bluuebunny/crossref_metadata_2025_split huggingface dataset:
OpNAC1 transcription factor regulates the biosynthesis of the anticancer drug camptothecin by targeting loganic acid O‐methyltransferase in Ophiorrhiza pumila
Authors: Hao Xiaolong , Wang Can , Zhou Wei , Ruan Qingyan , Xie Chenhong , Yang Yinkai , Xiao Chengyu , Cai Yan , Wang Jingyi , Wang Yao , Zhang Xuebin , Maoz Itay , Kai Guoyin 
Published: October 2022

ABSTRACTCamptothecin (CPT) is an anticancer pentacyclic quinoline alkaloid widely used to treat cancer patients worldwide. However, the biosynthetic pathway and transcriptional regulation of camptothecin are largely unknown. Ophiorrhiza pumila, the herbaceous plant from the Rubiaceae family, has emerged as a model plant for studying camptothecin biosynthesis and regulation. In this study, a high‐quality reference genome of O. pumila with estimated size of ~456.90 Mb was reported, and the accumulation level of camptothecin in roots was higher than that in stems and leaves. Based on its spatial distribution in the plant, we examined gene functions and expression by combining genomics with transcriptomic analysis. Two loganic acid O‐methyltransferase (OpLAMTs) were identified in strictosidine‐producing plant O. pumila, and enzyme catalysis assays showed that OpLAMT1 and not OpLAMT2 could convert loganic acid into loganin. Further knock‐out of OpLAMT1 expression led to the elimination of loganin and camptothecin accumulation in O. pumila hairy roots. Four key residues were identified in OpLAMT1 protein crucial for the catalytic activity of loganic acid to loganin. By co‐expression network, we identified a NAC transcription factor, OpNAC1, as a candidate gene for regulating camptothecin biosynthesis. Transgenic hairy roots and biochemical assays demonstrated that OpNAC1 suppressed OpLAMT1 expression. Here, we reported on two camptothecin metabolic engineering strategies paving the road for industrial‐scale production of camptothecin in CPT‐producing plants.
Navigating Uncertainty: A Case Study of Intrahepatic Cholestasis of Pregnancy
Authors: Blumenfeld Julie , Koo Kristin 
Published: October 2022

AbstractIntrahepatic cholestasis of pregnancy (ICP), the most common liver disorder of pregnancy, is associated with complications for both a pregnant person and their fetus. The underlying cause is not well understood. The pruritus associated with ICP is uncomfortable for pregnant people; however, the primary concern is the fetal risk. Fetal risks include preterm labor and birth and intrauterine fetal demise. This is particularly significant for certain populations because of the disparities in incidence of ICP; in the United States, it disproportionately affects Latinx people, the largest and fastest‐growing minority population. Diagnosis, monitoring, and treatment of ICP are vital to reduce discomfort from pruritis and avoid potential fetal demise. However, diagnosis and treatment are complicated by the lack of definitive diagnostic criteria, the frequent delay in laboratory analysis, and the cost of treatment. This case report aims to improve midwives’ familiarity with ICP and discusses the epidemiology, risk factors, presentation, diagnostic criteria, and available management strategies for this disease as well as the importance of anticipatory guidance regarding increased lifetime risk of ICP in future pregnancies and hepatobiliary disease. Additionally, it discusses the challenges involved in diagnosis and access to treatment. Prompt diagnosis and initiation of treatment may reduce fetal morbidity and mortality.
The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers
Authors: Harris Rachael , Beatty Caroline J. , Cori Jennifer M. , Spitz Gershon , Soleimanloo Shamsi Shekari , Peterson Scott A. , Naqvi Aqsa , Barnes Maree , Downey Luke A. , Shiferaw Brook A. , Anderson Clare , Tucker Andrew J. , Clark Anna , Rajaratnam Shantha M. W. , Howard Mark E. , Sletten Tracey L. , Wolkow Alexander P. ,   the National Transport Commission Heavy Vehicle Driver Fatigue Project Team
Published: October 2022

SummaryThis study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs’ sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.
A Phytophthora capsiciRXLR effector manipulates plant immunity by targeting RAB proteins and disturbing the protein trafficking pathway
Authors: Li Tianli , Ai Gan , Fu Xiaowei , Liu Jin , Zhu Hai , Zhai Ying , Pan Weiye , Shen Danyu , Jing Maofeng , Xia Ai , Dou Daolong 
Published: October 2022

