Adam , Marzullo Bryan , Smith Hannah R. , Bonner Caroline , Kerr-Conte Julie , Pattou Francois , Nano Rita , Piemonti Lorenzo , Johnson Paul R.V. , Spiers Rebecca , Roberts Jennie , Lavery Gareth G. , Clark Anne , Ceresa Carlo D.L. , Hodson Leanne , Davies Amy P. , Rutter Guy. A. , Oshima Masaya , Scharfmann Raphaël , Merrins Matthew J. , Akerman Ildem , Tennant Daniel A. , Ludwig Christian , Hodson David J. 
Published: December 2022

ABSTRACTUsing13C6glucose labeling coupled to GC-MS and 2D1H-13C HSQC NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning β cell function. In both mouse and human islets, the contribution of glucose to the TCA cycle is similar. Pyruvate-fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is six-fold higher in human islets. Human islets express LDH, with low-moderateLDHAexpression and β cell-specific LDHB expression. LDHB inhibition increases glucose-dependent lactate generation in mouse and human β cells, and decreases Ca2+-spiking frequency without affecting ATP/ADP levels. Thus, we show that LDHB limits glucose-stimulated lactate generation in β cells. Further studies are warranted to understand how lactate impacts β cell metabolism and/or function.HIGHLIGHTSHuman and rodent islets generate lactate following glucose stimulation.β cells specifically express LDHB, which acts to limit lactate generation.LDHB inhibition influences Ca2+spiking frequency without affecting ATP/ADP ratio.eTOCCuozzo et al show that glucose-stimulated rodent and human islets generate lactate. Transcriptomic and imaging analyses reveal that LDHB is specifically expressed in β cells and unexpectedly restrains lactate production. LDHB expression and thus regulated lactate generation might reflect a key mechanism underlying β cell metabolism, function and survival.
The vacuolar sugar transporterEarly Response to Dehydration 6-Like4regulates fructose signaling and plant growth
Authors: Khan Azkia , Cheng Jintao , Kitashova Anastasia , Fürtauer Lisa , Nägele Thomas , Picco Cristiana , Scholz-Starke Joachim , Keller Isabel , Neuhaus H. Ekkehard , Pommerrenig Benjamin 
Published: December 2022

AbstractRegulation of intracellular sugar homeostasis is maintained by regulation of activities of sugar import and export proteins residing at the tonoplast. We show here that the EARLY RESPONSE TO DEHYDRATION6-LIKE4 protein, being the closest homolog to the proton/glucose symporter ERDL6, resides in the vacuolar membrane. Gene expression and subcellular fractionation studies indicated that ERDL4 was involved in fructose allocation across the tonoplast. Overexpression ofERDL4increased total sugar levels in leaves, due to a concomitantly induced stimulation ofTST2expression, coding for the major vacuolar sugar loader. This conclusion is supported by the finding thattst1-2knockout lines overexpressingERDL4lack increased cellular sugar levels. ERDL4 activity contributing to the coordination of cellular sugar homeostasis is also indicated by two further observations. Firstly,ERDL4andTSTgenes exhibit an opposite regulation during a diurnal rhythm, and secondly, theERDL4gene is markedly expressed during cold acclimation representing a situation in which TST activity needs to be upregulated. Moreover,ERDL4-overexpressing plants show larger size of rosettes and roots, a delayed flowering time and increased total seed yield. Consistently,erdl4knock-out plants show impaired cold acclimation and freezing tolerance along with reduced plant biomass. In summary, we show that modification of cytosolic fructose levels influences plant organ development and stress tolerance.One sentence summaryThe activity of the vacuolar sugar porter ERDL4 is important for balanced cytosolic monosaccharide homeostasis and influences plant growth and cold response in ArabidopsisThe author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors is: Benjamin Pommerrenig (pommerre@bio.uni-kl.de).
Liam tackles complex multimodal single-cell data integration challenges
Authors: Rautenstrauch Pia , Ohler Uwe 
Published: December 2022

