bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of White Analytical Chemistry–Assisted Analytical Quality by Design Approach to Green Liquid Chromatographic Method for Concomitant Analysis of Anti-Hypertensive Drugs in Human Plasma
Authors: Prajapati Pintu , Shahi Abhinandan , Acharya Aneri , Pulusu Veera Shakar , Shah Shailesh 
Published: July 2023

Abstract
According to current concepts of white analytical chemistry (WAC), the use of organic solvents those are teratogenic and carcinogenic must be avoided for the protection of the environment and of the analysts. This led to the development and validation of the WAC–assisted green liquid chromatographic technique (reverse-phase high-pressure liquid chromatography (RP-HPLC)) for the simultaneous analysis of anti-hypertensive drugs (azilsartan medoxomil, chlorthalidone and cilnidipine) in human plasma and their fixed-dose combinations. The analytical quality by design approach was used in conjunction with the design of experiments and chemometrics concepts to develop the method. To develop the green RP-HPLC method, critical method variables (CMVs) and critical analytical attributes were identified using the multivariate analytical tools principal component analysis and partial least square regression. Using the Box–Behnken design, the design of experiments was used for CMV optimization and response surface analysis. It was possible to explore the analytical design space for the life cycle management of the RP-HPLC method. The developed method was found to be validated following International Council for Harmonization Q2 (R1) and M10 requirements. Using the red, green and blue paradigm, the existing and proposed chromatographic methods were evaluated for their validation efficacy, greenness profile and cost-effectiveness.
Leukopenia in autosomal dominant polycystic kidney disease: a single-center cohort of kidney transplant candidates with post-transplantation follow-up
Authors: Schellekens Pieter , Van Loon Elisabet , Coemans Maarten , Meyts Isabelle , Vennekens Rudi , Kuypers Dirk , Mekahli Djalila , Bammens Bert 
Published: July 2023

ABSTRACT

Background
Autosomal dominant polycystic kidney disease (ADPKD) has occasionally been associated with lower peripheral white blood cell (WBC) counts. This study aimed to investigate the peripheral blood cell counts in a large cohort of kidney transplant recipients before and after kidney transplantation and its potential impact on post-transplant outcomes.

Methods
This was a retrospective study with long-term follow-up data of 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals, of whom 392 had ADPKD.

Results
In total, 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals were included, of whom 392 had ADPKD. Both pre- and post-transplantation, ADPKD patients had significantly lower total WBC counts, and more specifically lower neutrophil, lymphocyte and eosinophil counts compared with the non-ADPKD patients. This observation was independent of potential confounders such as level of inflammation, smoking habit, vitamins and pre-transplant medication. Overall survival and kidney transplant survival were significantly better in ADPKD vs non-ADPKD transplant recipients and a longer time to first infection was observed. However, no association between blood cell counts and outcome differences was found.

Conclusions
In conclusion, this large single-center study reports a strong and independent association between ADPKD and lower peripheral WBC counts both before and after kidney transplantation. Considering the role of inflammation in disease progression, further investigation into the role of WBC in ADPKD is needed.
Women with PCOS have an increased risk for cardiovascular disease regardless of diagnostic criteria—a prospective population-based cohort study
Authors: Ollila Meri-Maija , Arffman Riikka K , Korhonen Elisa , Morin-Papunen Laure , Franks Stephen , Junttila Juhani , Piltonen Terhi T 
Published: July 2023

Abstract

Objective
Polycystic ovary syndrome (PCOS) is associated with many cardiovascular disease (CVD) risk factors, such as obesity, type 2 diabetes mellitus and hypertension. However, it remains debatable whether the presence of multiple CVD risk factors translates to increased CVD events.

Design
A prospective, population-based Northern Finland Birth Cohort 1966.

Methods
Individuals with an expected date of birth in 1966 in Northern Finland have been followed from birth. Women in the cohort were classified as having PCOS according to either the National Institute of Health (NIH) criteria (n = 144) or the Rotterdam criteria (n = 386) at age 31, and they were compared to women without any PCOS features. The study population was re-examined at age 46, and the incidence of major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke, heart failure and cardiovascular mortality, was recorded up to age 53.

Results
During the 22-year follow-up, both women with NIH-PCOS and women with Rotterdam-PCOS had a significantly higher risk for cardiovascular events than control women. The BMI-adjusted hazard ratio (HR) for MACE in the Rotterdam-PCOS group and the NIH-PCOS group was 2.33 (1.26-4.30) and 2.47 (1.18-5.17), respectively. The cumulative hazard curves in both diagnostic categories began to diverge at age 35. Regarding the individual CVD endpoints, MI was significantly more prevalent in both women with NIH-PCOS (P = .010) and women with Rotterdam-PCOS (P = .019), when compared to control women.

