bluuebunny/crossref_metadata_2025_split huggingface dataset:
No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer’s disease and related dementia: results from the Drug Repurposing for Effective Alzheimer’s Medicines study
Authors: Desai Rishi J , Mahesri Mufaddal , Lee Su Been , Varma Vijay R , Loeffler Tina , Schilcher Irene , Gerhard Tobias , Segal Jodi B , Ritchey Mary E , Horton Daniel B , Kim Seoyoung C , Schneeweiss Sebastian , Thambisetty Madhav 
Published: October 2022

Abstract
We evaluated the hypothesis that phosphodiesterase-5 inhibitors, including sildenafil and tadalafil, may be associated with reduced incidence of Alzheimer’s disease and related dementia using a patient-level cohort study of Medicare claims and cell culture-based phenotypic assays. We compared incidence of Alzheimer’s disease and related dementia after phosphodiesterase-5 inhibitor initiation versus endothelin receptor antagonist initiation among patients with pulmonary hypertension after controlling for 76 confounding variables through propensity score matching. Across four separate analytic approaches designed to address specific types of biases including informative censoring, reverse causality, and outcome misclassification, we observed no evidence for a reduced risk of Alzheimer’s disease and related dementia with phosphodiesterase-5 inhibitors;hazard ratio (95% confidence interval): 0.99 (0.69–1.43), 1.00 (0.71–1.42), 0.67 (0.43–1.06), and 1.15 (0.57–2.34). We also did not observe evidence that sildenafil ameliorated molecular abnormalities relevant to Alzheimer’s disease in most cell culture-based phenotypic assays. These results do not provide support to the hypothesis that phosphodiesterase-5 inhibitors are promising repurposing candidates for Alzheimer’s disease and related dementia.
A Qualitative Scoping Review of Early-Terminated Clinical Trials Sponsored by the Department of Veterans Affairs Cooperative Studies Program From 2010 to 2020
Authors: Goldberg Alexa , Bakhireva Ludmila N , Page Kimberly , Henrie Adam M 
Published: October 2022

Abstract
Increasing attention has been paid to the risks and benefits of terminating large clinical trials before reaching prespecified targets, because such decisions can greatly affect the implementation of findings. The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) is a research infrastructure dedicated to conducting high-quality clinical research. A scoping review was performed to characterize barriers preventing the attainment of prespecified recruitment, statistical power, or sample-size targets in VA CSP trials. A trial was eligible for inclusion if the trial was sponsored by the VA CSP, primary findings were published within the last 10 years, and a decision was made to terminate enrollment or follow-up before meeting a priori recruitment or endpoint targets. In 11 of 29 included trials (37.9%), a decision was made to terminate the trial early. The most common reason for early termination was related to under-recruitment (n = 5). Other reasons included early detection of safety signals (n = 2), futility (n = 1), and benefit (n = 1). This review highlights recruitment as a critical facet of trial conduct that may hinder the production of high-quality data and thus warrant additional attention. Solutions to enhance recruitment now implemented by the VA CSP, including dedicated enrollment infrastructure and screening facilitated by informatics approaches, show promise in reducing this cause for early termination.
Erectile Function, Sexual Satisfaction, and Cognitive Decline in Men From Midlife to Older Adulthood
Authors: Slayday Riki E , Bell Tyler R , Lyons Michael J , Warren , BA Teresa S , Toomey Rosemary , Vandiver Richard , Sliwinski Martin J , Kremen William S , Franz Carol E 
Published: October 2022

AbstractBackground and ObjectivesVascular theories of cognitive aging have focused on macrovascular changes and cognitive decline. However, according to the artery-size hypothesis, microvascular changes, such as those that underlie changes in erectile function, may also play an important role in contributing to cognitive decline. Thus, we examined associations between erectile function, sexual satisfaction, and cognition starting in middle age because this represents a transition period where declines in these areas emerge.Research Design and MethodsWe examined 818 men from the Vietnam Era Twin Study of Aging across three waves at mean ages 56, 61, and 68. Erectile function and sexual satisfaction were measured using the International Index of Erectile Function. Cognitive performance was measured using factor scores for episodic memory, executive function, and processing speed. We tested multilevel models hierarchically, adjusting for demographics, frequency of sexual activity, and physical and mental health confounders to examine how changes in erectile function and sexual satisfaction related to changes in cognitive performance.ResultsLower erectile function at baseline was related to poorer performance in all cognitive domains at baseline and faster declines in processing speed over time. However, baseline sexual satisfaction was unrelated to cognitive performance. Decreases in erectile function and sexual satisfaction were both associated with memory decline.Discussion and ImplicationsDecreasing sexual health may signal an increased risk for cognitive decline. We discuss potential mechanisms, including microvascular changes and psychological distress. Discussing and tracking sexual health in middle-aged men may help to identify those likely to face memory decline.
The transmission of ‘The West Saxon Royal Genealogy’: a phylogenetic approach
Authors: Sparks Nicholas A , Windram Heather F , Howe Christopher J 
Published: October 2022

