bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of future chronic hypertension from maternal characteristics in early pregnancy
Authors: Charakida Marietta , Wright Alan , Magee Laura A , Syngelaki Argyro , von Dadelszen Peter , Akolekar Ranjit , Wright David , Nicolaides Kypros H 
Published: May 2023

ABSTRACTBackgroundPre-eclampsia (PE) and gestational hypertension (GH) identify women at increased risk of chronic hypertension (CH) and cardiovascular disease, but as efforts to prevent PE and GH advance, fewer women at increased cardiovascular risk will be identified.MethodsCohort of 26,511 women seen in two consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure (BP) at 11-13 weeks’ gestation, and development of PE or GH in the index pregnancy. Logistic regression models were fitted for prediction of development of future CH by the 20thweek of the subsequent pregnancy. Performance of screening and risk calibration of the model were assessed.Results1560 (5.9%) women developed PE or GH (index pregnancy), and 215 (0.8%) developed future CH, a median of 3.0 years later. Predictors from the index pregnancy of development of future CH were: early pregnancy maternal age, weight and BP; Black or South Asian ethnicity; family history of PE; parity; and development of PE or GH. PE or GH accounted for 52.1% (95% confidence interval 45.2-58.9%) of future CH. At a screen-positive-rate of 10%, a model including terms for maternal characteristics and early pregnancy BP accounted for 67.9% (61.2-74.5) of future CH; addition of the development of PE or GH detected 73.5% (67.1-79.3) of future CH. Risks produced from the predictive model were well-calibrated and confirmed by five-fold cross-validation.ConclusionEarly maternal characteristics and BP are effective in predicting development of future CH. As new interventions are expected to reduce the occurrence of PE and GH, our study results offer an alternative strategy for identifying women at increased risk of future CH and are applicable worldwide.
Zika Virus looming epidemic in Pakistan: seroprevalence findings by plaque reduction neutralization test in the Sindh Region of Pakistan
Authors: Imtiaz Khekashan , Farooqi Joveria , Barr Kelli L. , Kanji Akbar , Prakoso Dhani , Azizullah Zahida , Long Maureen T. , Khan Erum 
Published: May 2023

ABSTRACTBackgroundZika virus (ZIKV) has emerged as a cause of febrile illness in children and adults globally. West Asian and Middle Eastern countries have not yet experienced the widespread emergence of ZIKV. In Pakistan, detection of ZIKV antibodies have been reported. However, the validity of this data is questionable given the current understanding of flaviviral antigenic cross-reactivity. In order to determine if ZIKV is circulating in the Sindh region of Pakistan, patients presenting to healthcare centers with an acute febrile dengue-like illness were evaluated for ZIKV infection.MethodsDengue virus (DENV) screening in patients was performed using a commercial ELISA Rapid Test NS1 antigen capture test. All DENV negative samples were tested for Zika virus, using a commercial IgM capture ELISA kit. Additionally, a plaque reduction neutralization test (PRNT) was performed to measure neutralizing antibodies. Singleplex, two-step Real-time PCR using general primers and probes was performed for the detection of Zika virus nucleic acid.ResultsPatients with acute dengue-like illness (DLI) presenting at healthcare centers in different sites throughout the Sindh region of Pakistan were recruited. A total of 745 patient samples were tested for ZIKV via IgM ELISA and RT-PCR. Thirty-seven samples (4.9%) tested positive for ZIKV IgM without any cross-reactivity to other flaviviruses tested simultaneously. These were considered as presumptive positive for ZIKV, selected presumptive positive samples (n=20) were confirmed using PRNT50 using Vero cells. All 20 samples showed ZIKV neutralization at PRNT50.ConclusionsOur study provides evidence that ZIKV is circulating in the Sindh region of Pakistan and is a probable cause of clinical dengue-like illness (DLI) cases that are seen seasonally in Pakistan.
Deep brain stimulation in globus pallidus internus travels to thalamus and subthalamic nuclei along physiological pathways
Authors: Kasiri Maral , Vidmark Jessica , Hernandez-Martin Estefania , Mousavi S. Alireza Seyyed , Sanger Terence D. 
Published: May 2023

