bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of climatic variables on dengue incidence in Cali
Authors: Frieri Mauricio , Gordillo Marisol , Sepúlveda Lilian S. 
Published: May 2024

AbstractIn this work we studied the relationship between dengue incidence in Cali and the climatic variables that are known to have an impact on the mosquito and were available (precipitation, relative humidity, minimum, mean, and maximum temperature). Since the natural processes of the mosquito imply that any changes on climatic variables need some time to be visible on the dengue incidence, a lagged correlation analysis was done in order to choose the predictor variables of count regression models. A Principal Component Analysis was done to reduce dimensionality and study the correlation among the climatic variables. Finally, aiming to predict the monthly dengue incidence, three different regression models were constructed and compared using de Akaike information criterion. The best model was the negative binomial regression model, and the predictor variables were mean temperature with a 3-month lag and mean temperature with a 5-month lag as well as their interaction. The other variables were not significant on the models. And interesting conclusion was that according to the coefficients of the regression model, a 1°C increase in the monthly mean temperature will reflect as a 45% increase in dengue incidence after 3 months. The rises to a 64% increase after 5 months.Author SummaryDengue is transmitted by the bite of an infected mosquito, and mosquitoes, in turn, are affected by climatic conditions. In this work studied the relationship between dengue incidence in Cali and climatic variables, namely precipitation, relative humidity, minimum temperature, mean temperature, and maximum temperature using statistical methods. Since this is a natural and biological process, the changes in climatic conditions need time to have a visible effect on dengue incidence, hence we identified the significant climatic variables and the time they take to have a visible effect on dengue incidence. Then, we created three different models for predicting dengue incidences using the lagged variables and picked the best one. We concluded that the most critical variable is mean temperature with a 3- and 5-month lag. We also found that a 1°C increase in the monthly mean temperature will reflect as a 45% increase in dengue incidence after 3 months. The rises to a 64% increase after 5 months.
Evaluating a Large Language Model’s Ability to Answer Clinicians’ Requests for Evidence Summaries
Authors: Blasingame Mallory N. , Koonce Taneya Y. , Williams Annette M. , Giuse Dario A. , Su Jing , Krump Poppy A. , Giuse Nunzia Bettinsoli 
Published: May 2024

AbstractObjectiveThis study investigated the performance of a generative artificial intelligence (AI) tool using GPT-4 in answering clinical questions in comparison with medical librarians’ gold-standard evidence syntheses.MethodsQuestions were extracted from an in-house database of clinical evidence requests previously answered by medical librarians. Questions with multiple parts were subdivided into individual topics. A standardized prompt was developed using the COSTAR framework. Librarians submitted each question into aiChat, an internally-managed chat tool using GPT-4, and recorded the responses. The summaries generated by aiChat were evaluated on whether they contained the critical elements used in the established gold-standard summary of the librarian. A subset of questions was randomly selected for verification of references provided by aiChat.ResultsOf the 216 evaluated questions, aiChat’s response was assessed as “correct” for 180 (83.3%) questions, “partially correct” for 35 (16.2%) questions, and “incorrect” for 1 (0.5%) question. No significant differences were observed in question ratings by question category (p=0.39). For a subset of 30% (n=66) of questions, 162 references were provided in the aiChat summaries, and 60 (37%) were confirmed as nonfabricated.ConclusionsOverall, the performance of a generative AI tool was promising. However, many included references could not be independently verified, and attempts were not made to assess whether any additional concepts introduced by aiChat were factually accurate. Thus, we envision this being the first of a series of investigations designed to further our understanding of how current and future versions of generative AI can be used and integrated into medical librarians’ workflow.
The COMT Val158Met Polymorphism is Significantly Associated with Early Onset Preeclampsia in Both African American and Caucasian Mothers
Authors: Kaufman Melissa R. , Hwang Amy E. , Pickrel Anthony M. , Gray Cassandra M. , Goel Kriti M. , Dhanraj David N. , Yaklic Jerome L. , Maxwell Rose A. , Brown Thomas L. 
Published: May 2024

