bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and mortality risk of older adults with non‐small cell cancer in Taiwan: A population‐based cohort study
Authors: Wang Chun‐Chieh , Chiu Shao‐Wen , Wu Shang‐Jung , Pan Lung‐Kwang , Yen Yung‐Feng , Lai Yun‐Ju , Chen Chu‐Chieh 
Published: August 2023

AbstractBackgroundOlder patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non‐small cell cancer (NSCLC) in Taiwan.MethodsThis study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan–Meier survival curves were drawn.ResultsA total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan–Meier survival curves showed significant differences across the three treatment options (log‐rank p < 0.001). Results from multivariate Cox regression demonstrated that patients on palliative treatment (adjusted HR: 0.52, 95% CI: 0.48–0.56, p < 0.001) and curative treatment (adjusted HR: 0.45, 95% CI: 0.42–0.48, p < 0.001) had a significantly lower mortality risk than those with no treatment. The subgroup analyses stratified by cancer stages also showed consistent findings.ConclusionElderly patients with NSCLC had significantly decreased mortality risk when receiving curative or palliative treatment compared with those without treatment. In the future, further studies are warranted to investigate complications and quality of life of elderly patients with NSCLC during palliative or curative treatment.
Medication treatment for alcohol use disorder in special populations
Authors: Malhotra Aniket , Drexler Karen , Hsu Michael , Tang Yi‐lang 
Published: August 2023

AbstractBackground and ObjectivesAlcohol use disorder (AUD) is a significant public health concern, with underutilized effective treatments, particularly in special populations. This article summarizes the current evidence and guidelines for treating AUD in special populations.MethodsThis article is a literature review that synthesizes the latest research on AUD treatment for special populations. We screened 242 articles and included 57 in our final review.ResultsThere are four food and Drug Administration‐approved medications for AUD (MAUD): disulfiram, oral naltrexone, extended‐release injectable naltrexone (XR‐NTX), and acamprosate. Naltrexone and disulfiram have the potential to cause liver toxicity, and acamprosate should be avoided in patients with severe kidney disease. Psychosocial treatments should be considered first‐line for pregnant and nursing patients. Naltrexone is contraindicated in patients on opioids, as it may precipitate acute withdrawal. For patients experiencing homelessness, nonabstinent treatment goals may be more practical, and XR‐NTX should be considered to improve adherence. Limited evidence suggests medication can improve AUD treatment outcomes in adolescents and young adults. For patients with poor treatment response despite adequate medication adherence, switching to a different medication and augmentation with psychosocial treatments should be considered.Discussion and ConclusionsUnderstanding the unique considerations for special populations with AUD is crucial, and addressing their special needs may improve their treatment outcomes.Scientific SignificanceOur study significantly contributes to the existing literature by summarizing crucial information for the treatment of AUD in special populations, highlighting distinct challenges, and emphasizing tailored approaches to improve overall health and well‐being.
Estimating habit‐forming and variety‐seeking behavior: Valuation of recreational birdwatching
Authors: Guilfoos Todd , Thomas Priya , Kolstoe Sonja 
Published: August 2023

AbstractPast experiences influence choices, and people's preferences for more similar (habit‐forming) or different (variety‐seeking) experiences are reflected in these choices. We develop a structural estimation framework to capture whether people are habit forming or variety seeking and apply it to the choice of recreation site. This research contributes to the revealed preference literature by demonstrating how to account for habit or variety‐seeking behavior in recreation site choice models in a two‐stage framework. Using this framework, we estimate similarity weights that reflect the birders habit formation and variety seeking preferences. Predicted probabilities from the first stage model are then incorporated into the second stage, a mixed logit recreation site choice model of bird watching trips from eBird, by their members. We find that including the dynamic elements of choice, specifically variety‐seeking behavior, can double the estimated willingness to pay (WTP) for individual sites relative to the static model. Although our sample of bird watching trips taken by eBird members is a sample of convenience, these results suggest that static models of recreation site choice are a lower bound on our recreation demand WTP estimates. We find variety‐seeking preferences are related to land cover and the site's fixed attributes, whereas habit formation appears for seasonality in the bird watching context.
CUB domains are not required for OVCH2 function in sperm maturation in the mouse epididymis
Authors: Kent Katarzyna , Nozawa Kaori , Sutton Courtney , Daniel Frey , Ikawa Masahito , Garcia Thomas X. , Matzuk Martin M. 
Published: August 2023