AbstractMulti-omics characterization of single cells holds outstanding potential for profiling gene regulatory states of thousands of cells and their dynamics and relations. How to integrate multimodal data is an open problem, especially when aiming to combine data from multiple sources or conditions containing biological and technical variation. We introduce liam, a flexible model for the simultaneous horizontal and vertical integration of paired single-cell multimodal data. Liam learns a joint low-dimensional representation of two concurrently measured modalities, which proves beneficial when the information content or quality of the modalities differ. Its integration accounts for complex batch effects using a tuneable combination of conditional and adversarial training and can be optimized using replicate information while retaining selected biological variation. We demonstrate liam’s superior performance on multiple multimodal data sets, including Multiome and CITE-seq data. Detailed benchmarking experiments illustrate the complexities and challenges remaining for integration and the meaningful assessment of its success.
Mitochondrial folate metabolism inhibition drives differentiation through mTORC1 mediated purine sensing
Authors: Zarou Martha M. , Rattigan Kevin M. , Sarnello Daniele , Dawson Amy , Ianniciello Angela , Dunn Karen , Copland Mhairi , Sumpton David , Vazquez Alexei , Helgason G. Vignir 
Published: December 2022

AbstractSupporting cell proliferation through nucleotide biosynthesis is an essential requirement for cancer cells. Hence, inhibition of folate-mediated one carbon (1C) metabolism, which is required for nucleotide synthesis, has been successfully exploited in anti-cancer therapy. Here, we reveal that mitochondrial folate metabolism is upregulated in patient-derived leukaemic stem cells (LSCs). We demonstrate that inhibition of mitochondrial 1C metabolism through impairment ofde novopurine synthesis has a cytostatic effect on chronic myeloid leukaemia (CML) cells. Consequently, changes in purine nucleotide levels lead to activation of AMPK signalling and suppression of mTORC1 activity. Notably, suppression of mitochondrial 1C metabolism increases expression of erythroid differentiation markers. Moreover, we find that increased differentiation occurs independently of AMPK signalling and can be reversed through reconstitution of purine levels and reactivation of mTORC1. Of clinical relevance, we identify that combination of 1C metabolism inhibition with imatinib, a frontline treatment for CML patients, decreases the number of therapy-resistant CML LSCs in a patient-derived xenograft model. Our results highlight a novel role for folate metabolism and purine sensing in stem cell fate decisions and leukaemogenesis.
Sex-biasedYap1oncogene function
Authors: Abdelfattah Nourhan , Natarajan Sivaraman , Maldonado Jose , Tran Han Nhat , McMinimy Rachael , Borland Hannah , Chen Shu-hsia , Camargo Fernando , Olson James , George Joshy , Yun Kyuson 
Published: December 2022

ABSTRACTThe incidence of many human cancers differs according to sex, but little is known about the interplay between oncogenic events and sex as a variable in tumorigenesis. Here we report that the oncogeneYap1is sexually dimorphic in medulloblastoma progression and immune suppression. We show thatYap1promotes stemness and blocks differentiation in sonic hedgehog (SHH)-subtype medulloblastoma by at least two distinct but complementary molecular mechanisms to regulate the RNA expression and protein functions ofSox2, Atoh1, NeuroD1, and Zic1/2. Yap1also promotes an immune suppressive tumor microenvironment by directly regulatingCsf1, Igf1,andIgfbp3transcription and modulating IL6-JAK-STAT3, TNFR1, TGF-β, and CCL5 immune pathways. Notably,Yap1function is more critical in males and this is evolutionarily conserved: genes downstream of YAP1 identified in mouse models stratify male but not female medulloblastoma patient survival. In summary, we demonstrate a sex-based function for an oncogene, underscoring the critical need to incorporate sex as a variable in cancer mechanism and clinical response studies, particularly those involving YAP1.
TManual: Assistant for manually measuring length development in structures built by animals
Authors: Mizumoto Nobuaki 
Published: December 2022