AbstractDeep brain stimulation (DBS) is a neuromodulation method for treatment of various neurological disorders. It is often assumed that the primary inhibition or excitation effect of DBS occurs at the site of stimulation. However, recent work has shown that DBS can lead to robust evoked potentials (EP) not only at the stimulation site, representing the local effect, but also in distant brain regions, representing the effects on distant targets. While the significance of these EPs for therapeutic outcomes is not known, it appears that the electrical effects of DBS have a partial modulatory impact on downstream targets. Nonetheless, it remains unclear through what mechanism DBS pulses travel to the distant targets or what portion of the pulses travel along the normal pathways from the stimulation site. The possible scenarios include orthodromic or antidromic pathways, accessory pathways, normally inhibited pathways, and direct electromagnetic activation of distant sites. The ability to record signals from brain regions provides an opportunity to determine the mechanism of DBS signal transmission. We hypothesize that the pathways that transmit DBS pulses include the pathways that transmit intrinsic neural signals. To test this, we performed a transfer function analysis on deep brain recordings during DBS-off condition and compared its impulse response with the transmission of signals from electrical stimulation during DBS-on condition. Our results support our claim that the electrical pulses travel partly along intrinsic neural pathways by showing that the propagation of DBS signals can be partially predicted by observation of intrinsic neural activity and measurement of DBS-EPs.New & noteworthyThis study enhances the understanding of deep brain stimulation (DBS) mechanism by exploring how electrical stimulation travels along neural pathways. We utilized a computational method to explain the main routes through which DBS pulses travel. Our results suggest that DBS signals are likely to be transmitted along the normal pathways. This provides a basis to develop complex and nonlinear models of brain and relate the modulatory effect of stimulation to the brain connectome.
Closing the accessibility gap to mental health treatment with a conversational AI-enabled self-referral tool
Authors: Habicht Johanna , Viswanathan Sruthi , Carrington Ben , Hauser Tobias , Harper Ross , Rollwage Max 
Published: May 2023

AbstractAccessing mental health care can be challenging, and minority groups often face additional barriers. This study investigates whether digital tools can enhance equality of access to mental health treatment. We evaluated a novel AI-enabled self-referral tool (a chatbot) designed to make entry to mental health treatment more accessible in a real-world setting.In a multi-site observational study, data were collected from 129,400 patients who referred to 28 separate NHS Talking Therapies services across England. Our results indicate that the tool led to a 15% increase in total referrals, which was significantly larger than the 6% baseline increase observed in matched services using traditional self-referral methods during the same time period. Importantly, the tool was particularly effective for minority groups, which included non-binary (235% increase), bisexual (30% increase), and ethnic minority individuals (31% increase). This paints a promising picture for the use of AI chatbots in mental healthcare and suggests they may be especially beneficial for demographic groups that experience barriers to accessing treatment in the traditional care systems.To better understand the reasons for this disproportional benefit for minority groups, we used thematic analysis and Natural Language Processing (NLP) models to evaluate qualitative feedback from 42,332 individuals who referred through the AI-enabled tool. We found that the tool’s human-free nature and its ability to improve the perceived need for treatment were the main drivers for improved diversity.These findings suggest that AI-enabled chatbots have the potential to increase accessibility to mental health services for all, and to alleviate barriers faced by disadvantaged populations. The results have important implications for healthcare policy, clinical practice, and technology development.
Extraction and Reduction of the Parameters of Archimedes Spirals Drawn by Patients
Authors: Khan Furrukh , Xiaoxi Jessie , Dalm Brian , Thomas Evan 
Published: May 2023

