bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder
Authors: Argonis Riley A. , Pedapati Ernest V. , Dominick Kelli C. , Harris Katherine , Lamy Martine , Fosdick Cara , Schmitt Lauren , Shaffer Rebecca C. , Smith Elizabeth , Will Meredith , McDougle Christopher J. , Erickson Craig A. 
Published: October 2022

AbstractDepression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 170 individuals with ASD (mean age 16.2±8.7 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 247 drug starts, 121 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ±0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.
Analysis of Adverse Drug Events of Opioids in the United States
Authors: Liu Edward Y. , McCall Kenneth L. , Piper Brian J. 
Published: October 2022

AbstractThe United States (US) is going through an opioid crisis with annual increases in opioid-related mortality. Our study analyzed the adverse drugs events (ADEs) for eleven prescription opioids when correcting for distribution, and their ratios for three periods: 2006-2010, 2011-2016, and 2017-2021 in the US. The opioids included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. The Food and Drug Administration Adverse Event Reporting System (FAERS) database consists of reports by MedWatch adverse event forms submitted by healthcare professionals and others (N=667,969), whereas the Automation of Reports and Consolidated Orders System (ARCOS) reports on medically used controlled substances. Oral morphine milligram equivalents (MMEs) were calculated by conversion relative to morphine. The relative ADEs of the select opioids calculated from FAERs, opioid distribution from ARCOS, and the FAERs to ARCOS ratios were analyzed for the eleven opioids. Oxycodone reports peaked in the third period and showed consistently high ADEs. Codeine and meperidine accounted less than five percent of ADEs. The ARCOS distributions were relatively constant over time, but methadone consistently accounted for the largest portion of the total distribution. The FAERS to ARCOS ratios generally increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol 10.3, and hydromorphone (7.9) most over-represented for ADEs in the third period. Oxymorphone had a 542.2% increase in ratio between the second and third period should be noted. Methadone was under-represented (< .20) in all three periods. These findings indicate the need to further monitor and address the ADEs of select opioids.SignificancePrescription opioid use in the US is among the highest in the world. This study analyzed both FAERs and ARCOS databases to understand the adverse drugs events. This investigation identified which opioids were overrepresented (e.g. meperidine) and underrepresented (e.g. methadone) for adverse effects relative to the prevalence of use to inform healthcare policies and change the way physicians view and prescribe these opioids.
Genome-wide Analysis of Rare Haplotypes Associated with Breast Cancer Risk: Discovery, Replication, and Generalizability Evaluation
Authors: Wang Fan , Moon Wonjong , Letsou William , Sapkota Yadav , Wang Zhaoming , Im Cindy , Baedke Jessica L. , Robison Leslie , Yasui Yutaka 
Published: October 2022

AbstractWhile numerous common variants have been linked to breast cancer (BCa) risk, they explain only partially the total BCa heritability. Inference from the Nordic population-based twin data indicates that rare high-risk loci are the chief determinant of BCa risk. Here, we use haplotypes, rather than single variants, to identify rare high-risk loci for BCa. With computationally phased genotypes from 181,034 white British women in the UK Biobank, we conducted a genome-wide haplotype-BCa association analysis using sliding windows of 5-500 consecutive array-genotyped variants. In the discovery stage, haplotype associations with BCa risk were evaluated retrospectively in the pre-study-enrollment portion of data including 5,487 BCa cases. BCa hazard ratios (HRs) for additive haplotypic effects were estimated using Cox regression. Our replication analysis included women free of BCa at enrollment, of whom 3,524 later developed BCa. This two-stage analysis detected 13 rare loci (frequency <1%), each associated with an appreciable BCa risk increase (discovery: HRs=2.84-6.10, P-value<5×10−8; replication: HRs=2.08-5.61, P-value<0.01). In contrast, the variants that formed these rare haplotypes individually exhibited much smaller effects. Functional annotation revealed extensive cis-regulatory DNA elements in BCa-related cells underlying the replicated rare haplotypes. Using phased, imputed genotypes from 30,064 cases and 25,282 controls in the DRIVE OncoArray case-control study, six of the 13 rare-loci associations proved generalizability (odds ratio estimates: 1.48-7.67, P-value<0.05). This study demonstrates the complementary advantage of utilizing rare haplotypes to capture novel risk loci and possible discoveries of more genetic elements contributing to BCa heritability once large, germline whole-genome sequencing data become available.
Impact of the COVID-19 pandemic on the circulation of other pathogens in England
Authors: Hayes Lauren , Uri Hannah , Bojkova Denisa , Cinatl Jindrich , Wass Mark N. , Michaelis Martin 
Published: October 2022