AbstractThe oomycete pathogen Phytophthora capsici encodes hundreds of RXLR effectors that enter the plant cells and suppress host immunity. Only a few of these genes are conserved across different strains and species. Such core effectors might target hub genes and immune pathways in hosts. Here, we describe the functional characterization of the core P. capsici RXLR effector RXLR242. The expression of RXLR242 was up‐regulated during infection, and its ectopic expression in Nicotiana benthamiana, an experimental plant host, further promoted Phytophthora infection. RXLR242 physically interacted with a group of RAB proteins that belong to the small GTPase family and play a role in regulating transport pathways in the intracellular membrane trafficking system. In addition, RXLR242 impeded the secretion of PATHOGENESIS‐RELATED 1 (PR1) protein to the apoplast. This phenomenon resulted from the competitive binding of RXLR242 to RABE1‐7. We also found that RXLR242 interfered with the association between RABA4‐3 and its binding protein, thereby disrupting the trafficking of the membrane receptor FLAGELLIN‐SENSING 2. Thus, RXLR242 manipulates plant immunity by targeting RAB proteins and disrupting protein trafficking in the host plants.
Experimental infection of Aedes (Stegomyia) albopictus and Culex pipiens mosquitoes with Bluetongue virus
Authors: Ledda Salvatore , Foxi Cipriano , Puggioni Giantonella , Bechere Roberto , Rocchigiani Angela Maria , Scivoli Rosario , Coradduzza Elisabetta , Cau Simona , Vento Luigi , Satta Giuseppe 
Published: October 2022

AbstractBluetongue disease (BT), caused by Bluetongue virus (BTV), infects wild and domestic ruminants, causing severe economic damage in the cattle and sheep industry. Proven vectors of BTV are biting midges belonging to the Culicoides genus, but other arthropods are considered potential vectors, such as ticks, mosquitoes, wingless flies, and sand flies. The present study represents the first attempt to evaluate the vectorial capacity of Culex pipiens and Aedes albopictus for BTV. Mosquitoes were artificially fed with blood containing BTV serotype 1. Infection, dissemination and transmission rates were evaluated at 0, 3, 7, 14 and 21 days after an infected blood meal. Viral RNA was only detected up to 3 days post infection in the bodies of both species. This study indicates that the two Italian populations of Cx. pipiens and Ae. albopictus are not susceptible to BTV infection.
Systematic review of small intestine pacing parameters for modulation of gut function
Authors: Nagahawatte Nipuni D. , Cheng Leo K. , Avci Recep , Angeli‐Gordon Timothy R. , Paskaranandavadivel Niranchan 
Published: October 2022

AbstractBackground and PurposeThe efficacy of conventional treatments for severe and chronic functional motility disorders remains limited. High‐energy pacing is a promising alternative therapy for patients that fail conventional treatment. Pacing primarily regulates gut motility by modulating rhythmic bio‐electrical events called slow waves. While the efficacy of this technique has been widely investigated on the stomach, its application in the small intestine is less developed. This systematic review was undertaken to summarize the status of small intestinal pacing and evaluate its efficacy in modulating bowel function through preclinical research studies.MethodsThe literature was searched using Scopus, PubMed, Ovid, Cochrane, CINAHL, and Google Scholar. Studies investigating electrophysiological, motility, and/or nutrient absorption responses to pacing were included. A critical review of all included studies was conducted comparing study outcomes against experimental protocols.ResultsThe inclusion criteria were met by 34 publications. A range of pacing parameters including amplitude, pulse width, pacing direction, and its application to broad regional small intestinal segments were identified and assessed. Out of the 34 studies surveyed, 20/23 studies successfully achieved slow‐wave entrainment, 9/11 studies enhanced nutrient absorption and 21/27 studies modulated motility with pacing.ConclusionSmall intestine pacing shows therapeutic potential in treating disorders such as short bowel syndrome and obesity. This systematic review proposes standardized protocols to maximize research outcomes and thereby translate to human studies for clinical validation. The use of novel techniques such as high‐resolution electrical, manometric, and optical mapping in future studies will enable a mechanistic understanding of pacing.
What Is the Normal Trajectory of C‐Reactive Protein, Erythrocyte Sedimentation Rate, Plasma Fibrinogen and D‐Dimer after Two‐Stage Exchange for Periprosthetic Joint Infection?
Authors: Wu Yuangang , Zhou Jinhan , Liu Ran , Zeng Yi , Sun Kaibo , Li Mingyang , Peng Linbo , Xu Jiawen , Shen Bin 
Published: October 2022

