bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Proteomic Prognostic Markers for Alzheimer’s Disease with Survival Machine Learning: the Framingham Heart Study
Authors: Leng Yuanming , Ding Huitong , Ang Ting Fang Alvin , Au Rhoda , Doraiswamy P. Murali , Liu Chunyu 
Published: September 2024

AbstractBackgroundProtein abundance levels, sensitive to both physiological changes and external interventions, are useful for assessing the Alzheimer’s disease (AD) risk and treatment efficacy. However, identifying proteomic prognostic markers for AD is challenging by their high dimensionality and inherent correlations.MethodsOur study analyzed 1128 plasma proteins, measured by the SOMAscan platform, from 858 participants 55 years and older (mean age 63 years, 52.9% women) of the Framingham Heart Study (FHS) Offspring cohort. We conducted regression analysis and machine learning models, including LASSO-based Cox proportional hazard regression model (LASSO) and generalized boosted regression model (GBM), to identify protein prognostic markers. These markers were used to construct a weighted proteomic composite score, the AD prediction performance of which was assessed using time-dependent area under the curve (AUC). The association between the composite score and memory domain was examined in 339 (of the 858) participants with available memory scores, and in an independent group of 430 participants younger than 55 years (mean age 46, 56.7% women).ResultsOver a mean follow-up of 20 years, 132 (15.4%) participants developed AD. After adjusting for baseline age, sex, education, and APOE ε4+ status, regression models identified 309 proteins (P≤ 0.2). After applying machine learning methods, nine of these proteins were selected to develop a composite score. This score improved AD prediction beyond the factors of age, sex, education, and APOE ε4+ status across 15 to 25 years of follow-up, achieving its peak AUC of 0.84 in the LASSO model at the 22-year follow-up. It also showed a consistent negative association with memory scores in 339 participants (beta = -0.061,P= 0.046), 430 independent participants (beta = -0.060,P= 0.018), and the pooled 769 samples (beta = -0.058,P= 0.003).ConclusionThese findings highlight the utility of proteomic markers in improving AD prediction and emphasize the complex pathology of AD. The composite score may aid early AD detection and efficacy monitoring, warranting further validation in diverse populations.
Morphology-based classification of sickle cell disease and β-thalassemia using a low-cost automated microscope and machine learning
Authors: Shrestha Pranav , Lohse Hendrik , Bhatla Christopher , McCartney Heather , Alzaki Alaa , Sandhu Navdeep , Oli Pradip Kumar , Li Hongquan , Prakash Manu , Amid Ali , Onell Rodrigo , Au Nicholas , Merkeley Hayley , Kapoor Videsh , Pande Rajan , Stoeber Boris 
Published: September 2024

AbstractSickle cell disease (SCD) and β-thalassemia are the most common monogenic diseases, disproportionately affecting low- and middle-income countries, where low-cost and accurate diagnostic tools are needed to reduce the global disease burden. Although the sickling test is commonly used to screen for the sickle mutation, it cannot distinguish between the asymptomatic sickle cell trait (SCT) and SCD, or identify β-thalassemia. Here, we enhanced the inexpensive sickling test using automated microscopy and morphology-based machine learning classification to detect SCD, trait conditions (SCT and β-thalassemia trait) and normal individuals with an overall area under receiver operating curve, sensitivity and specificity of 0.940 (95% confidence intervals: 0.938-0.942), 84.6% (84.2%-84.9%), and 92.3% (92.1%-92.4%), respectively. Notably, the sensitivity and specificity to detect severe disease (SCD) was over 97% and 98%, respectively, thus establishing a low-cost automated screening option for disease detection in low-resource settings. Furthermore, leveraging high-throughput microscopy, we generated an open-access dataset comprising over 300,000 images with 1.5 trillion segmented cells from 138 individuals in Canada and Nepal including individuals with sickle and/or β-thalassemia mutations, to accelerate further research.
The Effect of Firearm Laws on Pediatric Mortality in the United States
Authors: Faust Jeremy Samuel , Chen Ji , Bhat Shriya , Otugo Onyekachi , Renton Benjamin , Chen Alexander Junxiang , Lin Zhenqiu , Krumholz Harlan M. 
Published: September 2024