AbstractThe COVID-19 pandemic and the associated prevention measures did not only impact on the transmission of COVID-19 but also on the spread of other infectious diseases in an unprecedented natural experiment. Here, we analysed the transmission patterns of 22 different infectious diseases during the COVID-19 pandemic in England. Our results show that the COVID-19 prevention measures generally reduced the spread of pathogens that are transmitted via the air and the faecal-oral route. Moreover, the COVID-19 prevention measures resulted in the sustained suppression of vaccine-preventable infectious diseases also after the removal of restrictions, while non-vaccine preventable diseases displayed a rapid rebound. Despite concerns that a lack of exposure to common pathogens may affect population immunity and result in large outbreaks by various pathogens post-COVID-19, only four of the 22 investigated diseases and disease groups displayed higher post-than pre-pandemic levels without an obvious causative relationship. Notably, this included chickenpox for which an effective vaccine is available but not used in the UK, which provides strong evidence supporting the inclusion of the chickenpox vaccination into the routine vaccination schedule in the UK. In conclusion, our findings provide unique, novel insights into the impact of non-pharmaceutical interventions on the spread of a broad range of infectious diseases.
Online survey of treatment experiences for obsessive-compulsive disorder
Authors: Kirkham E.J. , Cao Y. , Król M. 
Published: October 2022

AbstractIntroductionThere is a lack of knowledge about the treatment experiences of people living with obsessive-compulsive disorder (OCD).MethodParticipants with OCD (n= 202) took part in an online survey in which they answered questions about what treatment they had received. They also completed measures of current OCD, anxiety and depression.ResultsScores above the clinical cut-off for OCD were high (> 70%) across the sample, irrespective of what kind of treatment had been received. Despite this, most participants felt their OCD was better now than it had been pre-treatment. Mean OCD scores were similar between treatment groups (OCD-focused, partly OCD-focused, non-OCD focused, no treatment), though there was some evidence that OCD-focused treatment was associated with lower OCD scores, especially for symptoms of hoarding, neutralising and ordering.DiscussionThese findings contribute to evidence of unmet need in OCD care. Practitioners should be aware that OCD is often a chronic condition which requires specialist care, and may require more than one course of treatment.
Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors
Authors: Chen Yu , Yamamoto Tatsuki , Takahashi Yura , Moro Tomoka , Tajima Tomoko , Sakaguchi Yukiko , Sakata Naoaki , Yokoyama Akihiko , Hijioka Susumu , Sada Akane , Tabata Yuko , Ohki Rieko 
Published: October 2022

ABSTRACTInsulin signaling often plays a role in the regulation of cancer including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We therefore investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signal within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.
Possible adaption of the 2022 Monkeypox virus to the human host through gene duplication and loss
Authors: Brinkmann Annika , Kohl Claudia , Pape Katharina , Bourquain Daniel , Thürmer Andrea , Michel Janine , Schaade Lars , Nitsche Andreas 
Published: October 2022

AbstractPoxviruses are known to evolve slower than RNA viruses, with rearrangements such as gene gain and loss as the main driver for host adaption. In 2022 the world is being challenged by the largest global outbreak so far of Monkeypox virus, and the virus seems to have established itself in the human community. Here we report five MPXV genomes with extensive gene duplication and loss, including duplications of up to 18,000 bp to the opposed genome end, and deletions at the site of insertion of up to 16,000 bp, as a possible adaption to the human host.
Taste receptor T1R3 in nasal cilia detectsStaphylococcus aureusD-amino acids to increase apical glucose uptake and enhance innate immunity
Authors: Carey Ryan M. , Hariri Benjamin M. , Adappa Nithin D. , Palmer James N. , Margolskee Robert F. , Cohen Noam A. , Lee Robert J. 
Published: October 2022

SUMMARYBitter (T2R) and sweet/umami (T1R) taste receptors serve chemosensory roles throughout the body. In airway cilia, T2Rs detect bacterial metabolites to stimulate bactericidal nitric oxide. T1Rs in solitary chemosensory cells detect glucose in airway surface liquid (ASL) and bacterial D-stereoisomer amino acids to regulate antimicrobial peptides. Using differentiated air-liquid interface cultures of primary nasal cells, we show that the T1R3 receptor is also expressed in human and mouse nasal cell cilia. D-amino acids produced at low mM concentrations byStaphylococcus aureusactivate T1R3 to decrease ASL glucose and increase apical glucose uptake by increasing GLUT2 and GLUT10 expression through a β-arrestin pathway. Our data suggests that T1R3 localized to cilia functions as an immune detector for D-amino acids to reduce ASL glucose and potentially limit bacterial growth. Given that glucose protectedS. aureusagainst bactericidal NO produced during T2R activation, the reduced ASL glucose with T1R3 activation may also sensitize bacteria to other innate defenses.HIGHLIGHTSNasal motile cilia express the T1R3 subunit of the sweet taste receptorS. aureusD-amino acids activate cilia T1R3 to enhance mucosal glucose uptakeReduced airway surface liquid glucose likely reducesS. aureusgrowthReduced airway glucose also sensitizesS. aureusto epithelial NO production
Optical mapping of ground reaction force dynamics in freely behavingDrosophila melanogasterlarvae
Authors: Booth Jonathan H. , Meek Andrew T. , Kronenberg Nils M. , Pulver Stefan R. , Gather Malte C. 
Published: October 2022