AbstractBackgroundOvochymase 2 (Ovch2) is an epididymis‐specific gene that is required for male fertility. While a multitude of reproductive tract‐specific genes required for male fertility have been identified, OVCH2 is thus far the first protein required for male fertility that contains Complement C1r/C1s, Uegf, Bmp1 (CUB) domains located in tandem in the C‐terminus of the protein. Identifying the functional significance of this unique domain has implications in better understanding fertility and infertility and as a potential contraceptive target.ObjectiveThe goals of these studies were to understand the influence and requirement of OVCH2 CUB domains in the localization and functional requirement of OVCH2 in sperm maturation and function.Materials and methodsTo this end, we performed in vivo localization analysis of OVCH2 and reproductive phenotype analysis of mice containing C‐terminal FLAG tag on OVCH2, with either the entire protein intact, or CUB2 or both CUB1 and CUB2 genetically ablated. All mice were generated through the CRISPR/Cas9 gene editing approach.ResultsWe found that OVCH2 is specifically expressed in the proximal caput epididymidis, and the absence of CUB2 did not affect this localization pattern. Although the absence of both CUB domains significantly reduced sperm motility and progressive motility, this effect was not manifested in a reduction in fertility over a 6‐month period mating trial, which showed no significant differences between control and CUB deletant mice. Further, the absence of one or both CUB domains did not affect reproductive organ structure or sperm morphology.ConclusionsOur studies demonstrate that the CUB domains are not required for fertility in male mice, at least under the normal animal housing conditions our mice were tested in, and suggest that the enzymatic activity of the OVCH2 protease, in the absence of its CUB domains, is sufficient for normal sperm processing in the epididymis. Although our findings do not preclude the possibility that OVCH2 CUB domains are required under a yet‐identified stress condition, our findings demonstrate that the most likely region for deleterious mutations in men with idiopathic infertility and the most vulnerable site for inhibition of OVCH2 protein function is in its protease domain, and not its CUB domains. Our findings have implications in the genetic screening of infertile men and the development of a novel non‐hormonal male contraceptive by honing in on the more critical region of a functionally required protein.
Iatrogenic bladder injury following gynecologic and obstetric surgery: A systematic review and meta‐analysis
Authors: Jensen Ann‐Sophie , Heinemeier Ina Isabell Kathleen , Schroll Jeppe Bennekou , Rudnicki Martin 
Published: August 2023

AbstractIntroductionIatrogenic bladder injury is a rare complication following obstetric and gynecologic surgery and only sparse information is available regarding length of transurethral catheterization following injuries, suturing techniques including choice of suture, and complications. The primary aim of this systematic review was to evaluate length of transurethral catheterization in relation to complications following iatrogenic bladder injury. Second, we aimed to evaluate the number of complications following repair of iatrogenic bladder injuries and to describe suture technique and best choice of suture.Material and methodsA systematic review and meta‐analysis was conducted, and the results were presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. PubMed, Embase, and Medline electronic databases were searched, and followed by screening from two independent reviewers. Studies published between January 2000 and March 2023 describing methods of bladder injury repair following obstetric or gynecologic benign surgery were included. Data extraction was done using Covidence. We performed a meta‐analysis on complications after repair and explored this with a meta‐regression analysis (Metafor package R) on length of catheterization to determine if length of catheterization influenced the risk of complication. A risk of bias tool from Cochrane was used to assess risk of bias and the study was registered in PROSPERO (CRD42021290586).ResultsOut of 2175 articles, we included 21 retrospective studies, four prospective studies, and one case‐control study. In total, 595 bladder injuries were included. Cesarean section was the most prominent surgery type, followed by laparoscopically assisted vaginal hysterectomy. We found no statistically significant association between length of transurethral catheterization and numbers of complications following repair of iatrogenic bladder injuries. More than 90% of injuries were recognized intraoperatively. Approximately 1% had complications following iatrogenic bladder injury repair (0.010, 95% confidence interval 0.0015–0.0189, 26 studies, 595 participants, I2 = 4%).ConclusionsOur review did not identify conclusive evidence on the length of postoperative catheterization following bladder injury warranting further research. However, the rate of complications was low following iatrogenic bladder injury with a wide range of repair approaches.
Visualization of contractions: Evaluation of a new experience design concept to enhance the childbirth experience
Authors: Thijssen Kirsten M. J. , Kierkels Jeanine J. M. , van Meurs Andrea , Verhoeven Corine J. , van der Hout‐van der Jagt M. Beatrijs , Oei S. Guid 
Published: August 2023