ObjectiveC‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and D‐Dimer are used as diagnostic biomarkers of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of the study was to investigate the normal trajectory of CRP, ESR, plasma fibrinogen and D‐Dimer at different time points after two‐stage exchange arthroplasty for PJI.MethodsWe studied 53 patients undergoing two‐stage exchange for PJI at five time points: preoperatively (T0), duration of hospital stays (T1), 30 days (T2), 30–90 days (T3), and 90–180 days (T4) after surgery. The medical records of all patients were well documented and carefully reviewed. The Shapiro–Wilk test was utilized to compare the normal distribution for continuous variables, and the nonnormally distributed data were used for Friedmann's one‐way repeat measures analysis of variances. Post hoc Dunnett's test was used to compare each pair of data to find differences from baseline.ResultsCompare with T0 point, the levels of CRP and ESR increased significantly and reached peak values at T1 point (all P < 0.001), with median values of 56.40 mg/L (range, 5.54–161.0 mg/L) and 49.00 mm/h (range, 13.00–113.0 mm/h), respectively. In addition, the levels of plasma fibrinogen and D‐Dimer increased significantly and reached peak values at T1 point (all P < 0.001), with median values of 4.13g/L (range, 2.27–6.80 mg/L) and 4.00 mg/L (range, 0.19–14.01 mg/L), respectively. CRP and ESR rapidly declined at the T2 point with significantly compared with T0 point (P = 0.001 and P < 0.001). The levels of CRP, ESR, plasma fibrinogen and D‐Dimer returned to preoperative levels of 5.23 mg/L (range, 1.01–21.70 mg/L), 19.00 mm/h (range, 6.00–60.00 mm/h), 3.38g/L (range, 1.71–5.10 g/L) and 2.33 mm/h (range, 0.19–6.87 mg/L) at T4 point, and there was no significant difference compared with T0 point (all P > 0.05).ConclusionsThe study demonstrated the normal trajectory of CRP, ESR, plasma fibrinogen and D‐Dimer at five time points in patients who underwent two‐stage exchange for PJI. Thus, the results have the possibility of providing signs of infection after the patient receives two‐stage exchange arthroplasty for PJI, which can benefit from early treatment.
Feasibility of a novel algorithm for automated reconstruction of the left atrial anatomy based on intracardiac echocardiography
Authors: Akerström Finn , Drca Nikola , Jensen‐Urstad Mats , Braunschweig Frieder 
Published: October 2022

AbstractBackgroundIntracardiac echocardiography (ICE) is frequently used to guide electrophysiology procedures. The novel automated algorithm Cartosoundfam is a model‐based algorithm which reconstructs a 3D anatomy of the left atrium (LA) based on a set of 2D intracardiac echocardiography (ICE) frames, without the need to manually annotate ultrasound (US) contours.ObjectiveThe aim of this study was to determine the feasibility of the Cartosoundfam module in routine clinical setting.MethodsWe included 16 patients undergoing LA mapping/catheter ablation. Two‐dimensional US frames were acquired from the right atrium (RA) and the right ventricular outflow tract. The Cartosoundfam map was validated in two steps: (1) identification of anatomical structures (pulmonary veins [PV] and LA body and appendage) by alignment of the ablation catheter to the automated map; and (2) analysis of the automated lesion tags (Visitag) location in relation to the PV antrum of the Cartosoundfam map in nine patients with paroxysmal atrial fibrillation (AF) undergoing first time pulmonary vein isolation (PVI).ResultsMean 2D US frames per patient were 29 ± 6 and acquisition time was 16 ± 4 min. All anatomical structures were correctly identified in all patients (step 1). In the step 2 validation, the median distance to the map was 2.0 (IQR: 2.4) mm and the majority of the Visitags were classified as satisfactory (69%) but all PV segments had some Visitags classified as unsatisfactory.ConclusionThe automated ICE‐based algorithm correctly identified the LA anatomical structures in all patients with a 69% anatomical accuracy of the Visitags alignments to the PV antrum segments.
Oxidative stress, DNA damage, and histological alterations in Bombyx mori exposed orally to pesticide dimethoate
Authors: Qadri Hashim Ashraf , Qamar Ayesha , Maheshwari Nikhil 
Published: October 2022