AbstractThe aim of this study was to evaluate maternal and infant Val158Met polymorphisms of Catechol-O-Methyltransferase (COMT), a reported indicator of preeclamptic risk, in a United States population. Healthy control, early-onset preeclamptic, and late-onset preeclamptic patients were enrolled in this study. Genomic DNA was isolated from mothers and infants via buccal swabs and DNA was genotyped via tetra-primer amplification PCR. Our findings indicate that the COMT genotype was not significantly associated with late-onset PE. While there were no significant differences between African American and Caucasian races, the maternal COMTMet158Metgenotype was significantly associated with early-onset preeclampsia in both African Americans and Caucasians when compared to COMTVal158Valor COMTVal158Met. These results suggest that the maternal COMTMet158Metgenotype may be a risk factor for early-onset PE.
Assessment of knowledge and perception of prescribers towards rational medicine use in the Ashanti Region of Ghana
Authors: Djochie Richard Delali Agbeko , Owusu-Donkor Rita , d’Almeida Elizabeth Modupe , Akwah Francis Kwadwo Gyamfi , Kyeremateng Emmanuel , Opoku-Afriyie Samuel , Tabiri Cecilia Akosua , Frimpong Francis Kyei , Dwomoh Samuel , Yiadom Jonathan Boakye 
Published: May 2024

AbstractBackgroundPrescribers must possess extensive knowledge and maintain a positive attitude towards the rational use of medicines to achieve desirable treatment outcomes and effectively prevent treatment failures, increased costs, drug toxicities, and interactions. The objective of this study was to evaluate prescribers’ understanding and perception concerning the rational use of medicines in public hospitals. Additionally, the study aimed to identify the factors that influence rational prescribing practices.MethodsA structured data instrument was developed to collect demographic data and evaluate participants’ knowledge and perception of rational medicine use, in line with the study objectives. Chi-squared statistics and Fisher’s exact test were utilized to identify factors associated with good knowledge and perception among participants. Logistic regression was then employed to assess the strength of the associations, with odd ratios reported at a significant level of 0.05.ResultsOut of 192 participants, 85.4% held a positive view of rational medicine use, stressing patient safety and recognizing risks like antimicrobial resistance and polypharmacy. Perception was influenced by factors such as prescriber profession, access to references, and drug bulletin updates. Additionally, 65.6% demonstrated good knowledge of rational medicine use, which was notably influenced by factors like using standard prescribing guidelines, having a functional Drug and Therapeutics Committee, prescriber profession, and the frequency of drug bulletin updates.ConclusionThe study emphasizes the critical need to address knowledge gaps among healthcare professionals, especially nurses and other prescribers, to ensure the safe and effective use of medications. It highlights the positive influence of utilizing preferred prescribing references and the existence of functional Drug and Therapeutics Committees in hospitals on knowledge levels. However, the unexpected findings regarding the limited impact of frequent updates of drug bulletins require further investigation.
Genomic sequencing surveillance of patients colonized with vancomycin-resistantEnterococcus(VRE) improves detection of hospital-associated transmission
Authors: Sundermann Alexander J. , Rangachar Srinivasa Vatsala , Mills Emma G. , Griffith Marissa P. , Evans Eric , Chen Jieshi , Waggle Kady D. , Snyder Graham M. , Pless Lora Lee , Harrison Lee H. , Van Tyne Daria 
Published: May 2024