AbstractBackgroundThe purpose of this study was to develop and evaluate an innovative design proposition intended to help enhance the childbirth experience. The innovation consists of a smartphone application for birth preparation during pregnancy with information and coaching, in addition to a wall projection at the labor ward that visualizes the progress of labor based on uterine monitoring data.MethodsWe conducted a randomized controlled clinical pilot study. Singleton pregnant people pursuing a vaginal birth were recruited between 28 and 32 weeks of gestation and allocated to the intervention group (mobile application during the third trimester and wall projection at the labor ward) or to care as usual. Childbirth expectations and experiences were measured with validated questionnaires, which were completed at 32 and 36 weeks of gestation, immediately after birth, and at 4 weeks postpartum. Quantitative outcomes were analyzed and feedback about the proposition was evaluated using qualitative methods.ResultsThe qualitative feedback from patients was largely positive; however, we could not detect any significant differences between the intervention and control groups about fear of childbirth and other outcome measures.ConclusionIn this pilot study, we evaluated a new experience design proposition for pregnancy and childbirth. This study generated data that will help to further improve and evaluate similar innovations in the future. This application may facilitate participatory care, promoting active involvement of parents in the healthcare processes of pregnancy and childbirth.
Antibiotics versus non‐antibiotic treatments for acute otitis externa: A systematic review and meta‐analysis
Authors: Di Traglia Rosalind , Tudor‐Green Ben , Muzaffar Jameel , Borsetto Daniele , Smith Matthew E. 
Published: August 2023

AbstractBackgroundOtitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics.This systematic review and meta‐analysis of randomised controlled trials aims to assess the effectiveness of topical non‐antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa.MethodsSystematic review and meta‐analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non‐antibiotic agents in adults and children with acute otitis externa. Non‐antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non‐pharmaceuticals and astringents.ResultsSeventeen trials were eligible for inclusion, with 10 combined in meta‐analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta‐analysis.ConclusionAntiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.
Managing invasive hybrids with pond hydroperiod manipulation in an endangered salamander system
Authors: Cooper Robert D. , Shaffer H. Bradley 
Published: August 2023

AbstractWhen invasive and endangered native taxa hybridize, the resulting admixture introduces novel conservation challenges. Across a large region of central California, a hybrid swarm consisting of admixed endangered California tiger salamanders (CTS) (Ambystoma californiense) and introduced barred tiger salamanders (BTS) (Ambystoma mavortium) has replaced native populations, threatening the genetic integrity of CTS and the vernal pool systems they inhabit. We employed a large‐scale, genomically informed field experiment to test whether shortening breeding pond hydroperiod would favor native CTS genotypes. We constructed 14 large, seminatural ponds to evaluate the effect of hydroperiod duration on larval survival and mass at metamorphosis. We tracked changes in non‐native allele frequencies with a 5237‐gene exon capture array and employed a combination of custom Bayesian and generalized linear models to quantify the effect of pond duration on salamander fitness. Earlier work on this system showed hybrid superiority under many conditions and suggested that hybrids are favored in human‐modified ponds with artificially long hydroperiods. Consistent with these earlier studies, we found overwhelming evidence for hybrid superiority. Very short hydroperiods substantially reduced the mass (1.1–1.5 fold) and survival probability (10–13 fold) of both native and hybrid larvae, confirming that hydroperiod likely exerts a strong selective pressure in the wild. We identified 86 genes, representing 1.8% of 4723 screened loci, that significantly responded to this hydroperiod‐driven selection. In contrast to earlier work, under our more natural experimental conditions, native CTS survival and size at metamorphosis were always less than hybrids, suggesting that hydroperiod management alone will not shift selection to favor native larval genotypes. However, shortening pond hydroperiod may limit productivity of hybrid ponds, complementing other strategies to remove hybrids while maintaining vernal pool ecosystems. This study confirms and expands on previous work that highlights the importance of hydroperiod management to control invasive aquatic species.
A randomized, controlled single, and multiple ascending dose trial of the safety, pharmacokinetics and pharmacodynamics of SN1011 in healthy subjects
Authors: Zhu Leilei , Shi Rong , Zhao Tongfang , Ye Yujie , Tang Jie , Hu Yihui , Peng Peng , Wang Dong , Chong Clement , Xu Guolin , Leung Shui‐on , Yuan Wei’an 
Published: August 2023