AbstractPesticides are an essential part of agricultural practices that ward off pathogens and diseases from the agricultural crop. However, apart from target organisms, these chemicals also have adverse effects on non‐target organisms. Dimethoate is an insecticide used extensively in agriculture and horticulture practices worldwide. We used the silkworm Bombyx mori as a model organism to study the effect of commercial formulation of dimethoate (Dimethoate‐30% EC) on the gut, silk gland, and fat body tissues. LD50 of dimethoate‐30% EC on silkworm (B. mori) was 997 ppm, as reported in a previous study. We used concentrations of 25, 50, and 100 ppm in our experiments. Our results showed that sub‐lethal doses of dimethoate caused weight loss and induced damage at the histological level to the mid‐gut, silk gland, and fat body of B. mori. It also caused a decrease in the level of antioxidants like CAT, SOD, GPx, GSH, and GST, indicating that dimethoate has produced a shift of ROS balance towards free radical generation and therefore resulted in overall damage to this organism. Sub‐lethal doses of this pesticide also caused lipid peroxidation in the silk gland, gut, and fat body of B. mori, damaging these tissues. The disruption was also seen in the mid‐gut and middle silk gland at the DNA level, where it caused single‐strand breaks, as was revealed by single cell gel electrophoresis studies. Damage at histological, biochemical, and molecular levels was most extreme at a concentration of 100 ppm, the highest sub‐lethal concentration given to B. mori.
An anatomy of the impact of COVID‐19 on the global and intra‐Commonwealth trade in goods
Authors: Khorana Sangeeta , Martínez‐Zarzoso Inmaculada , Ali Salamat 
Published: October 2022

AbstractThis article employs gravity modeling to examine the effect of COVID‐19 on global and intra‐Commonwealth trade. It uses bilateral monthly exports, number of COVID‐19 cases and deaths and the stringency of measures. The main novelty is the use of price indices as proxies for multilateral resistance terms, which allow us to identify, supply, and demand effects of COVID‐19 on bilateral trade. The incidence of COVID‐19 impacts Commonwealth trade flows, the effect varies with the development level. High numbers of COVID‐19 cases, including deaths, in low‐income importers reduced Commonwealth exports unlike high‐income importers that show higher exports. The incidence of COVID in an exporters' neighbouring countries impacted trade and restrictions in high‐income countries increased Commonwealth trade. Short‐term trends project a negative change in both exports and imports of Commonwealth countries.
Associations between Contraceptive Decision‐Making and Marital Contraceptive Communication and use in Rural Maharashtra, India
Authors: Nazarbegian Melody , Averbach Sarah , Johns Nicole E. , Ghule Mohan , Silverman Jay , Lundgren Rebecka , Battala Madhusudana , Begum Shahina , Raj Anita 
Published: October 2022

AbstractWomen's contraceptive decision‐making control is crucial for reproductive autonomy, but research largely relies on the Demographic and Health Survey (DHS) measure which asks who is involved with decision‐making. In India, this typically assesses joint decision‐making or male engagement. Newer measures emphasize female agency. We examined three measures of contraceptive decision‐making, the DHS and two agency‐focused measures, to assess their associations with marital contraceptive communication and use in rural Maharashtra, India. We analyzed follow‐up survey data from women participating in the CHARM2 study (n = 1088), collected in June–December 2020. The survey included the DHS (measure 1), Reproductive Decision‐Making Agency (measure 2), and Contraceptive Final Decision‐Maker measures (measure 3). Only Measure 1 was significantly associated with contraceptive communication (adjusted odds ratio [AOR]: 2.75, 95 percent confidence interval [CI]: 1.69–4.49) and use (AOR: 1.73, 95 percent CI: 1.14–2.63). However, each measure was associated with different types of contraceptive use: Measure 1 with condom (adjusted relative risk ratio [aRRR]: 1.99, 95 percent CI: 1.12–3.51) and intrauterine device (IUD) (aRRR: 4.76, 95 percent CI: 1.80–12.59), Measure 2 with IUD (aRRR: 1.64, 95 percent CI: 1.04–2.60), and Measure 3 with pill (aRRR: 2.00, 95 percent CI: 1.14—3.52). Among married women in Maharashtra, India, male engagement in decision‐making may be a stronger predictor of contraceptive communication and use than women's agency, but agency may be predictive of types of contraceptives used.
Transfusion‐associated hyperkalemia in pediatric population: Analyses for risk factors and recommendations
Authors: Yamada Chisa , Edelson Maureen F. , Lee Angela C. , Saifee Nabiha H. , Dinov Ivo D. 
Published: October 2022

