bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRO‐seq: Precise Mapping of Engaged RNA Pol II at Single‐Nucleotide Resolution
Authors: Mimoso Claudia A. , Goldman Seth R. 
Published: December 2023

AbstractGene regulation is dependent on the production of mRNAs and a repertoire of non‐coding RNAs by RNA polymerase II (RNAPII). Precision run‐on sequencing (PRO‐seq) maps the position of engaged RNAPII complexes at single‐nucleotide resolution and can reveal direct targets of regulation, locations of enhancers, and transcription mechanisms that are difficult or impossible to measure by analysis of total cellular RNA. Briefly, this method first involves permeabilizing cells with mild detergents to remove intracellular NTPs and halt transcription. Transcription is then resumed in the presence of biotin‐NTPs and sarkosyl to allow transcriptional incorporation of a single biotinylated NTP by RNAPII. The biotin moiety is then bound to streptavidin beads to stringently enrich for nascent RNAs. Sequencing libraries are then generated such that the first base read corresponds to the 3′ end of the nascent transcript. Here, we describe our current protocol for generating PRO‐seq libraries from metazoan cells, including adaptations of previously published protocols to incorporate unique molecular identifiers, reduce ligation bias, and improve library yields. Additional commentary describes quality control and processing of PRO‐seq data and references for more advanced downstream analysis such as gene and enhancer identification. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Cell permeabilization for PRO‐seqBasic Protocol 2: Construction of PRO‐seq librariesSupport Protocol: Adenylation of 3′ adapter
Top Alzheimer's disease risk allele frequencies differ in HABS‐HD Mexican‐ versus Non‐Hispanic White Americans
Authors: Housini Mohammad , Zhou Zhengyang , Gutierrez John , Rao Sumedha , Jomaa Rodwan , Subasinghe Kumudu , Reid Danielle Marie , Silzer Talisa , Phillips Nicole , O'Bryant Sid , Barber Robert Clinton ,   For the HABS‐HD Study Team
Published: December 2023

AbstractINTRODUCTION: Here we evaluate frequencies of the top 10 Alzheimer's disease (AD) risk alleles for late‐onset AD in Mexican American (MA) and non‐Hispanic White (NHW) American participants enrolled in the Health and Aging Brain Study–Health Disparities Study cohort.METHODS: Using DNA extracted from this community‐based diverse population, we calculated the genotype frequencies in each population to determine whether a significant difference is detected between the different ethnicities. DNA genotyping was performed per manufacturers’ protocols.RESULTS: Allele and genotype frequencies for 9 of the 11 single nucleotide polymorphisms (two apolipoprotein E variants, CR1, BIN1, DRB1, NYAP1, PTK2B, FERMT2, and ABCA7) differed significantly between MAs and NHWs.DISCUSSION: The significant differences in frequencies of top AD risk alleles observed here across MAs and NHWs suggest that ethnicity‐specific genetic risks for AD exist. Given our results, we are advancing additional projects to further elucidate ethnicity‐specific differences in AD.
Identification of antibiotic‐resistant pathogens and virulence genes in Escherichia coli isolates from food samples in the Dhaka University campus of Bangladesh
Authors: Bakshi Progati , Bhowmik Anindita , Ahsan Sunjukta , Alim Sharmin Rumi 
Published: December 2023

