bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mirror-Image Comparison of Maintenance Electroconvulsive Treatment Effectiveness in Affective and Psychotic Disorders
Authors: Bağcaz Arda , Başar Koray 
Published: June 2022

Objectives
The study aimed to investigate the effectiveness of maintenance electroconvulsive therapy (mECT) with respect to the hospitalization duration, number of hospitalizations, and major and minor treatment changes with a mirror-image study design.

Methods
Medical charts of patients who received at least a 3-month-long course of mECT were reviewed. The records of 36 patients (17 with psychotic disorders, 19 with affective disorders) were retrospectively examined for 2 periods with the same duration; during the mECT (post-mECT) and before the mECT (pre-mECT). The hospitalization duration, the number of hospitalizations, and major and minor treatment changes, which were assumed to provide information on the effectiveness of the interventions, were recorded and compared between these periods. Statistical analysis was performed using generalized estimating equation models conducted with age, diagnostic category, and observation time as covariates. In addition, the relapse and recurrence rates and time to relapse/recurrence were analyzed.

Results
Comparison of pre-mECT and post-mECT periods revealed that mECT, applied in an individualized schedule combined with pharmacotherapy, was associated with a lower frequency (P < 0.001; rate ratio [RR], 0.161; 95% confidence interval [CI], 0.087–0.297), shorter duration of hospitalization (P < 0.001; RR, 0.123; 95% CI, 0.056–0.271), and lower number of major treatment changes (P = 0.007; RR, 0.522; 95% CI, 0.324–0.840), irrespective of diagnoses. The relapse/recurrence rates were similar in the 2 diagnostic categories (P = 1.000; 26.3% vs 29.4%).

Conclusions
Maintenance ECT should be increasingly considered an important treatment modality in patients with affective and psychotic disorders after an effective course of ECT.
Whole genome sequencing of a wild yam species Dioscorea tokoro reveals a genomic region associated with sex
Authors: Natsume Satoshi , Yaegashi Hiroki , Sugihara Yu , Abe Akira , Shimizu Motoki , Oikawa Kaori , White Benjamen , Kudoh Aoi , Terauchi Ryohei 
Published: June 2022

AbstractDioscorea tokoro is a wild species distributed in East Asia including Japan. Typical of the genus Dioscorea, D. tokoro is dioecious with male and female flowers borne on separate individuals. To understand its sex determination system and to serve as a model species for population genomics of obligate outcrossing wild species, we set out to determine the whole genome sequence of the species. Here we show 443 Mb genome sequence of D. tokoro distributed over 2,931 contigs that were anchored on 10 linkage groups. Linkage analysis of sex in a segregating F1 family revealed a sex determination locus residing on Pseudochromosome 3 with XY-type male heterogametic sex determination system.
Impact of non-pharmaceutical interventions targeted at the COVID-19 pandemic on influenza activity in the UK Armed Forces
Authors: Otieno George , Rawlings Ngwa Niba 
Published: June 2022