AbstractDuring locomotion, soft-bodied terrestrial animals solve complex control problems at substrate interfaces, but our understanding of how they achieve this without rigid components remains incomplete. Here, we develop new all-optical methods based on optical interference in a deformable substrate to measure ground reaction forces (GRFs) with micrometre and nanonewton precision in behavingDrosophilalarvae. Combining this with a kinematic analysis of substrate interfacing features, we shed new light onto the biomechanical control of larval locomotion. Crawling in larvae measuring ∼1 mm in length involves an intricate pattern of cuticle sequestration and planting, producing GRFs of 1-7 µN. We show that larvae insert and expand denticulated, feet-like structures into substrates as they move, a process not previously observed in soft bodied animals. These ‘protopodia’ form dynamic anchors to compensate counteracting forces. Our work provides a framework for future biomechanics research in soft-bodied animals and promises to inspire improved soft-robot design.
Development of a High-Throughput Minimum Inhibitory Concentration (HT-MIC) Testing Workflow
Authors: Tiwari Suman , Nizet Oliver , Dillon Nicholas 
Published: October 2022

AbstractThe roots of the minimum inhibitory concentration (MIC) determination go back to the early 1900s. Since then, the test has undergone modifications and advancements in an effort to increase its dependability and accuracy. Although biological investigations use an ever-increasing number of samples, complicated processes and human error sometimes result in poor data quality, which makes it challenging to replicate scientific conclusions. The automation of the few manual steps using protocols decipherable by machine can ease some of the procedural difficulties. Originally relying on manual pipetting and human vision to determine the results, modern broth dilution MIC testing procedures have incorporated microplate readers to enhance sample analysis. However, current MIC testing procedures are unable to simultaneously evaluate a large number of samples efficiently. Here, we have created a workflow using the Opentrons OT-2 robot to enable high-throughput MIC testing. We have further optimized the analysis by incorporating Python programming for MIC assignment to streamline the automation. In this workflow, we performed MIC tests on four different strains, three replicates per strain, and analyzed a total of 1,152 wells. Comparing our our workflow to a conventional plate MIC procedure, we find that the HT-MIC method is 630% faster while simulataneously boasting a 100% accuracy. Our high-throughput MIC workflow can be applied in both academic and clinical settings since it is faster, more efficient, and more accurate than many conventional methods.
Identifying fungal leaf spots on oilseed rape: could pictures help?
Authors: Bousset L. , Ermel M. , Bammé B. , Penaud A. , Carpezat J. , Balesdent MH. , Laval V. , Palerme M. , Parisey N. 
Published: October 2022

AbstractFrom sowing in late summer until harvest in following summer, oilseed rape can be infected by several fungi, which foliar symptoms (leaf spots) coexist on the crop. Training an expert at their identification is quick for the typical symptoms with characteristic appearance. However, in many cases the size, colour and morphology are similar and for the atypical symptoms, there is a risk of confusion or in-decidability. Also, scouting the fields for expert training is not possible at all seasons and all diseases might not be seen in all years and all places. The aim of our study was to produce large sets of pictures annotated by several experts, from which tables illustrating the diversity of symptom appearance were chosen. These tables will enable assistance to diagnostic and expert training.
Highly structured habitats mitigate size- and growth-selective mortality of post-settlement juvenile fish
Authors: Kamimura Yasuhiro , Shoji Jun 
Published: October 2022

