bluuebunny/crossref_metadata_2025_split huggingface dataset:
MDR1 Polymorphisms and Modulation of ARV Drug Induced Hepatotoxicity
Authors: SINGH HARI OM , Samani Dharmesh 
Published: November 2021

Abstract
Background

Antiretroviral (ARV) regimen is used to manage the progression of HIV infection. MDR1 Polymorphism is associated with the treatment outcome. Ethnic disparities have been observed in the distribution of MDR1 genotypes. Hence we analyzed the association of MDR1 polymorphism with the modulation of ARV associated hepatotoxicity.MDR1 polymorphisms (1236 C/T, 3435 C/T) was genotyped in a total 165 HIV-infected individuals (34 ARV drug induced hepatotoxicity were labeled as cases, 131 those without hepatotoxicity were controls) and 155 healthy individuals by utilization of PCR-RFLP.
Results

Individuals with haplotype TC of MDR1 were at greater risk for hepatotoxicity severity (OR=1.96, P=0.06). Haplotypes TT and CC were associated with a reduced risk of hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). MDR1 1236TT genotype was seen higher among ARV drug induced hepatotoxicity cases who consumed alcohol than non-users (28.6% versus 14.8%, OR=1.50). There was an increased prevalence of MDR1 1236TT genotype in ARV drug induced hepatotoxicity cases on nevirapine in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). The incidence of MDR1 1236CT, 1236TT genotypes was found to be more in individuals those without hepatotoxicity on nevirapine as compared to efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). MDR1 1236TT genotype in presence of nevirapine and who consumed alcohol showed risk for severity of hepatotoxicity (40.0% versus 16.67%, OR=2.21).
Conclusion

Haplotype TC was associated with hepatotoxicity severity. MDR1 1236TT and 3435CT genotypes in presence of nevirapine and who consume alcohol showed higher risk for acquisition and severity of ARV associated hepatotoxicity.
Italian Survey on Perception of Obesity and Bariatric and Metabolic surgery: a comparison between general practitioners and obese patients
Authors: Tassinari Daniele , Giassi Cecilia Lucia Andrea , Giovanelli Alessandro , De Santis Emanuela , Boveri Sara , Asteria Carmela 
Published: November 2021

Abstract
Purpose Obesity is a pandemic, chronic and relapsing disease with several treatment options. The aim of this work was to investigate the level of awareness that people with obesity (PwO) have of their own condition and the level of knowledge regarding possible treatments available. To compare and contrast collected data on PwO with data obtained from general practitioners (GPs). Methods Data for this cross-sectional, non-interventional, descriptive study was collected via an online survey (CAWI methodology). 521 people were interviewed: 320 PwO and 201 GPs. Survey data were summarised in percentages and a 95% Confidence Interval (CI 95%). Results There is a lack of awareness of obesity as a disease among PwO. Firstly, most PwO (60%, 95% CI: 54%-65%) consider obesity to be an aesthetic problem and secondly a health problem (59%, 95% CI: 54%-65%). Conversely, 80% (95% CI: 74%-85%) of GPs consider obesity as a disease. The survey focus on the knowledge of bariatric and metabolic surgery (BMS) as a possible treatment option showed that only 12% of PwO (95% CI: 8%-16%) declared they had never heard about it, while 88% (95% CI: 84%-91%) declared they knew about it. Similarly, 95% (95% CI: 91%-98%) of GPs claim to know about BMS, but they recommended it only to 5% (95% CI:2%-9%) of their patients. In treating obesity GPs considered BMS less efficient than diet and physical activity (83% (95% CI: 77%-88%) vs 90% (95% CI: 84%-93%)) and to be indicated mainly for patients with comorbidities which cannot be controlled otherwise. Conclusions Our results indicate that implementing awareness campaigns for patients and GPs is currently as essential as providing structured programmes for obesity treatment. Moreover, it is still necessary to sensitize GPs on BMS which should be considered a standard obesity treatment option in selected cases. Level of evidence: Level V, cross-sectional, descriptive study.
Too Much of a Good Thing? Inorganic Nitrogen (N) Inhibits Moss-Associated N2 Fixation But Organic N Can Promote It
Authors: Wang Yinliu , Lett Signe , Rousk Kathrin 
Published: November 2021