ABSTRACTBackgroundVancomycin-resistant enterococcal (VRE) infections pose significant challenges in healthcare. Transmission dynamics of VRE are complex, often involving patient colonization and subsequent transmission through various healthcare-associated vectors. We utilized a whole genome sequencing (WGS) surveillance program at our institution to better understand the contribution of clinical and colonizing isolates to VRE transmission.MethodsWe performed whole genome sequencing on 352 VRE clinical isolates collected over 34 months and 891 rectal screening isolates collected over a 9-month nested period, and used single nucleotide polymorphisms to assess relatedness. We then performed a geo-temporal transmission analysis considering both clinical and rectal screening isolates compared with clinical isolates alone, and calculated 30-day outcomes of patients.ResultsVRE rectal carriage constituted 87.3% of VRE acquisition, with an average monthly acquisition rate of 7.6 per 1000 patient days. We identified 185 genetically related clusters containing 2-42 isolates and encompassing 69.6% of all isolates in the dataset. The inclusion of rectal swab isolates increased the detection of clinical isolate clusters (from 53% to 67%, P<0.01). Geo-temporal analysis identified hotspot locations of VRE transmission. Patients with clinical VRE isolates that were closely related to previously sampled rectal swab isolates experienced 30-day ICU admission (17.5%), hospital readmission (9.2%), and death (13.3%).ConclusionsOur findings describe the high burden of VRE transmission at our hospital and shed light on the importance of using WGS surveillance of both clinical and rectal screening isolates to better understand the transmission of this pathogen. This study highlights the potential utility of incorporating WGS surveillance of VRE into routine hospital practice for improving infection prevention and patient safety.
From Necessity to Preference: A Study of Predictors Influencing Elective Caesarean Section in Rwanda
Authors: Koray Munawar Harun , Dushimirimana Theophile , Curry Tanya , Adupo Katia Olaro , Faabie Alfred Pie , Punguyire Damien 
Published: May 2024

AbstractBackgroundCaesarean section is an important obstetric intervention that saves the lives of mother and newborn babies. However, its increase is of global public health concern. Despite tremendous reduction in maternal and newborn morbidity and mortality, Rwanda has shown a very high incidence of CS among mothers in recent years. Therefore, this study investigated the predictors of patient-initiated elective CS in Rwanda.MethodsIn this cross-sectional study, we used nationally representative data from Rwanda Demographic and Health Survey 2019/20. A total of 6,167 females were included in this study. Chi-square test was used to test association between the type of caesarean section and demographic characteristics. Both binary and multivariate regression analysis were performed to assess the predictors of elective caesarean section at a p-value ≤ 0.05 and 95% confidence interval. Model fitness was rigorously conducted to ensure validity and reliability of study findings. The data was analysed using STATA version 14 SE.ResultsThe rate of CS among women who delivered (6,167) in the last five years preceding the survey was 1,015 (16.46%). Among the women who underwent CS, 36.6% opted for elective CS. Our findings showed that women aged 30 – 39 years were more likely to opt for elective CS [aOR: 3.130, 95%CI:1.969 - 4.978] compared to those aged 29 years or below. Women living in rural areas were less likely to opt for elective CS in the binary regression model [cOR: 0.587, 95%CI: 0.448 – 0.768]. Also, mothers who received ANC assistance by nurse/midwife were 40% less likely [aOR: 0.529, 95%CI: 0.349 – 0.803] to undergo elective CS, than those assisted by doctors.ConclusionThe rate of elective CS is very high among mothers in Rwanda. By using the 2019/20 RDHS data, the study found the key predictors behind the high rate of CS in Rwanda. These predictors should be deeply considered in developing comprehensive measures and policies to mitigate the unnecessary CS in Rwanda, which has detrimental impact on maternal and newborn outcome.
Single Cell Profiling Distinguishes Leukemia-Selective Chemotypes
Authors: Thirman Hannah L. , Hayes Madeline J. , Brown Lauren E. , Porco John A. , Irish Jonathan M. 
Published: May 2024