AbstractIntroductionFirearms are the leading cause of death in US children and adolescents, but little is known about whether legal policies may be responsible.MethodsWe conducted difference-in-differences analysis on CDC WONDER data before and afterMcDonald v. Chicago, the landmark 2010 Supreme Court decision on firearms regulation. States were divided into three groups, based on legal actions taken before and since 2010, most permissive, permissive, and restricted. Firearm mortality trends before (1999-2010) and after (2010-2023) were determined and compared across the three groups for all intents and by intent (homicide and suicide). Within the most permissive state grouping, pediatric firearm mortality by 2013 urbanicity and by observed race and ethnicity were conducted. For each US state, pre-and- post 2010 all-intent pediatric firearm mortality incident rates were compared.ResultsThere were 7130 excess pediatric firearms deaths in states with more permissive regulatory regimes than those with stricter frameworks, as well as higher rates of homicide and suicide. Non-Hispanic Black populations were disproportionately affected by these trends. Four states (California, Maryland, New York, and Rhode Island) had decreased pediatric firearm mortality after 2010, all of which were in the restrictive firearms law group.ConclusionStates with more permissive firearm laws have experienced greater pediatric firearm mortality during the post-McDonald v. Chicagoera.KEY POINTSQuestionDid states enacting permissive firearm laws after 2010—whenMcDonald v. Chicagowas decided by the United States Supreme Court—subsequently experience higher rates of pediatric firearm mortality?FindingsDifference-in-difference analysis found that state groups that enacted more permissive firearm laws after 2010 experienced >7,100 firearm deaths in children and adolescents ages 0-17 between 2010-2023 compared to restrictive law-enacting states, of which most (77.5%) were homicides. In the permissive states groups, increases occurred in all urbanicities. The largest increase occurred in non-Hispanic Black children and adolescents. Four states had statistical decreases in pediatric firearm mortality during the study period, all of which were in states which enacted restrictive firearm policies.MeaningPermissive firearm laws contributed thousands of excess firearm deaths among children living in states with permissive policies. Future work should focus on determining which types of laws conferred the most harm and which the most protection.
Assessing the antimicrobial activity ofAframomum melegueta and Piper guineenseextract on pathogens of rot diseases of cucumber fruit
Authors: Akpan Patience Saturday , Umoren Eyoanwan Offon , William Ebere Ifiokobong , Ibuot Aniefon Alphonsus 
Published: September 2024

AbstractThe inhibitory potential ofAframomum melegueta and Piper guineenseextract against the pathogens of fruit rot diseases of cucumber was assessed. Two fungal isolates isolated from rotten cucumber fruits were;Fusarium oxysporiumandPenicilliumsp. The test plant extract were prepared in concentrations of 100% and 70%. The antimicrobial potential of ethanolic extract ofPiper guineenseat 100% concentration againstFusarium oxysporiumrevealed inhibition zone of 26.6 mm while 70% concentration of same plant extract had 17.0 mm. Ethanolic plant extract ofA. meleguetaat 100% concentration showed 7.5 mm and 70% concentration of same plant extract had 6.5 mm. Aqueous plant extract of both plants showed very minimal inhibitory effect onF. oxysporiumwhich ranged from 0.00mm to 8.5mm. ForPenicilliumsp, ethanolic extract ofPiper guineenseat 100% showed inhibition of 18.0mm and at 70% concentration of same plant extract showed inhibition of 12.5mm. Ethanolic plant extract ofA. meleguetaat 100% concentration inhibited the growth ofPenicilliumsp with inhibition zone of 15.5mm and the 70% concentration of same plant extract showed 11.5mm inhibition zone. The aqueous plant extract at 100% revealed inhibition zone of 15.5 mm and 70% concentration showed no inhibition. The phytochemical screening of test plants revealed the presence of most of the phytochemicals tested in abundance with very few exception.
Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity
Authors: Gangal Himanshu , Iannucci Jaclyn , Huang Yufei , Chen Ruifeng , Purvines William , Davis W. Taylor , Rivera Arian , Johnson Giles , Xie Xueyi , Mukherjee Sanjib , Vierkant Valerie , Mims Kaley , O’Neill Katherine , Wang Xuehua , Shapiro Lee A. , Wang Jun 
Published: September 2024