Abstract
Moss-associated nitrogen (N2) fixation is one of the main inputs of new N in pristine ecosystems that receive low amounts of atmospheric N deposition. Previous studies have shown that N2 fixation is inhibited by inorganic N (IN) inputs, but if N2 fixation in mosses is similarly affected by organic N (ON) remains unknown. Here, we assessed N2 fixation in two dominant mosses in boreal forests (Pleurozium schreberi and Sphagnum capillifolium) in response to different levels of N, simulating realistic (up to 4 kg N ha−1 yr−1) and extreme N deposition rates in pristine ecosystems (up to 20 kg N ha−1 yr−1) of IN (NH4NO3) and ON (alanine and urea). We also assessed if N2 fixation can recover from the N additions. In the realistic scenario, N2 fixation was inhibited by increasing NH4NO3 additions in P. schreberi but not in S. capillifolium, and alanine and urea stimulated N2 fixation in both moss species. In contrast, in the extreme N additions, increasing N inputs inhibited N2 fixation in both moss species and all N forms. Nitrogen fixation was more sensitive to N inputs in P. schreberi than in S. capillifolium and was higher in the recovery phase after the realistic compared to the extreme N additions. These results demonstrate that N2 fixation in mosses is less sensitive to organic than inorganic N inputs and highlight the importance of considering different N forms and species-specific responses when estimating the impact of N inputs on ecosystem functions such as moss-associated N2 fixation.
Correlation Between Maternal Weight Gain in Each Trimester and Fetal Growth According to Pre-pregnancy Maternal Body Mass Index in Twin Pregnancies
Authors: Kim Mi Ju , Kim Hyun Mi , Cha Hyun Hwa , Seong Won Joon 
Published: November 2021

Abstract
Background: This study aimed to determine the correlation between maternal weight gain in each trimester and fetal growth according to pre-pregnancy maternal body mass index in twin pregnancies.Methods: We conducted a retrospective review of the medical records of 500 twin pregnancies delivered at 28 weeks’ gestation or greater at a single tertiary center between January 2011 and December 2020. We measured the height, pre-pregnant body weight, and maternal body weight of women with twin pregnancies and evaluated the relationship between the maternal weight gain at each trimester and fetal growth restriction according to pre-pregnancy body mass index.Results: The overweight pregnant women were older than the normal or underweight pregnant women, and the risk of gestational diabetes was high. The underweight pregnant women were younger, and the incidences of preterm labor and short cervical length during pregnancy was high. Especially in normal weight pregnant women, the heavier the weight of the newborn babies as the second trimester of pregnancy weight gain, the less significant the weight gain in the first trimester of pregnancy and fetal growth. The most predictive single factor for the prediction of small neonates was weight gain during 24-28 weeks and 15-18 weeks, and the cutoff value was 6.2 kg. (area under the curve 0.592, p < 0.001).Conclusions: In twin pregnancy, regardless of the pre-pregnant body mass index, maternal weight gain affected fetal growth. Furthermore, weight gain in the second trimester of pregnancy is considered a powerful indicator of fetal growth, especially in normal weight pregnancies.
Treatment for right-sided intrathoracic kidney with congenital diaphragmatic hernia by combined thoracoscopic and laparoscopic approach: a case report and literature review
Authors: Yu Mingming , Chen Fang , Wei Sisi , Xie Hua 
Published: November 2021

Abstract
BackgroundIntrathoracic kidney (ITK) associated with congenital diaphragmatic hernia (CDH) is rare congenital anomaly and usually requires surgery. The surgical methods and approaches are diverse.Case presentationWe reported a case of a 5-year-old boy who was diagnosed as right-sided ITK with CDH. Surgical treatment was performed by combined thoracoscopic and laparoscopic approach. Anatomical reposition of the right kidney and nephropexy were carried out under laparoscopy, and repair of the hernia was performed under thoracoscopy. The postoperative recovery was uneventful and long-term follow-up demonstrated normal function and development of the kidney.ConclusionCombined thoracoscopic and laparoscopic approach is minimally invasive and effective for treatment of ITK associated with CDH. It provides better visualization of the diaphragmatic foramen and the hernia sac, and can achieve anatomical reposition and fixation of the ectopic kidney.
The Role of Procalcitonin in Predicting Risk of Mechanical Ventilation and Mortality among moderate to Severe COVID-19 Patients
Authors: Twe Cher Wei , Khoo Delton , Law Kian Boon , Nordin Nur Sabreena Ahmad , Sathasivan Subashini , Lim Kah Chuan , Atikah Sharifah Khairul , Badaruddin Syarifah Nurul Ain Syed , Chidambaram Suresh Kumar 
Published: November 2021