AbstractThe purpose of this study was to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SN1011, a novel Bruton tyrosine kinase (BTK) inhibitor, and food effects in healthy subjects. In this phase I trial, subjects received single ascending doses (SADs) of SN1011 (100 to 800 mg), multiple ascending doses (MADs) of SN1011 (200 to 600 mg), or placebo q.d. Additionally, 12 subjects randomly received a single dose of SN1011 600 mg under fasting states and then fed states, vice versa. Safety was assessed per Common Terminology Criteria for Adverse Events version 5.0. Pharmacokinetic parameters were calculated by noncompartmental analysis and BTK receptor occupancy in peripheral blood monocytes was determined. Seventy‐one healthy subjects were dosed in five SAD cohorts, three MAD cohorts, and one food effect cohort, with 57 receiving SN1011 and 14 receiving placebo. No serious adverse events (AEs) were reported. There was no correlation between AE occurrences and SN1011 exposure. The three most frequent AEs with SN1011 were increased blood triglycerides, decreased neutrophil count, and decreased leucocyte count. SN1011 exhibited a dose‐proportional increase in maximum plasma concentration and area under the time concentration curve following single and multiple dose administrations, with an accumulation ratio of 1.5 to 2.2 after multiple dose administrations. No difference in SN1011 exposure was observed between fed states. BTK receptor occupancy remained above 83% over 24 h after single administration and remained above 80% for the MAD groups for 10 days of continuous q.d. administration. SN1011 was well‐tolerated and safe after single or multiple exposures to healthy subjects, supporting further clinical development of SN1011 for treatment of autoimmune diseases.
CYP2C19 loss‐of‐function alleles and use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel
Authors: Ramste Markus , Ritvos Markus , Häyrynen Sergei , Kiiski Johanna I. , Niemi Mikko , Sinisalo Juha 
Published: August 2023

AbstractOur aim was to investigate in a real‐life prospective patient cohort how CYP2C19 loss‐of‐function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants. The primary study outcome measurement was cardiovascular death or recurring myocardial infarction or stroke. Altogether, 608 patients (30.8%) carried CYP2C19 LOF alleles. During the 365‐day follow‐up 252 patients (12.8%) had an ischemic vascular event. Cardiovascular events were significantly more frequent in carriers of CYP2C19 LOF alleles (14.8%, 95% confidence interval [CI], 11.7–17.8) than in non‐carriers (10.8%, 95% CI, 9.0–12.6, p = 0.0159). Omeprazole or esomeprazole use was similar among LOF allele carriers (n = 131, 21.5%) and non‐carriers (n = 250, 18.3%, p = 0.185). Cardiovascular events were significantly more common in a composite group consisting of all CYP2C19 LOF carriers regardless of proton pump inhibitor use status and non‐carriers using omeprazole or esomeprazole than in non‐carriers not using omeprazole or esomeprazole (14.8%, 95% CI, 12.2–17.3 vs. 9.9%, 95% CI, 8.0–11.9, p = 0.00173). We observed significantly more cardiovascular events in carriers of CYP2C19 LOF variants and in non‐carriers using omeprazole or esomeprazole. For optimal patient care, both genetics and concomitant medication should be considered.
Coordinated monitoring and mergers and acquisitions
Authors: Croci Ettore , Mazur Mieszko , Salganik‐Shoshan Galla 
Published: August 2023

AbstractThis paper shows that coordinated monitoring by institutional investors affects how firms behave in the M&A market. We employ the spatial dimension of geographic links between major institutions as a proxy for interaction and information exchange—a process that determines the effectiveness of investor monitoring over firm management. Using data over the last 30 years, we show that the returns to acquiring shareholders are significantly higher, and M&A activity is significantly more intense when institutions coordinate better their monitoring efforts. Our results are robust to series of tests to gauge their sensitivity to different model specifications and estimation procedures.