AbstractThe presence of antibiotic‐resistant pathogens in food is a serious public health concern nowadays. This study focuses on the isolation and characterization of potentially pathogenic Escherichia coli and antimicrobial‐resistant pathogens in chicken curry and potato smash samples collected from the canteens and cafeteria of Dhaka University in Bangladesh. Isolates were identified by their cultural, morphological, and biochemical tests (motility indole urease test, Kliger's iron agar test, catalase test, oxidase test, methyl red and Voges‐Proskauer tests). The antibiotic susceptibility test was done by the disk diffusion method. The range of total bacterial count in the potato smash and chicken curry samples was from 1.4 × 104 to 1.6 × 108 CFU/g and from 2.4 × 103 to 2.6 × 106 CFU/g, respectively. Escherichia coli, Salmonella, Vibrio, Klebsiella, Citrobacter, Enterobacter, Proteus, Clostridium, Staphylococcus, Streptococcus, Micrococcus, Bacillus, and Sarcina strains were isolated in both samples. Isolates were highly resistant to ampicillin (90.90%) followed by colistin (52.27%), azithromycin (27.27%), and tetracycline 25%. Proteus species had the highest rate of multiple antibiotic resistance (MAR; 62.5%), followed by Citrobacter species (50%). The isolated E. coli strains were further analyzed through PCR assay to detect virulent genes (EPEC: eaeA 229 bp, bfpA 450 bp, ETEC elt 322 bp, EHEC hylA 534 bp, and EIEC ial 320 bp). One E. coli isolate had the eaeA target gene under EPEC pathotypes. Escherichia coli, as a fecal indicator, may indicate fecal contamination or poor and unhygienic food handling. The findings recommend further investigations to identify potential mechanisms of contamination and preventive measures to improve the food safety level in the canteens and restaurants.
Evaluation of techniques to break seed dormancy in Redroot pigweed (Amaranthus retroflexus)
Authors: Ahmadnia Fatemeh , Alebrahim Mohammad Taghi , Nabati Souha Leyli , MacGregor Dana R. 
Published: December 2023

AbstractBy identifying the factors that initiate seed dormancy release, we can reliably predict whether a seed will remain dormant within or exit the seed bank and become a seedling. With regard to annual weed species, assessing which factors efficiently break seed dormancy is critical for estimating the number of weed seeds that will develop into problematic weeds. To better understand dormancy breaking in Redroot pigweed (Amaranthus retroflexus), dormant seeds were treated with cold stratification (4°C for 30 days), application of gibberellic acid (at 500, 1000, 1500, and 2000 parts per million), ultrasound (for 10, 20, 30, and 40 min), soaking in hot water (90°C for 3, 5, 7, and 10 min), and 98% sulfuric acid (for 1, 2, and 3 min). The results showed that Redroot pigweed seed dormancy was effectively broken by cold stratification, gibberellic acid, and ultrasound. Short treatments with hot water had minimal effect while longer times or treatment with sulfuric acid stopped seed germination. In addition to germination percentage, germination rate, plumule length, radicle length, seedling length, seedling dry weight, and seed vigor index were also measured; similarly, application of gibberellic acid had the most significant effect on these parameters. The results of this study add to our knowledge of what processes effectively or ineffectively break Redroot pigweed seed dormancy and promote growth.
How important are delays in treatment for health outcomes? The case of ambulance response time and cardiovascular events
Authors: Lucchese Elena 
Published: December 2023

AbstractThe cost effectiveness of medical treatments is not precisely known due to the compounding effect of multiple determining factors. Ambulance response time (RT) to emergency calls is exploited to learn more about the effect of the timing of treatment on health outcomes. This causal relation is identified by exploiting rainfall at the time of the ambulance run as a shock to RT. The analysis focuses on patients who have undergone a cardiac event and shows that a one‐minute increase in average RT leads to 105 more deaths each year in one Italian region. Finally, the economic value of the lives that would be saved by reducing RT is quantified to facilitate policymaking.
Habit and persistence
Authors: Bouton Mark E. 
Published: December 2023

AbstractVoluntary behaviors (operants) can come in two varieties: Goal‐directed actions, which are emitted based on the remembered value of the reinforcer, and habits, which are evoked by antecedent cues and performed without the reinforcer's value in active memory. The two are perhaps most clearly distinguished with the reinforcer‐devaluation test: Goal‐directed actions are suppressed when the reinforcer is separately devalued and responding is tested in extinction, and habitual behaviors are not. But what is the function of habit learning? Habits are often thought to be strong and unusually persistent. The present selective review examines this idea by asking whether habits identified by the reinforcer‐devaluation test are more resistant to extinction, resistant to the effects of other contingency change, vulnerable to relapse, resistant to the weakening effects of context change, or permanently in place once they are learned. Surprisingly little evidence supports the idea that habits are permanent or more persistent. Habits are more context‐specific than goal‐directed actions are. Methods that make behavior persistent do not necessarily work by encouraging habit. The function of habit learning may not be to make a behavior strong or more persistent but to make it automatic and efficient in a particular context.
Does stress make males? An experiment on the role of glucocorticoids in anuran sex reversal
Authors: Bókony Veronika , Kalina Csenge , Ujhegyi Nikolett , Mikó Zsanett , Lefler Kinga Katalin , Vili Nóra , Gál Zoltán , Gabor Caitlin R. , Hoffmann Orsolya Ivett 
Published: December 2023