AbstractAnalysis of patient’s hand drawn Archimedes spirals is commonly used in the medical community to grade various forms of tremors. These spirals are often drawn on paper using a pen or a pencil and then Xeroxed/scanned to turn the drawings into computer images. This process introduces artifacts such as misalignment of the paper, finite/variable width of the drawn line, light grey marks left by the toner, and greyscale background pixels introduced by the Xeroxing/scanning steps. Even a spiral drawn directly on the screen of a tablet produces lines with multi-pixel widths and varying greyscale values. These artifacts make it difficult to use image processing techniques to automatically extract the patient’s spiral as a clean single-valued discrete signal which could be treated mathematically for further analysis. We present a procedure in this paper to extract the patient’s hand-drawn spiral automatically as a mathematical discrete signal even in the presence of artifacts, with minimal user intervention. We also note that the spirals used by some hospitals and clinics are distorted and not perfect Archimedes spirals; nevertheless, our procedure can still be used for these cases. The extracted discrete signal is composed of a couple of thousand samples (features). The largeness of this feature space compared with the typical number of spiral samples at our disposal (of the order of only hundreds) makes it infeasible to apply Machine Learning techniques for predictions which generalize well in the real world without overfitting. We analyze the extracted discrete signal using FFT (Fast Fourier Transforms) and show that in FFT space the signal can be represented by as few as 300 parameters. The paper concludes that if these 300 parameters (or even 150 parameters for some problems) are used as a feature set for Machine Learning then it could very well be possible to make predictions which generalize well to the real world without overfitting. As a note, applications to actual Machine Learning problems are not covered in this paper.
Comparing the risks of diabetes, psychological distress, and radiation-induced cancer exposure after the Fukushima disaster using the loss of happy life expectancy
Authors: Murakami Michio , Ozaki Akihiko , Ono Kyoko , Nomura Shuhei , Takebayashi Yoshitake , Tsubokura Masaharu 
Published: May 2023

AbstractAfter disasters, direct deaths and secondary health effects, such as diabetes and psychological distress, can occur. It is critical to compare the magnitudes of these risks to promote effective public health measures. In this study, we used the loss of happy life expectancy (LHpLE) to compare the risks associated with diabetes, psychological distress, and radiation-induced cancer after the 2011 Fukushima disaster. Two questionnaire surveys were conducted on people affected by the disaster to investigate the potential associations between diabetes and psychological distress, as well as breast cancer and reduced emotional happiness, with 680 and 582 participants, respectively. Additionally, we calculated the LHpLE owing to these risks. Although no significant reduction was found in emotional happiness due to diabetes or breast cancer, a significant reduction occurred due to psychological distress (0.265 and 0.476 for males and females, respectively). In the population aged 40–74 years, the LHpLE due to radiation-induced cancer, diabetes, and psychological distress were 0.0013, 0.14, and 0.21 years, respectively. This suggests that the association of LHpLE with diabetes and psychological distress was over two orders of magnitude greater than that associated with radiation-induced cancer. Within 7 years following the disaster, LHpLE due to diabetes increased, highlighting that diabetes is an ongoing issue. Therefore, this novel indicator of the LHpLE can provide a foundation for promoting effective public health measures following disasters.
SIV clearance from neonatal macaques following transient CCR5 depletion
Authors: Deere Jesse D. , Merriam David , Leggat Kawthar Machmach , Chang Wen-Lan William , Méndez-Lagares Gema , Kieu Hung , Dutra Joseph , Fontaine Justin , Lu Wenze , Chin Ning , Chen Connie , Tran Bryant Chi-Thien , Salinas Jessica , Miller Corey N. , Deeks Steven G. , Lifson Jeffrey D. , Engelman Kathleen , Magnani Diogo , Reimann Keith , Stevenson Mario , Hartigan-O’Connor Dennis J. 
Published: May 2023