Abstract
We present a case study in the application of phylogenetic and other computational analyses to an Old English textual tradition. We chose the West Saxon royal genealogy for investigation because there are interesting problems in ascertaining the transmission of the text. We present a concise, up-to-date account of the manuscript tradition, a summary of the scholarly literature including current debates, and discuss phylogenetic and other analyses used to explore the tradition. We show how the results from phylogenetic analysis are consistent with interpretations advanced by scholars based on traditional methods of textual criticism. We also suggest a new textual grouping not mentioned before in the literature, and thus offer a new insight into this tradition. The suggested textual relationship finds support on historical and palaeographical grounds, and on that basis, we postulate the existence of a lost eleventh-century exemplar from Canterbury. The value of this article therefore lies in two main directions: first, we demonstrate the value of employing a combination of phylogenetic and other computer-based analysis methods with an Old English tradition; and second, we offer a striking new insight into the transmission and textual history of an important medieval English text.
Southern American Evangelicalism
Authors: Smith Samuel C. 
Published: October 2022

Abstract
This chapter argues that a vibrant, multidenominational evangelical presence emerged in the colonial South long before the First Great Awakening, setting the stage for its early expansion and long-lasting entrenchment in the region. Evangelical dissenters in the Carolina and Georgia lowcountry settled simultaneously with Anglican establishment, making it possible to extract enough concessions early on to expand their influence throughout and beyond the colonial era. The southern backcountry regions afforded even greater freedoms from some of the more intrusive inroads of authority. While tidewater Virginia’s establishment allowed minimal religious dissent, revivalism’s impressive growth in the mid-eighteenth century, even among some Anglicans, forced previously unattainable levels of recognition for evangelicals. This give-and-take tension would eventually help make Virginia the center of political negotiations for religious liberty. Overall, the colonial South was a seed bed of primitive space in the context of controlled opposition, a reality that fostered a deeply entrenched and still-dominant evangelical presence.
Poetry
Authors: Roberts Wendy Raphael 
Published: October 2022

Abstract
This chapter argues that early evangelicalism cannot be properly understood apart from its poetry and urges scholars to more thoroughly and carefully integrate revival verse into evangelical historiography and literary history. The author claims that early evangelicalism should be understood as an aesthetic movement integral to the aesthetic shifts and literary cultures of the transatlantic eighteenth century. Through one brief test case, Ralph Erskine’s bestselling poem Gospel Sonnets and two women poets who directly responded to it, Sarah Moorhead and Phillis Wheatley Peters, the chapter shows that attending to evangelicalism’s deep investment in aesthetics and poetic form has direct implications for understanding race, class, and gender in early evangelical culture.
George Whitefield and New Birth Preaching
Authors: Schlenther Boyd Stanley 
Published: October 2022

Abstract
As an antidote to the supine faith that they believed had infected British Christianity, early Methodists framed their message around the concept of a “New Birth.” Its most vibrant version was manifest in the proclamations of the eighteenth-century’s most famous Anglophone preacher, George Whitefield. The three decades of his public ministry added a cutting edge to the Christian message, which both sharpened an appeal for individuals’ radical inward conversion and contributed a serious challenge to traditional patterns of ecclesiastical practice. In the process, Whitefield drifted from his Anglican moorings, clearly revealed by his open castigation of a number of Church of England clerics, including bishops. Although participating extensively in utilizing the printing press to disseminate his sermons and other writings, it is clear that his message was most effectively conveyed through his robust and notably dramatic preaching. Moreover, his arresting use of literary devices, such as metaphor and simile, together with homely anecdotes, made Whitefield’s public proclamations highly attractive, a dramatic demonstration of his central new-birth message. However, following his death, in Whitefield’s absence evangelical Christianity began to adopt a perhaps more balanced appeal to a Christian’s, and Christianity’s, life and work.
Capitalism
Authors: Laborie Lionel 
Published: October 2022