AbstractThe role of vegetated habitats such as seagrass and macroalgal beds as nurseries is essential for the survival of larval and juvenile fish, although quantitative evaluation of the contribution of these habitats to nursery function is limited. Moreover, growth–survival relationships of larvae and juveniles associated with vegetated habitats have rarely been examined. To quantitatively and qualitatively evaluate the processes affecting juvenile survival in vegetated habitats, we investigated whether there is a correlation between the degree of selection for bigger and faster-growing fish and mortality rates for three cohorts by birth date of post-settlement black rockfish (Sebastes cheni) in a macroalgal bed. We also analyzed relationships between growth rate and experienced temperature by age class to examine the effects of temperature on growth. The latest cohort, which grew under lower vegetation coverage due to a seasonal increase in water temperature, showed higher mortality with evidence of strong selection for bigger and faster-growing fish. The growth–temperature relationships showed that positive effects of temperature on growth weakened after settlement. Therefore, we suggest that macroalgal coverage has a critical role controlling the growth–mortality relationship of post-settlementS. cheni. Furthermore, the negative effects of high temperature on juvenile survival through loss of vegetation may be greater than the positive effects on juvenile growth. These findings will contribute to the management of fisheries resources by increasing the understanding of relationships between survival mechanisms in fish early life stages and vegetation phenology of their habitat under the increasing effects of global warming.
Two closed conformations of CRAF require the 14-3-3 binding motifs and cysteine-rich domain to be intact in live cells
Authors: Okamoto Kenji , Sako Yasushi 
Published: October 2022

AbstractThe protein rapidly accelerated fibrosarcoma (RAF) is a kinase downstream of the membrane protein RAS in the cellular signal transduction system. In the structure of RAF, the N- and C-terminus domains are connected with a flexible linker. The open/close dynamics and dimerization of RAF are thought to regulate its activity, although the details of these conformations are unknown, especially in live cells. In this work, we used alternating laser excitation to measure cytosolic CRAF in live HeLa cells and obtained single-molecule Förster resonance energy transfer (smFRET) distributions of the structural states. We compared the results for wild-type (WT)-CRAF before and after epidermal growth factor (EGF) stimulation, with mutations of the 14-3-3 binding sites and cysteine-rich domain, and an N-terminus truncation. The smFRET distributions of full-length CRAFs were analyzed by global fitting with three beta distributions. Our results suggested that a 14-3-3 dimer bound to two sites on a single CRAF molecule and induced the formation of the autoinhibitory closed conformation. There were two closed conformations, which the majority of WT-CRAF adopted. These two conformations showed different responsiveness to EGF stimulation.
PAM-less Exonuclease-assisted Cas12a for visual detection of Vibrio Species
Authors: Zhang Derek Han , Raykar Siddharth , Ng Kenneth Tsz Chun 
Published: October 2022

AbstractFoodborne pathogens, includingVibrio spp. and norovirus, cause substantial economic and healthcare burdens worldwide. Rapid and sensitive point-of-care testing on-farm or restaurants for batch inspection of pathogenic contamination in raw food products is essential. Here, we present an easy-to-design, cost-effective PAM-less Exonuclease-assisted Cas12A Nucleic-acid Detection (PECAN) assay paired with nucleic acid amplification systems for rapid and sensitive visual detection of 2 pathogenic Vibrio species:Vibrio parahaemolyticus(TDH) andVibrio Cholerae(ctxA) without protospacer adjacent motif (PAM) site limitation. With T7 exonuclease, PAM-less detection could be achieved with a low concentration of cas12a, costing $0.8 USD per reaction. The system could also be adapted for PAM-less cas12a nucleic acid detection in-field or in-lab for sensitive DNA or RNA detection. We also constructed a low-cost reusable 3D printed heater chassis and reusable sodium acetate heat packs for field use without generating solid waste.
Structural and functional analysis of YopR and identification of an additional key component of the SPβ phage lysis-lysogeny management system
Authors: Kohm Katharina , Jalomo-Khayrova Ekaterina , Basu Syamantak , Steinchen Wieland , Bange Gert , Hertel Robert , Commichau Fabian M. , Czech Laura 
Published: October 2022

ABSTRACTProphages need to tightly control their lifestyle to either be maintained within the host genome or enter the lytic cycle. The SPβ prophage present in the genome ofBacillus subtilis168 was recently shown to possess anarbitriumsystem defining its replication stage. Using an historicB. subtilisstrain harboring the heat-sensitive SPβ c2 mutant, we analyzed a key component of the lysis-lysogeny decision system called YopR, which is critical for maintenance of lysogeny. Here, we demonstrate that the heat-sensitive SPβ c2 phenotype is due to a single nucleotide exchange in theyopRgene, rendering the encoded YopRG136Eprotein temperature sensitive. Structural characterization of YopR revealed that the protein is a DNA-binding protein with an overall fold like tyrosine recombinases. Biochemical and functional analyses indicate that YopR has lost the recombinase function and the G136E exchange impairs its higher order structure and DNA binding activity. We further show that the heat-inducible SPβ excision of the c2 mutant still depends on the serine recombinase SprA. Finally, an evolution experiment identified the YosL protein of unknown function as a novel component of the lysis-lysogeny management system, as the presence ofyosLis crucial for the induction of the lytic cycle of SPβ.