AbstractTraumatic brain injury (TBI) is a global health challenge, responsible for 30% of injury-related deaths and significantly contributing to disability. Annually, over 50 million TBIs occur worldwide, with most adult patients at emergency departments showing alcohol in their system. TBI is also a known risk factor for alcohol abuse, yet its interaction with alcohol consumption remains poorly understood. In this study, we demonstrate that the fluid percussion injury (FPI) model of TBI in mice significantly increases alcohol consumption and impairs cognitive function. At cellular levels, FPI markedly reduced the number and activity of striatal cholinergic interneurons (CINs) while increasing microglial cells. Notably, depleting microglial cells provided neuroprotection, mitigating cholinergic loss and enhancing cholinergic activity. These findings suggest that TBI may promote alcohol consumption and impair cognitive abilities through microglia activation and consequently reduced cholinergic function. Our research provides critical insights into the mechanisms linking TBI with increased alcohol use and cognitive deficits, potentially guiding future therapeutic strategies.
Field-crop transcriptome models are enhanced by measurements in systematically controlled environments
Authors: Hashida Yoichi , Kyogoku Daisuke , Tanaka Suguru E. , Mori Naoya , Tanabata Takanari , Watanabe Hiroyuki , Nagano Atsushi J. 
Published: September 2024

AbstractPlants in the field respond to seasonal and diel changes in various environmental factors such as irradiance and temperature. We previously developed a statistical model that predicts rice gene expression from the meteorological data and identified the environmental factors regulating each gene. However, since irradiance and temperature (the two most critical environmental factors) are correlated in the field, it remains difficult to distinguish their roles in gene expression regulation. Here, we show that transcriptome dynamics in the field are predominantly regulated by irradiance, by the modelling involving diurnal transcriptome data from the 73 controlled conditions where irradiance and temperature were independently varied. The model’s prediction performance is substantially high when trained using field and controlled conditions data. Our results highlight the utility of a systematic sampling approach under controlled environments to understand the mechanism of plant environmental response and to improve transcriptome prediction under field environments.
Proteomic responses of oat (Avena sativaL.) to drought stress
Authors: Chen Caijin , Bao Mingfang , Zeng Yanxia , Wang Xuemin , Liu Wenhui 
Published: September 2024

AbstractDrought is a major abiotic factor limiting the growth and development of the oat industry, and understanding its drought tolerance mechanisms is vital to oat production. In this study, we measured the phenotypic and physiological indices of drought-resistant (Grain King [G]) and water-sensitive (XiYue [X]) oat varieties and performed comparative proteomic analysis under drought stress and normal water supply (soil water content of 75% ± 5% of field water holding capacity) conditions. The results indicated that plant height, aboveground biomass, and underground biomass of variety X were 7.9%, 9.5%, and 14.6% lower than those under normal water supply, respectively, and the difference in plant height was significant (p< 0.05), whereas the decrease in all these indicators of variety G was small. Drought stress significantly increased malondialdehyde (MDA) content, soluble sugar (SS) content, superoxide dismutase (SOD) activity, and peroxidase (POD) activity of variety G by 48.6%, 68.5%, 81.3%, and 101.7%, respectively (p< 0.05). Variety X also showed increases up to various extents, but the increases were smaller than those of variety G. Additionally, 151 and 792 differentially expressed proteins (DEPs) identified in varieties G and X, respectively. Weighted Gene Co-expression Network Analysis(WGCNA), Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genome(KEGG) analyses demonstrated that the DEPs who were highly correlated with POD and SOD activity and SS content in variety G, were majorly involved in energy metabolism, protein translation, RNA processing, amino acid metabolism, and protein folding, whereas those with high correlation with the above three physiological indicators in variety X were primarily involved in RNA processing, protein stabilization, plant photosynthesis, intracellular signal transduction, and protein folding. Overall, the study elucidated the drought resistance mechanisms of different types of oats at the protein level。
Postpartum Depression During the COVID-19 Pandemic and Associated Factors: A Cross-Sectional Study
Authors: Teruya Mariana Mie , Carrijo Gabriel Sant’Ana , Moraes Costa Gleise Aparecida , Da Silva Mariliza Henrique , Targa de Lima Júlia Ribeiro , Sacramento Veltri Costa Julia Fontanezzi , Strufaldi Rodolfo , Sobrinho Valete Cristina Ortiz 
Published: September 2024