AbstractA central challenge in chemical biology is to distinguish molecular families in which small structural changes trigger large changes in cell biology. Such families might be ideal scaffolds for developing cell-selective chemical effectors – for example, molecules that activate DNA damage responses in malignant cells while sparing healthy cells. Across closely related structural variants, subtle structural changes have the potential to result in contrasting bioactivity patterns across different cell types. Here, we tested a 600-compound Diversity Set of screening molecules from the Boston University Center for Molecular Discovery (BU-CMD) in a novel phospho-flow assay that tracked fundamental cell biological processes, including DNA damage response, apoptosis, M-phase cell cycle, and protein synthesis in MV411 leukemia cells. Among the chemotypes screened, synthetic congeners of the rocaglate family were especially bioactive. In follow-up studies, 37 rocaglates were selected and deeply characterized using 12 million additional cellular measurements across MV411 leukemia cells and healthy peripheral blood mononuclear cells. Of the selected rocaglates, 92% displayed significant bioactivity in human cells, and 65% selectively induced DNA damage responses in leukemia and not healthy human blood cells. Furthermore, the signaling and cell-type selectivity were connected to structural features of rocaglate subfamilies. In particular, three rocaglates from the rocaglate pyrimidinone (RP) structural subclass were the only molecules that activated exceptional DNA damage responses in leukemia cells without activating a detectable DNA damage response in healthy cells. These results indicate that the RP subset should be extensively characterized for anticancer therapeutic potential as it relates to the DNA damage response. This single cell profiling approach advances a chemical biology platform to dissect how systematic variations in chemical structure can profoundly and differentially impact basic functions of healthy and diseased cells.
Uterus and cervix anatomical changes and cervix stiffness evolution throughout pregnancy
Authors: Louwagie Erin M. , Russell Serena R. , Hairston Jacqueline C. , Nottman Claire , Nhan-Chang Chia-Ling , Fuchs Karin , Gyamfi-Bannerman Cynthia , Booker Whitney , Andrikopoulou Maria , Friedman Alexander , Zork Noelia , Wapner Ronald , Vink Joy , Mourad Mirella , Feltovich Helen M. , House Michael D. , Myers Kristin M. 
Published: May 2024

AbstractThe coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.
Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts
Authors: Szadai Leticia , Bartha Aron , Parada Indira Pla , Lakatos Alexandra , Pál Dorottya , Lengyel Anna Sára , Almeida Natália Pinto de , Jánosi Ágnes Judit , Nogueira Fábio , Szeitz Beata , Doma Viktória , Woldmar Nicole , Guedes Jéssica , Ujfaludi Zsuzsanna , Pahi Zoltán Gábor , Pankotai Tibor , Kim Yonghyo , Győrffy Balázs , Baldetorp Bo , Welinder Charlotte , Szasz A. Marcell , Betancourt Lazaro , Gil Jeovanis , Appelqvist Roger , Kwon Ho-Jeong , Kárpáti Sarolta , Kuras Magdalena , Murillo Jimmy Rodriguez , Németh István Balázs , Malm Johan , Fenyö David , Pawłowski Krzysztof , Horvatovich Peter , Wieslander Elisabet , Kemény Lajos V. , Domont Gilberto , MarkoVarga György , Sanchez Aniel 
Published: May 2024

AbstractWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.Abstract Figure
Computational modelling of specific serotonin reuptake inhibitor inhibition on the TREK-2 channel
Authors: Pratueangsukpong Narawit , Pipatpolkai Tanadet 
Published: May 2024