AbstractStructures built by animals are extended phenotypes, and animal behavior can be better understood by recording the temporal development of structure construction. For most subterranean and wood-boring animals, these structures consist of gallery systems, such as burrows made by mice, tunnel foraging by termites, and nest excavation in ants. Measurement of the length development of such structures is often performed manually. However, it is time-consuming and cognitively costly to track length development in nested branching structures, hindering the quantitative determination of temporal development.Here, I introduce TManual, which aids the manual measurement of structure length development using a number of images. TManual provides a user interface to draw gallery structures and take over all other processes handling input datasets (e.g., zero-adjustment, scaling the units, measuring the length, assigning gallery identities, and extracting network structures). Thus, users can focus on the measuring process without interruptions.As examples, I provide the results of the analysis of a dataset of tunnel construction by three termite species after successfully processing 1,125 images in ∼3 h. The output datasets clearly visualized the interspecific variation in tunneling speed and branching structures. Furthermore, I applied TManual to a complex gallery system by another termite species and extracted network structures.Measuring the lengths of objects from images is an essential task in biological observation. TManual helps users handle many images in a realistic time scale, enabling a comparative analysis across a wide array of species. TManual does not require programming skills and outputs a tidy data frame in CSV format. Therefore, it is suitable for any user who wants to perform image analysis for length measurements.
Cdkn2aregulates beige fat maintenance through BECN1-mediated autophagy
Authors: Wu Ruifan , Park Jooman , Qian Yanyu , Shi Zuoxiao , Hu Ruoci , Yuan Yexian , Xiong Shaolei , Wang Zilai , Yan Gege , Ong Sang-Ging , Song Qing , Song Zhenyuan , Mohamed Abeer , Xu Pingwen , He Congcong , Arpke Robert W. , Kyba Michael , Shu Gang , Jiang Qingyan , Jiang Yuwei 
Published: December 2022

SUMMARYA potential therapeutic target to curb the obesity and diabetes epidemic is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role ofCdkn2aas a molecular pedal for the beige-to-white transition. Beige adipocytes lackingCdkn2aexhibit prolonged lifespan, and mice are more resistant to diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistic studies demonstrate thatCdkn2apromotes the expression and activity of BECN1 by directly binding to its mRNA and its negative regulator BCL2L1, activating autophagy and accelerating the beige-to-white transition. Notably, reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced byCdkn2a-ablation. Furthermore, hyperactive BECN1 alone significantly accelerates the beige-to-white transition. Collectively, these findings show thatCdkn2a-mediated autophagy serves as a brake system for beige adipocyte maintenance and is a highly promising target for anti-obesity and anti-diabetes therapy.HighlightsCdkn2aablation promotes beige fat maintenance and ameliorates diet-induced obesityLoss ofCdkn2aretains beige adipocytes by inhibiting BECN1-mediated autophagyCdkn2amodulates BECN1 by binding to its mRNA and its inhibitor BCL2L1, respectivelyHyperactive BECN1 is sufficient to accelerate the beige-to-white transition
CRISPR prime editing for unconstrained correction of oncogenicKRASvariants
Authors: Jang Gayoung , Kweon Jiyeon , Kim Yongsub 
Published: December 2022

ABSTRACTKRASis the most commonly mutated RAS family gene and is a primary cause of the occurrence of several types of cancer. However,KRASmutations have several unique and diverse molecular identities, making it difficult to find specific treatments. Here, we developed universal pegRNAs which can correct all types of G12 and G13 oncogenicKRASmutations with CRISPR-mediated prime editors (PEs). The universal pegRNAs were found to be capable of correcting 12 types ofKRASmutations, accounting for 94% of all knownKRASmutations. Using our PE system, we successfully corrected 12 types ofKRASmutations with up to 54.7 % correction efficiency in HEK293T/17 cells. We also applied the universal pegRNA to correct endogenousKRASmutations in pancreatic cancer cells and found that G12V and G12DKRASmutations were successfully corrected to wild-typeKRASsequences with up to 18.7% correction efficiency without unwanted mutations. We propose prime editing with the universal pegRNA as a ‘one–to–many’ potential therapeutic strategy forKRASoncogene variants.