AbstractIntroductionNon-pharmaceutical interventions (NPIs) such as lockdown, social distancing and use of face coverings was adopted by the United Kingdom (UK) Armed Forces (AF) during the COVID-19 pandemic. This study assessed the impact of the use of NPIs on influenza activity in the UK AF.MethodsA longitudinal study design was adopted, and secondary data was analysed retrospectively. Clinical Read codes for influenza-like illness (ILI) was used to generate data for flu seasons before and during the COVID-19 pandemic (September 2017 to April 2021).ResultsBefore the COVID-19 pandemic, the rate of reporting ILI was ∼ 4% across all flu seasons. The count of ILI was 2.9%, 2.2% and 3.1% during 2017-18, 2018-19 and 2019-20 flu seasons respectively. During the COVID-19 pandemic, both the rate of reporting ILI (0.6%) and the count of ILI (0.5%) were significantly smaller (p < .001). The rate of reporting ILI was positively correlated with the count of ILI (r (2) = .97, p = .014). Influenza vaccination rate increased by 1.3% during the COVID-19 pandemic. vaccination rate was negatively correlated with the rate of reporting ILI (r (2) = -.52, p = 0.24) and the count of ILI (r (2) = -.61, p = 0.19). However, this correlation was not significant. The use of NPIs was negatively correlated with the rate of reporting ILI (r (2) = -.99, p = < .001) and the count of ILI (r (2) = -.95, p = 0.026). The overall multiple regression performed was statistically significant (R2= 0.94, F (1, 2) = 33.628, p = 0.028). The rate of reporting ILI significantly predicted the count of ILI (β = 0.609, p = 0.028) while vaccination rate did not significantly predict the count of ILI (β = -0.136, p = 0.677).ConclusionsInfluenza activity in the UK AF was significantly reduced during the COVID-19 pandemic. The use of NPIs and the rate of reporting ILI significantly reduced the count of ILI. Being vaccinated for influenza did not significantly reduce the count of ILI.
BRCA1/BRC-1 and SMC-5/6 regulate DNA repair pathway engagement during C. elegans meiosis
Authors: Toraason Erik , Salagean Alina , Almanzar David E. , Rog Ofer , Libuda Diana E. 
Published: June 2022

AbstractThe preservation of genome integrity during sperm and egg development is vital for reproductive success. During meiosis, the tumor suppressor BRCA1/BRC-1 and structural maintenance of chromosomes 5/6 (SMC-5/6) complex genetically interact to promote high fidelity DNA double strand break (DSB) repair, but the specific DSB repair outcomes these proteins regulate remain unknown. Here we show that BRCA1/BRC-1 and the SMC-5/6 complex limit intersister crossover recombination as well as error-prone repair pathways during meiotic prophase I. Using genetic and cytological methods to monitor repair of DSBs with different repair partners in Caenorhabditis elegans, we demonstrate that both BRC-1 and SMC-5/6 repress intersister crossover recombination events, with meiotic cells becoming more dependent upon these proteins to repair DSBs in late meiotic prophase I. Sequencing of conversion tracts from homolog-independent DSB repair events indicates that BRC-1 regulates intersister/intrachromatid noncrossover conversion tract length. Moreover, we find that BRC-1 also specifically inhibits error prone repair of DSBs induced at mid-pachytene. Finally, we reveal that functional BRC-1 enhances DSB repair defects in smc-5 mutants by repressing theta-mediated end joining (TMEJ). Taken together, our study illuminates the coordinate interplay of BRC-1 and SMC-5/6 to regulate DSB repair outcomes in the germline.
Distinct airway progenitor cells drive epithelial heterogeneity in the developing human lung
Authors: Conchola Ansley S. , Frum Tristan , Xiao Zhiwei , Hsu Peggy P. , Hein Renee F.C. , Miller Alyssa , Tsai Yu-Hwai , Wu Angeline , Kaur Kamika , Holloway Emily M. , Anand Abhinav , Murthy Preetish K. L. , Glass Ian , Tata Purushothama R. , Spence Jason R. 
Published: June 2022

ABSTRACTRecent advances using single cell genomic approaches have identified new epithelial cell types and uncovered cellular heterogeneity in the murine and human lung (1). Here, using scRNA-seq and microscopy we identify and describe a secretory-like cell that is enriched in the small airways of the developing human lung and identified by the unique co-expression of SCGB3A2/SFTPB/CFTR. To place these cells in the hierarchy of airway development, we apply a single cell barcode-based lineage tracing method track the fate of SCGB3A2/SFTPB/CFTR cells during airway organoid differentiation in vitro (2). Lineage tracing revealed that these cells have distinct developmental potential from basal cells, giving rise predominantly to pulmonary neuroendocrine cells (PNECs) and a subset of multiciliated cells distinguished by high C6 and low MUC16 expression. We conclude that SCGB3A2/SFTPB/CFTR cells act as a progenitor cell contributing to the cellular diversity and heterogeneity in the developing human airway.SIGNIFICANCE STATEMENTThe current study identifies a novel secretory cell type that is present predominantly in the small airway of the developing human lung. These secretory cells are defined by co-expression of SCGB3A2/SFTPB/CFTR, and functional studies show that this cell gives rise to pulmonary neuroendocrine cells and a sub-population of multiciliated cells, thereby leading to cellular heterogeneity.
Enzymatic Specificity of Conserved Rho GTPase Deamidases Promotes Invasion ofVibrio parahaemolyticusat the Expense of Infection
Authors: Lafrance Alexander E. , Chimalapati Suneeta , Rodriguez Nalleli Garcia , Kinch Lisa N. , Kaval Karan Gautam , Orth Kim 
Published: June 2022