AbstractBackgroundTransfusion‐associated hyperkalemia (TAH) is a potentially life‐threatening complication of red blood cell (RBC) transfusion. Previously, we reported features of RBC transfusions from 35 pediatric patients (TAH group) who had hyperkalemia with RBC transfusion in one‐year period at four facilities. In this study, we used multivariate analyses and artificial intelligence to compare the TAH group to newly collected control group (non‐TAH group) to identify factors associated with TAH occurrence.Study DesignA review of RBC transfusion with TAH was compared to non‐TAH group who did not develop TAH with RBC transfusion at each facility during the same one‐year period. The non‐TAH group included 12 patients each in 5 age groups. Wilcoxon rank‐sum tests recursive feature elimination, least absolute shrinkage, and selection operator (LASSO), and other artificial intelligence techniques were employed to identify the most salient features associated with predicting specific clinical outcomes for TAH occurrence.Results/FindingsPre‐transfusion creatinine, comorbidities of kidney and/or liver dysfunctions, and total transfused volume within 12 h (tV‐12) per kg and per estimated total blood volume (eTBV) showed statistically significant differences between TAH and non‐TAH groups. Multivariate analysis revealed the biggest factor in TAH occurrence was tV‐12/kg followed by age of RBC units. The thresholds of risks were tV‐12/kg of 30 ml/kg, tV‐12/eTBV of 30%, and RBC unit age of 7.95 days.ConclusionsThe study findings suggest that the biggest factor on TAH occurrence is tV‐12/kg. More importantly, 30% of eTBV transfusion could cause TAH in patients with multiple comorbidities.
Association between initiation of fluoroquinolones and hospital admission or emergency department visit for suicidality: population based cohort study
Authors: Wang Junyi , Gagne Joshua J , Kattinakere-Sreedhara Sushama , Fischer Michael A , Bykov Katsiaryna 
Published: October 2022

Abstract

Objective
To evaluate the association between initiation of fluoroquinolones and hospital admission or emergency department visit for suicidality.

Design
Population based cohort study.

Setting
IBM MarketScan database, USA.

Participants
2 756 268 adults (≥18 years) who initiated an oral fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, ofloxacin, gatifloxacin, norfloxacin, lomefloxacin, besifloxacin) or comparator antibiotic (January 2003 to September 2015) and had at least six months of continuous health plan enrollment and a diagnosis of pneumonia or urinary tract infection (UTI) three days or less before the drug initiation date. Comparator antibiotics were azithromycin in the pneumonia cohort and trimethoprim-sulfamethoxazole in the UTI cohort. Participants were matched 1:1 within each cohort on a propensity score, calculated from a multivariable logistic regression model that included 57 baseline covariates.

Main outcomes measure
Primary outcome was hospital admission or emergency department visit for suicidal ideation or self-harm within 60 days after treatment initiation. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals.

Results
The pneumonia cohort included 551 042 individuals, and the UTI cohort included 2 205 526 individuals. During the 60 day follow-up, 181 events were observed in the pneumonia cohort and 966 in the UTI cohort. The adjusted hazard ratios for fluoroquinolones were 1.01 (95% confidence interval 0.76 to 1.36) versus azithromycin in the pneumonia cohort and 1.03 (0.91 to 1.17) versus trimethoprim-sulfamethoxazole in the UTI cohort. Results were consistent across sensitivity analyses and subgroups of sex, age, or history of mental illnesses.

Conclusion
Initiation of fluoroquinolones was not associated with a substantially increased risk of admission to hospital or emergency department visits for suicidality compared with azithromycin or trimethoprim-sulfamethoxazole.