SUMMARY PARAGRAPHTreatment of people with HIV (PWH) with antiretroviral therapy (ART) results in sustained suppression of viremia, but HIV persists indefinitely as integrated provirus in CD4-expressing cells. Intact persistent provirus, the “rebound competent viral reservoir” (RCVR), is the primary obstacle to achieving a cure. Most variants of HIV enter CD4+T cells by binding to the chemokine receptor, CCR5. The RCVR has been successfully depleted only in a handful of PWH following cytotoxic chemotherapy and bone marrow transplantation from donors with a mutation inCCR5. Here we show that long-term SIV remission and apparent cure can be achieved for infant macaques via targeted depletion of potential reservoir cells that express CCR5. Neonatal rhesus macaques were infected with virulent SIVmac251, then treated with ART beginning one week after infection, followed by treatment with either a CCR5/CD3-bispecific or a CD4-specific antibody, both of which depleted target cells and increased the rate of plasma viremia decrease. Upon subsequent cessation of ART, three of seven animals treated with CCR5/CD3-bispecific antibody rebounded quickly and two rebounded 3 or 6 months later. Remarkably, the other two animals remained aviremic and efforts to detect replication-competent virus were unsuccessful. Our results show that bispecific antibody treatment can achieve meaningful SIV reservoir depletion and suggest that functional HIV cure might be achievable for recently infected individuals having a restricted reservoir.
Complement C3 reduces apoptosis in human cardiomyocytes
Authors: Fang Zhou , Li Xiang , Yang Fajun , Xiaoli Alus Michael , Zhang Ming 
Published: May 2023

AbstractComplement C3 is a key factor in complement system. Our recently animal study found that C3 may regulate myocardial apoptosis through the intrinsic apoptosis pathway. The current work investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Our results showed that incubation of exogenous C3 reduced apoptosis in a cell culture system of human cardiomyocytes which did not inherently express C3. In addition, C3 inhibited intrinsic apoptosis pathway in a cell-free apoptosis system. Furthermore, pro-C3 was found to bind with an apoptotic factor, pro-caspase 3, in a cell-free system. Thus, we presented firsthand evidence that exogenous C3 is readily reduce apoptosis in human cardiomyocytes via interaction with the intrinsic apoptotic pathway.
scDisInFact: disentangled learning for integration and prediction of multi-batch multi-condition single-cell RNA-sequencing data
Authors: Zhang Ziqi , Zhao Xinye , Qiu Peng , Zhang Xiuwei 
Published: May 2023

ABSTRACTSingle-cell RNA-sequencing (scRNA-seq) has been widely used for disease studies, where sample batches are collected from donors under different conditions including demographical groups, disease stages, and drug treatments. It is worth noting that the differences among sample batches in such a study are a mixture of technical confounders caused by batch effect and the biological variations caused by condition effect. However, current batch effect removal methods often eliminate both technical batch effects and meaningful condition effects, while perturbation prediction methods solely focus on condition effects, resulting in inaccurate gene expression predictions due to unaccounted batch effects.Here we introduce scDisInFact, a deep learning framework that models both batch effect and condition effect in scRNA-seq data. scDisInFact learns latent factors that disentangle condition effects from batch effects, enabling it to simultaneously perform three tasks: batch effect removal, condition-associated key gene detection, and perturbation prediction. We evaluated scDisInFact on both simulated and real datasets, and compared its performance to baseline methods for each task. Our results demonstrate that scDisInFact outperforms existing methods that focus on individual tasks, providing a more comprehensive and accurate approach for integrating and predicting multi-batch multi-condition single-cell RNA-sequencing data.
DrugMechDB: A Curated Database of Drug Mechanisms
Authors: Gonzalez-Cavazos Adriana Carolina , Tanska Anna , Mayers Michael D. , Carvalho-Silva Denise , Sridharan Brindha , Rewers Patrik A. , Sankarlal Umasri , Jagannathan Lakshmanan , Su Andrew I. 
Published: May 2023