AbstractVibrio parahaemolyticusis among the leading causes of bacterial seafood-borne acute gastroenteritis. Like many intracellular pathogens,V. parahaemolyticusinvades host cells during infection by deamidating host small Rho GTPases. The Rho GTPase deamidating activity of VopC, a type three secretion system (T3SS) translocated effector, drivesV. parahaemolyticusinvasion. The intracellular pathogen uropathogenicEscherichia coli(UPEC) invades host cells by secreting a VopC homolog, the secreted toxin cytotoxic necrotizing factor one (CNF1). Because of the homology between VopC and CNF1, we hypothesized topical application of CNF1 duringV. parahaemolyticusinfection could supplement VopC activity. Here, we demonstrate that CNF1 improves the efficiency ofV. parahaemolyticusinvasion, a bottleneck inV. parahaemolyticusinfection, across a range of doses. CNF1 increasesV. parahaemolyticusinvasion independent of both VopC and the T3SS altogether, but leaves a disproportionate fraction of intracellular bacteria unable to escape the endosome and complete their infection cycle. This phenomenon holds true in the presence or absence of VopC, but is particularly pronounced in the absence of a T3SS. The native VopC, by contrast, promotes a far less efficient invasion, but permits the majority of internalized bacteria to escape the endosome and complete their infection cycle. These studies highlight the significance of enzymatic specificity during infection, as virulence factors (VopC and CNF1 in this instance) with similarities in function (bacterial uptake), catalytic activity (deamidation), and substrates (Rho GTPases) are not sufficiently interchangeable for mediating a successful invasion for neighboring bacterial pathogens.IMPORTANCEMany species of intracellular bacterial pathogens target host small Rho-GTPases to initiate invasion, including the human pathogensVibrio parahaemolyticusand uropathogenicEschericia coli(UPEC). The type three secretion system (T3SS) effector VopC ofV. parahaemolyticuspromotes invasion through the deamidation of Rac1 and CDC42 in the host, whereas the secreted toxin cytotoxic necrotizing factor one (CNF1) drives UPEC’s internalization through the deamidation of Rac1, CDC42, and RhoA. Despite these similarities in the catalytic activity of CNF1 and VopC, we observed the two enzymes were not interchangeable. Although CNF1 increasedV. parahaemolyticusendosomal invasion, most intracellularV. parahaemolyticusaborted their infection cycle and remained trapped in endosomes. Our findings illuminate how the precise biochemical fine-tuning of T3SS effectors is essential for efficacious pathogenesis. They moreover pave the way for future investigations into the biochemical mechanisms underpinningV. parahaemolyticusendosomal escape, and more broadly, the regulation of successful pathogenesis.
Helicobacter pylori chronic infection selects for effective colonizers of metaplastic glands
Authors: O’Brien VP , Jackson LK , Frick JP , Rodriguez Martinez AE , Jones DS , Johnston CD , Salama NR 
Published: June 2022

AbstractChronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to induce proliferation and alter the expression of metaplasia-associated proteins. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB strongly reduced adherence to both normal and metaplastic gastric tissue in multiple strain backgrounds and highly attenuated stomach colonization. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization.ImportanceChronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.
A data-driven approach to identify clusters of HbA1c longitudinal trajectories and associated outcomes in type 2 diabetes mellitus: a large population-based cohort study
Authors: la Torre Adrian Martinez-De , Faquetti Maria Luisa , Perez-Cruz Fernando , Meier Christian , Weiler Stefan , Burden Andrea M. 
Published: June 2022