Abstract
BackgroundSerum procalcitonin (PCT) has become an emerging prognostic biomarker of disease progression in patients with COVID-19. This study aims to determine the optimal cut-off value of PCT with regards to important clinical outcomes, especially for mechanical ventilation and all-cause mortality among moderate to severe COVID-19 patients in Malaysia.MethodsA total of 319 moderate to severe COVID-19 patients hospitalized at the National Referral Hospital in December 2020 were included in the study retrospectively. Demographics, comorbidities, the severity of COVID-19 infection, laboratory and imaging findings, and treatment given were collected from the hospital information system for analysis. The optimal cut-point values for PCT were estimated in two levels. The first level involved 276 patients who had their PCT measured within 5 days following their admission. The second level involved 237 patients who had their PCT measured within 3 days following their admission. Further, a propensity score matching analysis was performed to determine the adjusted relative risk of patients with regards to various clinical outcomes according to the selected cut-point among 237 patients who had their PCT measured within 3 days. ResultsThe results showed that a PCT level of 0.2 ng/mL was the optimal cut-point for prognosis especially for mortality outcome and the need for mechanical ventilation. Before matching, patients with PCT ≥ 0.2ng/mL were associated with significantly higher odds in all investigated outcomes. After matching, patients with PCT > 0.2 ng/mL were associated with higher odds in all-cause mortality (OR: 4.629, 95% CI: 1.387 – 15.449, p = 0.0127) and non-invasive ventilation (OR: 2.667, 95% CI: 1.039 – 6.847, p = 0.0415). Furthermore, patients with higher PCT were associated with significantly longer days of mechanical ventilation (p = 0.0213). There was however no association between higher PCT level and the need for mechanical ventilation (OR: 2.010, 95% CI: 0.828 - 4.878, p = 0.1229).ConclusionOur study indicates that a rise in PCT above 0.2ng/ml is associated with an elevated risk in all-cause mortality, the need for non-invasive ventilation, and a longer duration of mechanical ventilation. The study offers concrete evidence for PCT to be used as a prognostication marker among moderate to severe COVID-19 patients.
A Novel Long Non-Coding RNA Regulates The Integrin, ITGA2 in Breast Cancer
Authors: Verhoeff Tristan J , Holloway Adele F , Dickinson Joanne L 
Published: November 2021

Abstract
Purpose
ITGA2 encodes the integrin, a2 which mediates metastatic progression, and is a predictor of poor prognosis and chemoresistance in breast cancer. Decreased ITGA2 promoter methylation is implicated as a driver of increased gene expression in aggressive prostate and pancreatic tumours, however the contribution of altered methylation to ITGA2 expression changes in breast tumours has not been examined.
Methods
ITGA2 gene methylation and gene expression was examined in publicly available breast cancer datasets, and ITGA2 promoter methylation was mapped by targeted bisulphite sequencing analysis in breast tumour cell lines. The expression of a putative regulatory long noncoding RNA (lncRNA) was examined by qPCR and its’ functionality was investigated using gene knockdown (antisense oligonucleotides) and over expression analysis in breast cancer cell lines.
Results
In breast tumours and breast cancer cell lines the ITGA2 promoter is largely unmethylated, with gene expression variable in tumour subtypes, irrespective of promoter methylation. A novel lncRNA (AC025180.1;ENSG00000249899), named herein I2ALR, was identified at the ITGA2 gene locus, and was variably expressed in breast tumours and breast cancer cell subtypes. I2LAR knockdown resulted in upregulation of ITGA2 gene expression, whilst over-expression of I2ALR resulted in downregulation of ITGA2 mRNA. Further, examination of two downstream targets of ITGA2 associated with breast tumor stemness and metastasis (CCND1 and ACLY), revealed concomitant gene expression changes in response to I2ALR modulation.
Conclusion
I2ALR represents a novel regulatory molecule targeting ITGA2 expression in breast tumours; a finding of significant and topical interest to the development of therapeutics targeting this integrin.
Functional and Mechanistic Characterization of an Enzyme Family Combining Bioinformatics and High-Throughput Microfluidics
Authors: Vasina Michal , Vanacek Pavel , Hon Jiri , Kovar David , Faldynova Hanka , Kunka Antonin , Badenhorst Christoffer , Buryska Tomas , Mazurenko Stanislav , Bednar David , Stavros Stavros , Bornscheuer Uwe , deMello Andrew , Damborsky Jiri , Prokop Zbynek 
Published: November 2021