Abstract
This chapter explores the spread of evangelicalism in continental Europe and the British Empire against the backdrop of the rise of capitalism in the eighteenth century. Starting from the revocation of the Edict of Nantes in 1685, it briefly surveys different attitudes to religious tolerance across northern Europe to highlight the often-overlooked contribution of Huguenot, millenarian, and commercial networks to the emergence of evangelicalism. All of these groups either influenced early evangelicals theologically or supported their missions logistically and financially. Accordingly, this chapter surveys the economic foundations and teachings of Halle Pietists, the Moravians, and Methodists, as well as how their religious discourses evolved over the eighteenth century to adapt to the rise of capitalism. Overall it is argued that, although early evangelicals shared millenarian beliefs and experimented communal lifestyles, they rapidly reinvented themselves to become economically and theologically competitive on the religious marketplace. The support of wealthy bankers and merchants proved essential in this process and suggests that eighteenth-century capitalists helped finance early evangelicalism.
German Pietism
Authors: Stievermann Jan 
Published: October 2022

Abstract
This chapter surveys, by way of important examples, the great plurality of German Pietism in various territories of the Holy Roman Empire and abroad, from the last third of the seventeenth to the last third of the eighteenth centuries. The focus is on the manifold relations between these different branches of Pietism and “awakened” individuals, movements, and undertakings associated with early evangelicalism in Britain and its colonies. Such relations came about either through migration, co-operations, or the cultivation of networks of correspondence and print exchange. Examples include theologians, reformers, groups, and projects connected with both Reformed and Lutheran state churches, such as the émigré pastor Theodorus Jacobus Frelinghuysen, who was directly involved in the Great Awakening, or the reception of Gerhard Tersteegen by German Pietists in the colonies but also the Wesley brothers. Special attention is paid to Halle Pietism and the Francke Foundation that had close ties with numerous reform and revival movements across the British Empire and (also by sending Heinrich Melchior Mühlenberg) played a key role in the organization of American Lutheranism. Among the examples of radical Pietism examined in this chapter are Labadism and the Pietist Baptist groups that sought refuge in Pennsylvania and founded the Ephrata community. The chapter concludes by turning to the question of how, given these many entanglements, German Pietists and their Anglophone brethren viewed each other and interpreted their religious identities.
Chemical Triggering Cyanobacterial Glycogen Accumulation: Methyl Viologen Treatment Increases Synechocystis sp. PCC 6803 Glycogen Storage by Enhancing Levels of Gene Transcript and Substrates in Glycogen Synthesis
Authors: Sukkasam Nannaphat , Leksingto Jidapa , Incharoensakdi Aran , Monshupanee Tanakarn 
Published: October 2022

Abstract
Two-stage cultivation is effective for glycogen production by cyanobacteria. Cells were first grown under adequate nitrate supply (BG11) to increase biomass and subsequently transferred to nitrogen deprivation (–N) to stimulate glycogen accumulation. However, the two-stage method is time-consuming and requires extensive energy. Thus, one-stage cultivation that enables both cell growth and glycogen accumulation is advantageous. Such one-stage method could be achieved using a chemical triggering glycogen storage. However, there is a limited study on such chemicals. Here, nine compounds previously reported to affect cyanobacterial cellular functions were examined in Synechocystis sp. PCC 6803. 2-Phenylethanol, phenoxyethanol, 3-(3,4-dichlorophenyl)-1,1-dimethylurea and methyl viologen can stimulate glycogen accumulation. The oxidative stress agent, methyl viologen significantly increased glycogen levels up to 57% and 69% [w/w dry weight (DW)] under BG11 and –N cultivation, respectively. One-stage cultivation where methyl viologen was directly added to the pre-grown culture enhanced glycogen storage to 53% (w/w DW), compared to the 10% (w/w DW) glycogen level of the control cells without methyl viologen. Methyl viologen treatment reduced the contents of total proteins (including phycobiliproteins) but caused increased transcript levels of glycogen synthetic genes and elevated levels of metabolite substrates for glycogen synthesis. Metabolomic results suggested that upon methyl viologen treatment, proteins degraded to amino acids, some of which could be used as a carbon source for glycogen synthesis. Results of oxygen evolution and metabolomic analysis suggested that photosynthesis and carbon fixation were not completely inhibited upon methyl viologen treatment, and these two processes may partially generate upstream metabolites required for glycogen synthesis.
Models for Apothecial Emergence and Ascospore Discharge of Monilinia vaccinii-corymbosi in Michigan Blueberry Fields
Authors: Neugebauer Kerri A. , Dabbah Gina M. , Miles Timothy D. 
Published: October 2022