AbstractBackgroundWe aimed to identify and characterize common patterns of HbA1c progression among type 2 diabetes mellitus patients who initiate a non-insulin antidiabetic drug (NIAD).MethodsThe IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records, was used to identify a cohort of patients with a first-ever prescription for a NIAD between 2006 and 2019. Trajectory clusters were identified using an Expectation-Maximization algorithm by iteratively fitting k thin-plate splines and reassigning each patient to the nearest cluster. Cox proportional hazards models calculated the hazard ratios (HR) and 95% confidence intervals (CI) for the estimated risk of microvascular (e.g., retinopathy, diabetic polyneuropathy [DPN]) and macrovascular events.FindingsAmong 116,251 new users of NIADs we found five distinct clusters of HbA1c progression, which were characterized as: optimally controlled (OC), adequately controlled (AC), sub-optimally controlled (SOC), poorly controlled (PC), and uncontrolled (UC). The UC and AC clusters had similar index HbA1C (>9%) but the AC cluster achieved HbA1c control (HbA1C <7.5%), while the UC cluster HbA1c remained >9.0%. Compared to the OC cluster, there was a 21% (HR: 1.21, 95% CI: 1.14-1.28) and 30% (HR: 1.30, 95% CI: 1.21-1.40) elevated risk of retinopathy in the AC and UC clusters, respectively. While the PC and UC clusters had a significant 23% (HR 1.23, 95% CI 1.12 – 1.35) and 45% (HR 1.45, 95% CI: 1.27 – 1.64) increased risk of DPN, respectively.InterpretationThe five identified HbA1c trajectory clusters had different risk profiles. Despite achieving diabetic control, patients categorized in the AC cluster had similar outcomes to the UC cluster, suggesting baseline HbA1c is an important indicator of health outcomes.FundingThe Swiss Data Science Centre
Genetic mining of newly isolated Salmophages for phage therapy
Authors: Gendre J. , Ansaldi M. , Olivenza D.R. , Denis Y. , Casadesús J. , Ginet N. 
Published: June 2022

I.ABSTRACTSalmonella enterica - a Gram negative zoonotic bacterium – is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. Main reservoirs are found in poultry farms but also in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here we aimed at deciphering and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. We finally searched for useful functions for phage therapy such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRIPSR proteins. We thus were able to genetically characterized nine virulent phages and one temperate phage and identified putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol.
Dual role of Pectin Methyl Esterase activity in the regulation of plant cell wall biophysical properties
Authors: Gallemí Marçal , Montesinos Juan Carlos , Zarevski Nikola , Pribyl Jan , Skládal Petr , Hannezo Edouard , Benková Eva 
Published: June 2022

ABSTRACTAcid-growth theory has been postulated in the 70s to explain the rapid elongation of cells in response to plant hormone auxin. More recently, it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting acidification of the apoplast is the principal mechanism through which hormones like auxin as well as brassinosteroids (BR) induce cell elongation. However, the impact of this acidification on the mechanical properties of the cell wall remained largely unexplored. Here, we use Atomic Force Microscopy (AFM) to demonstrate that acidification of apoplast is necessary and sufficient to induce cell elongation through cell wall relaxation. Moreover, we demonstrate that Pectin Methyl Esterase (PME) can induce both cell wall softening or stiffening in extracellular calcium dependent-manner and that tight control of PME activity is required for hypocotyl elongation.
Genomic, transcriptomic, and metabolomic analysis of Traditional Chinese Medicine plantOldenlandia corymbosareveals the biosynthesis and mode of action of anti-cancer metabolites
Authors: Julca Irene , Mutwil-Anderwald Daniela , Manoj Vaishnervi , Khan Zahra , Lai Soak Kuan , Yang Lay Kien , Beh Ing Tsyr , Dziekan Jerzy , Lim Yoon Pin , Lim Shen Kiat , Low Yee Wen , Lam Yuen In , Mu Yuguang , Tan Qiao Wen , Nuc Przemyslaw , Choo Le Min , Khew Gillian , Shining Loo , Kam Antony , Tam James P. , Bozdech Zbynek , Schmidt Maximilian , Usadel Bjoern , Kanagasundaram Yoganathan s/o , Alseekh Saleh , Fernie Alisdair , Yeung Li Hoi , Mutwil Marek 
Published: June 2022