Abstract
Next-generation sequencing doubles genomic databases every 2.5 years. The accumulation of sequence data raises the need to speed up functional analysis. Herein, we present a pipeline integrating bioinformatics and microfluidics and its application for high-throughput mining of novel haloalkane dehalogenases. We employed bioinformatics to identify 2,905 putative dehalogenases and selected 45 representative enzymes, of which 24 were produced in soluble form. Droplet-based microfluidics accelerates subsequent experimental testing up to 20,000 reactions per day while achieving 1,000-fold lower protein consumption. This resulted in doubling the dehalogenation “toolbox" characterized over three decades, yielding biocatalysts surpassing the efficiency of currently available enzymes. Combining microfluidics with modern global data analysis provided precious mechanistic information related to the high catalytic efficiency of new variants. This pipeline applied to other enzyme families can accelerate the identification of biocatalysts for industrial applications as well as the collection of high-quality data for machine learning.
Antibiotic Use and Appropriateness in the Treatment of Acute Respiratory Tract Infections in Tunisian Primary Care and Emergency Departments (Barometer Study): a Multicenter Cross-sectional Observational Clinical Study
Authors: Ali Khaoula Bel Haj , Sekma Adel , Messous Selma , Trabelsi Imen , Youssef Jalel Ben , Maghraoui Hamida , Razgallah Rabie , walha Adel , Grissa Mohamed Habib , Beltaief Kaouthar , Mezgar Zied , Coubantini Ahmed , Bouida Wahid , Msolli Mohamed Amine , Boukef Riadh , Boubaker Hamdi , Nouira Semir 
Published: November 2021

Abstract
BackgroundLittle is known about the pattern and appropriateness of antibiotic prescriptions in patients with acute respiratory tract infections (ARTIs).Objective Describe the antibiotics used to treat ARTIs in Tunisian primary care offices and emergency departments (EDs), and assess the appropriateness of their use.MethodsIt was a multicenter cross-sectional observational clinical study conducted at 63 primary care offices and 6 EDS during a period of 8 months. Appropriateness of antibiotic prescription was evaluated by trained physicians using the medication appropriateness index (MAI). The MAI ratings generated a weighted score of 0 to 18 with higher scores indicating low appropriateness. The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the Ethics committee of Monastir Medical Faculty.ResultsFrom the 12880 patients screened we included 9886 patients. The mean age was 47.4, and 55.4% were men. The most frequent diagnosis of ARTI was were acute bronchitis (45.3%), COPD exacerbation (16.3%), tonsillitis (14.6%), rhinopharyngitis (12.2%) and sinusitis (11.5%). The most prescribed classes of antibiotics were penicillins (58.3%), fluoroquinolones (17.6%), and macrolides (16.9%). Antibiotic therapy was inappropriate in 75.5% of patients of whom 65.2% had bronchitis. 65% of patients had one or more antibiotic prescribing inappropriateness criteria as assessed by the MAI. The most frequently rated criteria were with expensiveness (75.8%) and indication (40%). Amoxicillin-clavulanic acid and levofloxacin were the most inappropriately prescribed antibiotics. History of cardiac ischemia ([OR] 3.66; 95% [CI] 2.17-10.26; p<0.001), asthma ([OR] 3.29, 95% [CI] 1.77-6.13; p<0.001), diabetes ([OR] 2.09, 95% [CI] 1.54-2.97; p=0.003), history of COPD ([OR] 1.75, 95% [CI] 1.43-2.15; p<0.001) and age >65 years (Odds Ratio [OR] 1.35, 95% confidence interval [CI] 1.16-1.58; p<0.001) were associated with a higher likelihood of inappropriate prescribing.ConclusionOur findings indicate a high inappropriate use of antibiotics in ARTIs treated in in primary care and EDs. This was mostly related to antibiotic prescription in acute bronchitis and overuse of expensive broad spectrum antibiotics. Future interventions to improve antibiotic prescribing in primary care and EDs is needed.Trial registrationthe trial is registered at Clinicaltrials.gov registry (NCT04482231)
Association Between Annual Change in FEV1 and Comorbidities or Impulse Oscillometry in Chronic Obstructive Pulmonary Disease.
Authors: Sugawara Hiroyuki , Saito Atsushi , Yokoyama Saori , Tsunematsu Kazunori , Chiba Hirofumi 
Published: November 2021