AbstractObjectiveTo study the prevalence of maternal depressive symptoms in the immediate postpartum period (≤ 7 days postpartum) during the COVID-19 pandemic and to identify associated factors.MethodsWe performed a cross-sectional analytical study. The study population consisted of postpartum women >18 years old enrolled at the Municipal University Hospital of São Bernardo do Campo. The Edinburgh Postnatal Depression Scale and a questionnaire on sociodemographic characteristics and clinical history were administered to 90 patients in the first week of the immediate postpartum period between June and December 2021.ResultsAn Edinburgh Postnatal Depression Scale score > 10 was observed in 39 (43.3%) of the postpartum women. From a multivariate analysis, the factors associated with a score > 10 on the scale were: “having no belief/spirituality” with 83% (95% CI 1.20-2.81, p<0.006), “having had more than one pregnancy” with 50% (95% CI 0.29-0.89, p<0.02), “having a previous episode of depression” with 64% (95% CI 1.02-2.65, p<0.04), and “having a previous episode of anxiety” with 83% (95% CI 1.06-3.16, p<0.03). The other factors studied did not have statistical significance.ConclusionWith the COVID-19 pandemic, an increase in the prevalence of depressive symptoms in the immediate postpartum period was observed. The postpartum women who scored > 10 on the EPDS had the following common associated factors: “having no belief/spirituality”, “having had more than one pregnancy”, “having a previous episode of depression”, and “having a previous episode of anxiety”. These findings indicate the need for greater attention from health professionals to these positive factors.
One Health assessment of poultry and cattle farms as reservoirs for ESBL-producingEscherichia coli
Authors: Malik Hina , Singh Randhir , Kaur Simranpreet , Parmar Neha , Tyagi Anuj , Aulakh R. S. , Gill J.P.S. 
Published: September 2024

ABSTRACTBACKGROUNDUnregulated use of antibiotics in animal food production leads to the emergence of multidrug resistant bacteria, notably extended-spectrum beta-lactamases producingEscherichia coli(ESBLE. coli). ESBLs severely limit treatment options and pose a significant threat to public health. Investigating the potential role of livestock and poultry farms in harboring ESBLE. coliis crucial, given the prevalence of ESBLE. coliin humans, animals, and the environment, following the One Health framework.OBJECTIVESThe aim of this study was to assess and compare the potential contribution of cattle and poultry farms along with their respective human handlers to the emergence and spread of ESBLE. colifollowing One Health approach.METHODSTwenty cattle and twenty poultry farms were surveyed in Ludhiana, India to determine antibiotic usage, prevalent diseases in the farms. Animal faeces/poultry droppings, handler hand swabs, and stool samples were examined for the presence of ESBLE. coli. The isolates were examined for their susceptibility to 16 antibiotics and for the presence of selected antimicrobial resistance genes, including ESBL genes. Generalized linear mixed models were applied to investigate variations in the prevalence of ESBLE. coliassociated with farm animal species, farm practices, and farm biosecurity measures.RESULTSOur findings revealed a higher prevalence of ESBLE. coliin poultry farms (53.75%) than in cattle farms (40.72%) and overall lower prevalence (12%) in human handlers. Of the total isolates, 86.52% were multidrug resistant, and 93.91% showed a high multiple antibiotic resistance (MAR) index (>0.2). Isolates from poultry farms exhibited a higher level of resistance with 97% of isolates exhibiting multidrug resistance, 100% isolates with MAR index of more than 0.2, and 90.70% carrying theblaCTXMgene.CONCLUSIONOur findings highlight cattle and poultry farms as potential reservoirs for multidrug-resistant and ESBLE. coli, contributing to the rising environmental burden of antibiotic resistance genes. This emphasizes the urgency of limiting antibiotic use in animal farming, especially in poultry production, to address the escalating problem of antibiotic resistance and protect both animal and human health.
PHluorin-conjugated secondary nanobodies as a tool for measuring synaptic vesicle exo- and endocytosis
Authors: Georgiev Svilen V. , Rizzoli Silvio O. 
Published: September 2024