AbstractNatural products from traditional medicinal plants are valuable candidates for clinical cancer therapy. Plants from the Oldenlandia-Hedyotis complex are popular ingredients of Traditional Chinese Medicine (TCM), however a major hurdle in the plant bioprospecting process of TCM plants is that the active metabolites, their biosynthetic pathways, and mode of action are often unknown. We show thatOldenlandia corymbosaextracts are active against breast cancer cell lines. To study the genes involved in the biosynthesis of active compounds in this medicinal plant, we assembled a high-quality genome. We show that the main active compound is ursolic acid and that abiotic stresses cause changes in anti-cancer activity, metabolite composition, and gene expression of plants. To reveal the mode of action of ursolic acid, we show that cancer cells undergo mitotic catastrophe, and we identify three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking.
Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
Authors: Park Daehun , Wu Yumei , Baublis Aaron , De Camilli Pietro 
Published: June 2022

AbstractEctopic expression in fibroblasts of synapsin 1 and synaptophysin is sufficient to generate condensates of vesicles highly reminiscent of synaptic vesicle (SV) clusters and with liquid-like properties. We show that unlike synaptophysin, other major integral SV membrane proteins fail to form condensates with synapsin, but coassemble into the clusters formed by synaptophysin and synapsin in this ectopic expression system. Another vesicle membrane protein, ATG9A, undergoes activity-dependent exo-endocytosis at synapses, raising questions about the relation of ATG9A traffic to the traffic of SVs. We have found that both in fibroblasts and in nerve terminals ATG9A does not coassemble into synaptophysin-positive vesicle condensates but localizes on a distinct class of vesicles that also assembles with synapsin but into a distinct phase. Our findings suggest that ATG9A undergoes differential sorting relative to SV proteins and also point to a dual role of synapsin in controlling clustering at synapses of SVs and ATG9A vesicles.
Nutrient limitation mimics artemisinin tolerance in malaria
Authors: Brown Audrey , Warthan Michelle D , Aryal Anush , Liu Shiwei , Guler Jennifer L 
Published: June 2022

AbstractMounting evidence demonstrates that nutritional environment can alter pathogen drug sensitivity. While the nutrient-rich media used for standard in vitro culture contains supra-physiological nutrient concentrations, pathogens encounter a relatively restrictive environment in vivo. We assessed the effect of nutrient limitation on the protozoan parasite that causes malaria and demonstrated that short-term growth under physiologically-relevant mild nutrient stress (or “metabolic priming”) triggers increased tolerance of the potent antimalarial drug dihydroartemisinin (DHA). We observed beneficial effects using both short-term survival assays and longer-term proliferation studies, where metabolic priming increases parasite survival to a level previously defined as DHA resistant (>1% survival). We performed these assessments by either decreasing single nutrients that have distinct roles in parasite metabolism or using a media formulation with reductions in many nutrients that simulates the human plasma environment. We determined that priming-induced DHA tolerance was restricted to parasites that had newly invaded the host red blood cell but the effect was not dependent on genetic background. The molecular mechanisms of this intrinsic effect mimic aspects of genetic artemisinin tolerance, including translational repression, autophagy, and protein export. This finding suggests regardless of the impact on survival rates, environmental stress could stimulate changes that ultimately directly contribute to drug tolerance. Because metabolic stress is likely to occur more frequently in vivo compared to the stable in vitro environment, priming-induced drug tolerance has ramifications for how in vitro results translate to in vivo studies. Improving our understanding of how pathogens adjust their metabolism to impact survival of current and future drugs is an important avenue of research to prevent and slow the spread of resistance.