Abstract
Background:Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The decline in forced expiratory volume in one second (FEV1) is considered to be one of the most important outcome measures for evaluating disease progression. However, the only intervention proven to improve COPD prognosis is smoking cessation. This study therefore investigated the factors associated with annual FEV1 decline in COPD.Methods:This retrospective study followed up 65 patients treated for COPD for 5 years: 13 current smokers and 52 former smokers, 25 with pneumonia, 24 with asthma, 18 with cancer, and 17 with cardiovascular disease. The patients were divided into groups based on clinical cut-off parameters of the impulse oscillometry system (IOS): 11 high and 54 low R5, 8 high and 57 low R20, 21 high and 44 low R5–R20, 26 high and 39 low X5, 38 high and 27 low Fres, and 36 high and 29 low AX. We investigated whether the decline in FEV1 was associated with comorbidities and IOS parameters.Results:The annual change in FEV1 over 5 years was significantly affected by smoking status (current −66.2 mL/year vs former −5.7 mL/year, p < 0.01), pneumonia (with −31.5 mL/year vs without −8.9 mL/year, p < 0.05), asthma (with −30.2 mL/year vs −10.8 mL/year, p < 0.01), but not by cancer and cardiovascular disease. In the groups defined by IOS results, only the high AX group had significantly more annual decline in FEV1 and %FEV1 than the low AX group (−22.1 vs −12.8, p < 0.05 and −0.20 vs 0.40, p < 0.05, respectively).Conclusions:Smoking cessation, prevention of pneumonia, and asthma control could reduce FEV1 decline in COPD. AX might be a suitable parameter to predict the prognosis of COPD patients.
Interactions Between Remimazolam and Propofol in Combination With Sufentanil for Anesthesia During Gastroscopy
Authors: Lyu Song , Deng Qingchun , Lin Weixin , Wu Xiaofang 
Published: November 2021

Abstract
Background

This study was conducted to determine how remimazolam and propofol interact when given with sufentanil.
Methods

In this single-arm study, patients were assigned to one of five groups. The sample size was not determined in advance. When the median effective dose(ED50) and 95% confidence intervals were calculated, participants were stopped. The study included 159 patients who were scheduled for a gastrointestinal endoscopic examination and had an American Society of Anesthesiologists physical status of I/II. Patients were intravenously administered sufentanil (0.1 µg/kg), along with different doses of remimazolam and propofol depending on the group to which they were assigned. The endpoint for an effective response was the disappearance of the bilateral eyelash reflex. The up-and-down method was used to determine the ED50 within each treatment group. The ED50 deviations from the additive line were analyzed using isoradiometric analysis. The interaction coefficients were calculated by algebraic analysis. Interval estimation is used in statistical inference.
Results

In combination with sufentanil, the ED50 of remimazolam and propofol was determined to be 0.065 (0.057-0.074) mg/kg and 0.657 (0.590-0.724) mg/kg, respectively. After sufentanil administered, when 0.25, 0.5, and 0.75 ED50 remimazolam were given in combination with propofol, the interaction coefficients were 1.03,1.2and 1.08, respectively.
Conclusions

The dose of propofol with remimazolam may need to be reduced regardless of the additive or synergistic effect. There was a strong synergistic effect when the dose ratio of the two drugs was about 6:1 in mg/kg.
Trial registration:

The project was retrospectively registered on October 26, 2021 in Chinese clinical trial center with the registration number of ChiCTR2100052425.
Albumin and CRP, Which is the Best Biomarker for Postoperative Complications on Colorectal Surgery? Prospective Cohort Study
Authors: Cunha Miguel Fernandes , Mendes Beatriz , Mendanha Pedro , Miguel Ines , Rachadell Juan , Amorim Edgar , Castelo-Branco Pedro 
Published: November 2021

Abstract
Aim Our purpose was to investigate the potential role of albumin variation in comparison to C-reactive protein (CRP) variation as a predictive marker for postoperative complications in colorectal surgery. Methods An prospective cohort study was conducted. Adult patients who underwent elective colorectal surgery between January 2019 and December 2020 were eligible. Serum levels of albumin and CRP were measured preoperatively and on the first 4 postoperative days. Univariate analysis were performed to assess the association of albumin (Alb) and CRP with postoperative complications. Serum albumin variation (ΔAlb) and CRP variation (ΔCRP) were calculated. Receiver operating characteristic curve analysis and the Youden test were used to determine acuity and predictive cut-off values. Results Ninety-three patients were included. A CRP cut-off of 83.4 mg/dL on postoperative day (POD) 4 was the best predictor of postoperative global complications (p<0.001; AUC 0.83, 70% sensitivity, 91% specificity). Major complications were best correlated with ΔAlb on POD 2, 3 and 4 (p<0.001), with a ΔAlb cut-off of 27.4% on POD 2 showing the strongest association with this outcome (AUC 0.834, 83% sensitivity, 90% specificity). Regarding anastomotic leak, CRP on POD 3 showed better predictive values (p=0.037; AUC 0.792) with a cut-off value of 88.7 mg/dL (100% sensitivity, 52% specificity). Discussion Herein, the authors demonstrate there is a role for albumin variation, as an earlier and sensitive marker, to predict major postoperative complications in colorectal surgery. This analysis may be further applied to aid in the early identification of significant causes of re-operation and long-term morbimortality.