AbstractEnvironmentally sensitive sex determination may help organisms adapt to environmental change but also makes them vulnerable to anthropogenic stressors, with diverse consequences for population dynamics and evolution. The mechanisms translating environmental stimuli to sex are controversial: although several fish experiments supported the mediator role of glucocorticoid hormones, results on some reptiles challenged it. We tested this hypothesis in amphibians by investigating the effect of corticosterone on sex determination in agile frogs (Rana dalmatina). This species is liable to environmental sex reversal whereby genetic females develop into phenotypic males. After exposing tadpoles during sex determination to waterborne corticosterone, the proportion of genetic females with testes or ovotestes increased from 11% to up to 32% at 3 out of 4 concentrations. These differences were not statistically significant except for the group treated with 10 nM corticosterone, and there was no monotonous dose‐effect relationship. These findings suggest that corticosterone is unlikely to mediate sex reversal in frogs. Unexpectedly, animals originating from urban habitats had higher sex‐reversal and corticosterone‐release rates, reduced body mass and development speed, and lower survival compared to individuals collected from woodland habitats. Thus, anthropogenic environments may affect both sex and fitness, and the underlying mechanisms may vary across ectothermic vertebrates.
Design, enantioselective synthesis, and antiviral activities against potato virus Y of axially chiral thiazine derivatives
Authors: Shen Tingwei , Jin Jiamiao , Song Jia , Naz Hira , Jin Zhichao , Chi Yonggui Robin , Wu Xingxing 
Published: December 2023

AbstractA series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N‐heterocyclic carbene (NHC)‐catalyzed enantioselective [3 + 3] annulations, and their potential as anti‐plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S)‐3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S)‐3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S)‐3g against PVY, wherein single enantiomer (S)‐3g formed a more stable interaction with PVY‐CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)‐3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.
Deep‐Learning‐Based MRI Microbleeds Detection for Cerebral Small Vessel Disease on Quantitative Susceptibility Mapping
Authors: Xia Peng , Hui Edward S. , Chua Bryan J. , Huang Fan , Wang Zuojun , Zhang Huiqin , Yu Han , Lau Kui Kai , Mak Henry K.F. , Cao Peng 
Published: December 2023

BackgroundCerebral microbleeds (CMB) are indicators of severe cerebral small vessel disease (CSVD) that can be identified through hemosiderin‐sensitive sequences in MRI. Specifically, quantitative susceptibility mapping (QSM) and deep learning were applied to detect CMBs in MRI.PurposeTo automatically detect CMB on QSM, we proposed a two‐stage deep learning pipeline.Study TypeRetrospective.SubjectsA total number of 1843 CMBs from 393 patients (69 ± 12) with cerebral small vessel disease were included in this study. Seventy‐eight subjects (70 ± 13) were used as external testing.Field Strength/Sequence3 T/QSM.AssessmentThe proposed pipeline consisted of two stages. In stage I, 2.5D fast radial symmetry transform (FRST) algorithm along with a one‐layer convolutional network was used to identify CMB candidate regions in QSM images. In stage II, the V‐Net was utilized to reduce false positives. The V‐Net was trained using CMB and non CMB labels, which allowed for high‐level feature extraction and differentiation between CMBs and CMB mimics like vessels. The location of CMB was assessed according to the microbleeds anatomical rating scale (MARS) system.Statistical TestsThe sensitivity and positive predicative value (PPV) were reported to evaluate the performance of the model. The number of false positive per subject was presented.ResultsOur pipeline demonstrated high sensitivities of up to 94.9% at stage I and 93.5% at stage II. The overall sensitivity was 88.9%, and the false positive rate per subject was 2.87. With respect to MARS, sensitivities of above 85% were observed for nine different brain regions.Data ConclusionWe have presented a deep learning pipeline for detecting CMB in the CSVD cohort, along with a semi‐automated MARS scoring system using the proposed method. Our results demonstrated the successful application of deep learning for CMB detection on QSM and outperformed previous handcrafted methods.Level of Evidence2Technical EfficacyStage 2
Comparing single versus multiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT‐PCR diagnostic testing
Authors: Hazan Guy , Goldstein Yoav , Greenberg David , Khalde Firas , Mahajna Rofaida , Keren‐Naos Ayelet , Hershkovitz Eli , Faingelernt Yaniv , Givon‐Lavi Noga , Danino Dana 
Published: December 2023