AbstractComputational drug repositioning methods have emerged as an attractive and effective solution to find new candidates for existing therapies, reducing the time and cost of drug development. Repositioning methods based on biomedical knowledge graphs typically offer useful supporting biological evidence. This evidence is based on reasoning chains or subgraphs that connect a drug to disease predictions. However, there are no databases of drug mechanisms that can be used to train and evaluate such methods. Here, we introduce the Drug Mechanism Database (DrugMechDB), a manually curated database that describes drug mechanisms as paths through a knowledge graph. DrugMechDB integrates a diverse range of authoritative free-text resources to describe 4,583 drug indications with 32,249 relationships, representing 14 major biological scales. DrugMechDB can be employed as a benchmark dataset for assessing computational drug repurposing models or as a valuable resource for training such models.
PACAP-mediated gating of anxiety-controlling circuits
Authors: Li Yan , Andero Raül , Luchkina Natalia V. , Suh Junghyup , Ross Rachel A. , Lowell Bradford B. , Carlezon William A. , Ressler Kerry J. , Bolshakov Vadim Y. 
Published: May 2023

AbstractCombining the use ofex vivoandin vivooptogenetics, viral tracing, electrophysiology and behavioral testing, we show that the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) gates anxiety-controlling circuits by differentially affecting synaptic efficacy at projections from the basolateral amygdala (BLA) to two different subdivisions of the dorsal subdivision of the bed nucleus of the stria terminalis (BNST), modifying the signal flow in BLA-ovBNST-adBNST circuits in such a way that adBNST is inhibited. Inhibition of adBNST is translated into the reduced firing probability of adBNST neurons during afferent activation, explaining the anxiety-triggering actions of PACAP in BNST, as inhibition of adBNST is anxiogenic. Our results reveal how innate, fear-related behavioral mechanisms may be controlled by neuropeptides, PACAP specifically, at the level of underlying neural circuits by inducing long-lasting plastic changes in functional interactions between their different structural components.
A computational model of the DNA damage-induced IKK/ NF-κB pathway reveals a critical dependence on irradiation dose and PARP-1
Authors: Konrath Fabian , Willenbrock Michael , Busse Dorothea , Scheidereit Claus , Wolf Jana 
Published: May 2023

SummaryThe activation of IKK/ NF-κB by genotoxic stress is a crucial process in the DNA damage response. Due to the anti-apoptotic impact of NF-κB it can affect cell fate decisions upon DNA damage and therefore interfere with tumour therapy-induced cell death. Here, we developed a dynamical model describing IKK/ NF-κB signalling that faithfully reproduces quantitative time course data and enabled a detailed analysis of pathway regulation. The approach elucidates a pathway topology with two hubs, where the first integrates signals from two DNA damage sensors and the second forms a coherent feedforward loop. The analyses reveal a critical role of the sensor protein PARP-1 in the pathway regulation. Introducing a method for calculating the impact of individual components on pathway activity in a time-resolved manner we show how irradiation dose influences pathway activation. Our results give a mechanistic understanding relevant for the interpretation of experimental and clinical studies.
Sperm regulates locomotor activity ofC. eleganshermaphrodites
Authors: Suo Satoshi 
Published: May 2023

AbstractSex differences in sex-shared behavior are common across various species. During mating, males transfer sperm and seminal fluid to females, which can affect female behavior. Sperm can be stored in the female reproductive tract for extended periods of time. However, its role in regulating female behavior is poorly understood. In the androdioecious nematodeC. elegans, hermaphrodites produce both egg cells and sperm, enabling them to self-fertilize or mate with males. Hermaphrodites exhibit less locomotor activity compared to males, indicating sex difference in behavioral regulation. In this study, sperm-deficient mutants were examined to investigate the role of sperm in the regulation of locomotor behavior. The results suggest that sperm plays a significant role in regulating sex-shared behavior inC. elegans, as sperm-deficient mutants exhibited increased locomotor activity. Additionally, females of closely related gonochoristic species,C. remaneiandC. brenneri, exhibited reduced locomotor activity after mating. The regulation of locomotion by sperm may be an adaptive mechanism that enables sperm-less hermaphrodites to search for mates and allow females to cease their search for mates after mating.