AbstractNeuronal communication relies on synaptic vesicle recycling, which has long been investigated by live imaging approaches. Synapto-pHluorins, genetically encoded reporters that incorporate a pH-sensitive variant of GFP within the lumen of the synaptic vesicle, have been especially popular. However, they require genetic manipulation, implying that a tool combining their excellent reporter properties with the ease of use of classical immunolabeling would be desirable. We introduce this tool here, relying on primary antibodies against the luminal domain of synaptotagmin 1, decorated with secondary single-domain antibodies (nanobodies) carrying a pHluorin moiety. The application of the antibodies and nanobodies to cultured neurons results in labeling their recycling vesicles, without the need for any additional manipulations. The labeled vesicles respond to stimulation, in the expected fashion, and the pHluorin signals enable the quantification of both exo- and endocytosis. We conclude that pHluorin-conjugated secondary nanobodies are a convenient tool for the analysis of vesicle recycling.
PointTree: Automatic and accurate reconstruction of long-range axonal projections of single-neuron
Authors: Cai Lin , Fan Taiyu , Qu Xuzhong , Zhang Ying , Gou Xianyu , Ding Quanwei , Feng Weihua , Cao Tingting , Lv Xiaohua , Liu Xiuli , Huang Qing , Quan Tingwei , Zeng Shaoqun 
Published: September 2024

AbstractSingle-neuron axonal projections reveal the route map of neuron output and provide a key cue for understanding how information flows across the brain. Reconstruction of single-neuron axonal projections requires intensive manual operations in tens of terabytes of brain imaging data, and is highly time-consuming and labor-intensive. The main issue lies in the need for precise reconstruction algorithms to avoid reconstruction errors, yet current methods struggle with densely distributed axons, focusing mainly on skeleton extraction. To overcome this, we introduce a point assignment-based method that uses cylindrical point sets to accurately represent axons and a minimal information flow tree model to suppress the snowball effect of reconstruction errors. Our method successfully reconstructs single-neuron axonal projections across hundreds of GBs images with an average of 80% F1-score, while current methods only provide less than 40% F1-score reconstructions from a few hundred MBs images. This huge improvement is helpful for high-throughput mapping of neuron projections.
Examination of low-intensity focused ultrasound parameters for human neuromodulation
Authors: Ennasr Areej , Isaac Gabriel , Strohman Andrew , Legon Wynn 
Published: September 2024

ABSTRACTBackgroundLow-intensity focused ultrasound (LIFU) is a promising form of non-invasive neuromodulation characterized by a rich parameter space that includes intensity, duration, duty cycle and pulsing strategy. The effect and interaction of these parameters to affect human brain activity is poorly understood. A better understanding of how parameters interact is critical to advance LIFU as a potential therapeutic.Objective/HypothesisTo determine how different parameters, including intensity, duration, and duty cycle interact to produce neuromodulation effects in the human brain. Further, this study assesses the effect of pulsing versus continuous ultrasound. We hypothesize that higher duty cycles will confer excitation. Increasing intensity or duration will increase the magnitude of effect. Pulsing LIFU will not be more effective than continuous wave ultrasound.MethodsN = 18 healthy human volunteers underwent 20 different parameter combinations that included a fully parametrized set of two intensities (ISPPA: 6 & 24 W/cm2), five duty cycles (1, 10, 30, 50, 70%) and two durations (100, 500 msec) with a constant pulse repetition frequency of 1 kHz delivered concurrently with transcranial magnetic stimulation (TMS) to the primary motor cortex (M1). Four of these parameter combinations were also delivered continuously, matched on the number of cycles. Motor-evoked potential (MEP) amplitude was the primary outcome measure. All parameter combinations were collected time-locked to MEP generation.ResultsThere was no evidence of excitation from any parameter combination. 3 of the 24 parameter sets resulted in inhibition. The parameter set that resulted in the greatest inhibition (∼ 30%) was an intensity of 6W/cm2with a duty cycle of 30% and a duration of 500 msec. A three-way ANOVA revealed an interaction of intensity and duty cycle. The analysis of continuous versus pulsed ultrasound revealed a 3-way interaction of intensity, pulsing, and the number of cycles such that under the 6W/cm2condition higher cycles of pulsed ultrasound resulted in inhibition whereas lower number of cycles using continuous LIFU resulted in inhibition.ConclusionsLIFU to M1 in humans, in the range employed, either conferred inhibition or had no effect. Significant excitation was not observed. In general, lower intensity looks to be more efficacious for inhibition that depends on duration. Finally, pulsed ultrasound looks to be more effective for inhibition as compared to continuous wave after controlling for total energy delivered.