AbstractUtilizing multiplex real time polymerase chain reaction (RT‐PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter‐spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co‐infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.
Increased diurnal temperature range in global drylands in more recent decades
Authors: Daramola Mojolaoluwa T. , Li Renqiang , Xu Ming 
Published: December 2023

AbstractThe diurnal temperature range (DTR) has generally decreased at global scale according to the IPCC reports and previous publications. Here, we examined the change in DTR within the past four decades and found that DTR decreased in wet areas, but it increased in dry areas. This is because the daily minimum air temperature (Tmin) increased at a slower rate than the daily maximum air temperature (Tmax) in the dry areas, while it increased more rapidly in the wet areas. The changes in cloud cover, water vapour and moisture flux were observed to have contributed to the observed change in DTR. The change in moisture flux largely contributed to this change through the indirect effect on the change in water vapour across the aridity gradient. The significant impact of moisture flux is linked to the differential change in moisture flux between the dry and wet zones.
Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil‐derived neurotoxin
Authors: Thomas Jessina , Hopson Puanani , Deb Chirajyoti , Bornstein Jeffrey , Mehta Devendra , Bittar Khaled , Smadi Yamen 
Published: December 2023

AbstractObjectivesEosinophil‐derived neurotoxin (EDN) is a viable marker of eosinophilic esophagitis (EoE) disease activity. We studied the utility of measuring EDN from esophageal epithelial brushings for diagnosing EoE, focusing on two scenarios: (1) cases of exclusive distal eosinophilia and (2) cases of discrepancy between endoscopy and histology.MethodsRecords of patients who underwent esophagogastroduodenoscopy (EGD) with EDN measured via esophageal brushings at Arnold Palmer Hospital for Children in Orlando, Florida from January 2014 to October 2018 were retrospectively reviewed. Demographics, clinical, endoscopic, and histologic data were collected.ResultsWe reviewed 231 patient records (66.7% male, mean age 10.3 years, range 1–22 years). EDN values correlated with endoscopic reference score (EREFS) and peak eosinophil count (PEC) (Spearman's rho = 0.756 (p < 0.001) and 0.824 (p < 0.001) respectively). Average PEC, EREFS, and EDN concentrations were higher in patients with active EoE than in controls or patients with EoE in remission (inactive). When grouping patients based on esophageal eosinophilia distribution, EDN mirrored PEC, and EREFS. Patients with exclusive distal eosinophilia had lower EDN concentrations than those with eosinophilia in >1 level of the esophagus (23.8 ± 46.1 mcg/mL vs. 171.3 ± 205.8 mcg/mL respectively, p < 0.001). EDN values were more consistent with EREFS in cases of discrepancies between endoscopic findings and pathology (p < 0.001).ConclusionEDN measured in esophageal brushing samples reflects disease activity objectively and accurately. It also offers significant value in cases of exclusive distal esophageal eosinophilia and when discrepancies exist between endoscopy and histology.
Anti‐infliximab antibodies and low infliximab levels correlate with drug discontinuation in pediatric inflammatory bowel disease
Authors: Zitomersky Naamah , Chi Lisa , Liu Enju , Bray Kurtis R. , Papamichael Konstantinos , Cheifetz Adam S. , Snapper Scott B. , Bousvaros Athos , Silvester Jocelyn A. 
Published: December 2023