AbstractThe TREK-2 is a mechanosensitive potassium channel in the two-pore (K2P) potassium channel subfamily. Recent studies of the TREK-2 channel with norfluoxetine reveal that norfluoxetine stabilises a conformation with a lower open probability and disrupts channel gating through a selectivity filter. In addition, multiple specific serotonin reuptake inhibitors (SSRIs) have previously been shown to inhibit the TREK channels subfamily. However, the mechanism of lipid-like SSRI inhibition to the TREK-2 channel is currently unclear. Using molecular dynamic simulation, we show that fluoxetine and escitalopram share the same binding pocket on the TREK-2 channel. We show that fluoxetine inhibits the TREK-2 channel using POPC lipid and directly disrupts the channel gating at the selectivity filter, while escitalopram is a traditional pore blocker, which also disrupts the selectivity filter gating but without POPC dependent inhibition. In addition, we show that both fluoxetine and escitalopram prevent a down-to-up transition when the pressure is applied to the system, showing a conserved mechanism of TREK-2 inhibition. Together, our work reveals mechanistic insight into TREK-2 channel inhibition by lipid-like antidepressants, which could further shed light on rational drug design in the future.
Tuning ice thickness using the chameleon for high-quality cryoEM data collection
Authors: McGuire Kelly L. , Cook Brian D. , Narehood Sarah M. , Herzik Mark A. 
Published: May 2024

AbstractAdvances in single-particle cryogenic electron microscopy (cryoEM) now allow for routine structure determination of well-behaved biological specimens to high-resolution. Despite advances in the electron microscope, direct electron detectors, and data processing software, the preparation of high-quality grids with thin layers of vitreous ice containing the specimen of interest in random orientations remains a critical bottleneck for many projects. Although numerous efforts have been dedicated to overcoming hurdles frequently encountered during specimen vitrification using traditional blot-and-plunge specimen preparation techniques, the development of blot-free grid preparation devices provide a unique opportunity to carefully tune ice thickness, particle density, and specimen behavior during the vitrification process for improvements in image quality. Here, we describe critical steps of high-quality grid preparation using a SPT Labtech chameleon, evaluation of grid quality/ice thickness using the chameleon software, high-throughput imaging in the electron microscope, and recommend steps for troubleshooting grid preparation when standard parameters fail to yield suitable specimen.Video LinkContents of this manuscript are available as a video tutorial. This video can be foundhere
PAM-free diagnostics with diverse type V CRISPR-Cas systems
Authors: Rananaware Santosh R. , Meister Katelyn S. , Shoemaker Grace M. , Vesco Emma K. , Sandoval Luke Samuel W. , Lewis Jordan G. , Bodin August P. , Karalkar Vedant N. , Lange Ian H. , Pizzano Brianna Lauren Maria , Chang Minji , Ahmadimashhadi M. Reza , Flannery Sarah J. , Nguyen Long. T. , Wang Gary P. , Jain Piyush K. 
Published: May 2024

AbstractType V CRISPR-Cas effectors have revolutionized molecular diagnostics by facilitating the detection of nucleic acid biomarkers. However, their dependence on the presence of protospacer adjacent motif (PAM) sites on the target double-stranded DNA (dsDNA) greatly limits their flexibility as diagnostic tools. Here we present a novel method named PICNIC that solves the PAM problem for CRISPR-based diagnostics with just a simple ∼10-min modification to contemporary CRISPR-detection protocols. Our method involves the separation of dsDNA into individual single-stranded DNA (ssDNA) strands through a high- temperature and high-pH treatment. We then detect the released ssDNA strands with diverse Cas12 enzymes in a PAM-free manner. We show the utility of PICNIC by successfully applying it for PAM-free detection with three different subtypes of the Cas12 family- Cas12a, Cas12b, and Cas12i. Notably, by combining PICNIC with a truncated 15-nucleotide spacer containing crRNA, we demonstrate PAM-independent detection of clinically important single- nucleotide polymorphisms with CRISPR. We apply this approach to detect the presence of a drug-resistant variant of HIV-1, specifically the K103N mutant, that lacks a PAM site in the vicinity of the mutation. Additionally, we successfully translate our approach to clinical samples by detecting and genotyping HCV-1a and HCV-1b variants with 100% specificity at a PAM-less site within the HCV genome. In summary, PICNIC is a simple yet groundbreaking method that enhances the flexibility and precision of CRISPR-Cas12-based diagnostics by eliminating the restriction of the PAM sequence.