Monilinia vaccinii-corymbosi ( Mvc) is the causal agent of mummy berry in highbush blueberries. The primary inoculum of Mvc consists of ascospores that are discharged from apothecia on overwintered mummified blueberry fruits on the ground below blueberry bushes. Models currently exist in southern climates to predict the emergence of apothecia and ascospore discharge based on growing degree days. To better understand the release of primary inoculum in northern climates, apothecial emergence and ascospore discharge were studied in relation to weather variables. A Burkard spore trap was used to collect ascospores in blueberry fields with a history of the disease in 2002, 2003, 2004, and 2009. Peak ascospore discharge was inversely correlated with daily relative humidity, and the majority of ascospores were initially discharged between 61 and 291 growing degree days (using 5.5°C base) and after 1,549 to 1,924 chill hours (above freezing) were attained. The chilling requirement of pseudosclerotia was studied by removing them at different times during the winter and allowing them to germinate in the laboratory. Additionally, the optimal average apothecial cup diameter in the field was investigated in relation to ascospore discharge (between 3 and 7 mm). Finally, we proposed a simplified degree-day model to predict apothecia emergence and ascospore discharge with apothecia emergence timings at several locations from 2007 to 2010. This information can be used to predict mummy berry apothecium emergence and ascospore discharge and could be incorporated into web-based risk modeling applications for providing growers with useful tools to improve fungicide spray timing.
Efficacy and safety of high-dose esomeprazole–amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial
Authors: Bi Hanxin , Chen Xingxing , Chen Yuxin , Zhao Xin , Wang Shasha , Wang Jiehong , Lyu Ting , Han Shuang , Lin Tao , Li Mingquan , Yuan Donghong , Liu Junye , Shi Yongquan 
Published: October 2022

Abstract

Background:
High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.

Methods:
This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.

Results:
A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P
< 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.

Conclusions:
Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.

Trial registration:
Clinicaltrials.gov, NCT04678492.
Intestinal homeostasis in autoimmune liver diseases
Authors: Liu Qiaoyan , He Wei , Tang Ruqi , Ma Xiong 
Published: October 2022

Abstract
Intestinal homeostasis depends on complex interactions between the gut microbiota and host immune system. Emerging evidence indicates that the intestinal microbiota is a key player in autoimmune liver disease (AILD). Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis have been linked to gut dysbiosis. Diverse mechanisms contribute to disturbances in intestinal homeostasis in AILD. Bacterial translocation and molecular mimicry can lead to hepatic inflammation and immune activation. Additionally, the gut and liver are continuously exposed to microbial metabolic products, mediating variable effects on liver immune pathologies. Importantly, microbiota-specific or associated immune responses, either hepatic or systemic, are abnormal in AILD. Comprehensive knowledge about host-microbiota interactions, included but not limited to this review, facilitates novel clinical practice from a microbiome-based perspective. However, many challenges and controversies remain in the microbiota field of AILD, and there is an urgent need for future investigations.
FLACS vs conventional phacoemulsification by junior cataract surgeons: randomized trial
Authors: Vasavada Abhay R. , Vasavada Shail A. , Nath Vandana , Vasavada Vaishali , Patel Priyanka 
Published: October 2022

Purpose:
To report intraoperative performance and postoperative outcomes of femtosecond laser–assisted cataract surgery (FLACS) and conventional phacoemulsification (PE) in the hands of junior surgeons.

Setting:
Iladevi Cataract & IOL Research Centre, Ahmedabad, Gujarat, India.

Design:
Prospective single-masked randomized controlled trial.

Methods:
320 eyes (320 patients) undergoing cataract surgery for uneventful cataracts in the hands of junior surgeons were randomized to Group 1—FLACS or Group 2—PE. Intraoperatively, cumulative dissipated energy (CDE) and fluid used were compared. Postoperatively, the following were compared: central corneal thickness (CCT) on day 1, 1 week, and 1 month; corneal clarity (day 1 and 1 week); anterior chamber inflammation (day 1 and 1 week); change in endothelial cell density (ECD) at 6 months postoperatively; and corrected distance visual acuity (CDVA) at 1 week and 1 month postoperatively.

Results:
157 and 158 patients in groups 1 and 2 analysed. Intraoperatively, CDE (5.41 ± 2.73 vs 8.83 ± 4.28 in Groups 1 and 2, P = .0001) and fluid used (79.33 ± 33.46 vs 101.82 ± 32.23 mL in Groups 1 and 2, P < .0001) were significantly lesser in Group 1. CCT was significantly higher in Group 2 on day 1 (550.96 ± 33.64 vs 587.70 ± 55.76 μm in Groups 1 and 2, P < .0001) and at 1 week postoperatively (527.94 ± 30.78 vs 545.11 ± 35.17 μm in Groups 1 and 2, P = .001). 72% of eyes had clear corneas on day 1 in Group 1 compared with 39% in Group 2 (P = .01). Anterior chamber inflammation and CDVA were comparable. Change in ECD was significantly lower (9.3%) in Group 1 vs 12.7% in Group 2, P < .0001.

Conclusions:
FLACS showed lower intraoperative CDE, fluid usage, lesser increase in CCT, better early postoperative corneal clarity, and lesser change in ECD at 6 months postoperatively in the hands of junior surgeons during standard cataract surgery.