AbstractBackgroundInfliximab (IFX) use is limited by loss of response often due to the development of anti‐IFX antibodies and low drug levels.MethodsWe performed a single center prospective observational cohort study of pediatric and young adult subjects with inflammatory bowel disease (IBD) on IFX with over 3 years of follow‐up. Infliximab levels (IFXL) and antibodies to infliximab (ATI) were measured throughout the study. Subjects were followed until IFX was discontinued.ResultsWe enrolled 219 subjects with IBD (184: Crohn's disease; 33: Ulcerative colitis; and 2 Indeterminant colitis; 84 female, median age 14.4 years, 37% on concomitant immunomodulator). Nine hundred and nineteen serum samples (mean 4.2 ± 2.1 per patient) were tested for IFXL and ATI. During the study, 31 (14%) subjects discontinued IFX. Sixty patients had ATI. Twenty‐two of those 60 patients with ATI discontinued IFX; 14 of 31 patients who discontinued IFX had detectable ATI at study onset. The combination of ATI and IFXL < 5 µg/mL at study entry was associated with the highest risk of drug discontinuation (hazard ratios [HR] ATI 4.27 [p < 0.001] and IFXL < 5 µg/mL [HR]: 3.2 p = 0.001). Patients with IFXL 5–10 µg/mL had the lowest rate of discontinuation (6%). IFX dose escalation eliminated ATI in 21 of 60 subjects.ConclusionsATI is a strong predictor of needing to stop IFX use and inversely correlates with IFXL. Detection of ATI during therapeutic drug monitoring postinduction but also periodically during maintenance therapy identifies individuals who may benefit from IFX dose escalation and/or the addition of an immunomodulator, as these interventions may reduce or eliminate ATI.
Management patterns of multiple magnet ingestion reported to New Jersey Poison Information and Education System
Authors: Nguyen Tuyet‐Anh T. , Calello Diane P. , Ruck Bruce , Loughran David E. , Greller Howard A. , Meaden Christopher W. 
Published: December 2023

AbstractBackgroundIngestion of multiple high‐powered neodymium rare‐earth magnets poses a significant risk for gastrointestinal (GI) injury such as bowel perforation or ischemia. Given the rising incidence of rare earth magnetic ingestions and the corresponding increase in serious injuries in children, published guidelines recommend urgent endoscopic removal of all magnets within endoscopic reach in cases involving ingestions of two or more magnets.Research QuestionDo management patterns for multiple magnet ingestion align with current practice guidelines, and does hospital length of stay (LOS) differ based on the initial emergency department (ED) approach?MethodsThis is a retrospective chart review of consecutive patient encounters reported to the New Jersey Poison Information and Education System (NJPIES) between January 2021 and April 2022 involving multiple magnet ingestion. Potential cases were retrieved from the NJPIES TOXICALL® database, using substance codes relating to magnet or foreign body ingestion. Two‐sample T tests were used to determine the statistical difference in the hospital LOS between the group of patients receiving early emergent esophagogastroduodenoscopy (EGD) versus those receiving expectant management on initial presentation.ResultsThere was a difference in the average LOS of 2.7 days (p = 0.023) longer in the expectant management group with no medical complications in either group. Twenty‐five percent or 2 out of 8 cases deviated from guidelines.ConclusionThe initial ED decision to pursue expectant management instead of attempting emergent EGD removal of magnets may result in prolonged hospitalization, increased risk for readmission, and delayed definitive removal of magnets due to nonprogression along the GI tract.
Symptomatic hypercalcemia in an infant secondary to excessive consumption of almond milk as a formula alternative
Authors: Gulledge Whitney C. , Gerald Brittany M. , Sumpter Kathryn M. , Rogers Nathaniel G. 
Published: December 2023

AbstractA 4‐month‐old previously healthy female presented with persistent nonbloody, nonbilious emesis, decreased urine output, weight loss, fussiness, and lethargy. Serum levels of calcium were increased at 14.1 mg/dL, serum phosphate decreased at 1.6 mg/dL, and serum parathyroid hormone decreased at <4 pg/mL. The patient had been consuming unsweetened almond milk due to inability to find infant formula during a national infant formula shortage. Milk alternatives including almond milk are calorie‐poor, low fat, low protein, and too high in free water and calcium to safely be the primary nutrition source for infants.