Conclusions
PCOS should be considered a significant risk factor for CVD. Future follow-up will show how the risk of CVD events develops after menopausal age.
Immunotherapies for the prevention and treatment of Staphylococcus aureus infections: updates and challenges
Authors: Chung Pooi Yin 
Published: July 2023

Abstract
Staphylococcus aureus is the leading cause of hospital-acquired infections and can cause a wide range of diseases from mild skin infections to invasive diseases including deep surgical site infections, life-threatening bacteremia, and sepsis. This pathogen remains a challenge to manage due to its ability to rapidly develop resistance to antibiotic treatment and to form biofilms. Despite the current infection control measures which involve mainly antibiotics, the burden of infection remains high. The ‘omics’ approaches have not led to the discovery of novel antibacterials at a pace sufficient to cope with the emergence of multidrug-resistant and biofilm-forming S. aureus, Hence, new strategies for anti-infective therapies need to be explored urgently. One promising strategy is harnessing the immune response to enhance the protective antimicrobial immunity in the host. This review discusses the potential of monoclonal antibodies and vaccines as alternatives to treat and manage infections caused by planktonic and biofilms of S. aureus.
Leveraging the genetic correlation between traits improves the detection of epistasis in genome-wide association studies
Authors: Stamp Julian , DenAdel Alan , Weinreich Daniel , Crawford Lorin 
Published: July 2023

Abstract
Epistasis, commonly defined as the interaction between genetic loci, is known to play an important role in the phenotypic variation of complex traits. As a result, many statistical methods have been developed to identify genetic variants that are involved in epistasis, and nearly all of these approaches carry out this task by focusing on analyzing one trait at a time. Previous studies have shown that jointly modeling multiple phenotypes can often dramatically increase statistical power for association mapping. In this study, we present the “multivariate MArginal ePIstasis Test” (mvMAPIT)—a multioutcome generalization of a recently proposed epistatic detection method which seeks to detect marginal epistasis or the combined pairwise interaction effects between a given variant and all other variants. By searching for marginal epistatic effects, one can identify genetic variants that are involved in epistasis without the need to identify the exact partners with which the variants interact—thus, potentially alleviating much of the statistical and computational burden associated with conventional explicit search-based methods. Our proposed mvMAPIT builds upon this strategy by taking advantage of correlation structure between traits to improve the identification of variants involved in epistasis. We formulate mvMAPIT as a multivariate linear mixed model and develop a multitrait variance component estimation algorithm for efficient parameter inference and P-value computation. Together with reasonable model approximations, our proposed approach is scalable to moderately sized genome-wide association studies. With simulations, we illustrate the benefits of mvMAPIT over univariate (or single-trait) epistatic mapping strategies. We also apply mvMAPIT framework to protein sequence data from two broadly neutralizing anti-influenza antibodies and approximately 2,000 heterogeneous stock of mice from the Wellcome Trust Centre for Human Genetics. The mvMAPIT R package can be downloaded at https://github.com/lcrawlab/mvMAPIT.
Multiple p38/JNK mitogen-activated protein kinase (MAPK) signaling pathways mediate salt chemotaxis learning in C. elegans
Authors: Huang Taoruo , Suzuki Kota , Kunitomo Hirofumi , Tomioka Masahiro , Iino Yuichi 
Published: July 2023

Abstract
Animals are able to adapt their behaviors to the environment. In order to achieve this, the nervous system plays integrative roles, such as perception of external signals, sensory processing, and behavioral regulations via various signal transduction pathways. Here genetic analyses of Caenorhabditis elegans (C. elegans) found that mutants of components of JNK and p38 mitogen-activated protein kinase (MAPK) signaling pathways, also known as stress-activated protein kinase (SAPK) signaling pathways, exhibit various types of defects in the learning of salt chemotaxis. C. elegans homologs of JNK MAPKKK and MAPKK, MLK-1 and MEK-1, respectively, are required for avoidance of salt concentrations experienced during starvation. In contrast, homologs of p38 MAPKKK and MAPKK, NSY-1 and SEK-1, respectively, are required for high-salt chemotaxis after conditioning. Genetic interaction analyses suggest that a JNK family MAPK, KGB-1, functions downstream of both signaling pathways to regulate salt chemotaxis learning. Furthermore, we found that the NSY-1/SEK-1 pathway functions in sensory neurons, ASH, ADF, and ASER, to regulate the learned high-salt chemotaxis. A neuropeptide, NLP-3, expressed in ASH, ADF, and ASER neurons, and a neuropeptide receptor, NPR-15, expressed in AIA interneurons that receive synaptic input from these sensory neurons, function in the same genetic pathway as NSY-1/SEK-1 signaling. These findings suggest that this MAPK pathway may affect neuropeptide signaling between sensory neurons and interneurons, thus promoting high-salt chemotaxis after conditioning.
Hypoxanthine Induces Signs of Bladder Aging With Voiding Dysfunction and Lower Urinary Tract Remodeling
Authors: Birder Lori A , Wolf-Johnston Amanda S , Zabbarova Irina , Ikeda Youko , Robertson Anne M , Cardozo Ricardo , Azari Fatemeh , Kanai Anthony J , Kuchel George A , Jackson Edwin K 
Published: July 2023

Abstract

Background
Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX–ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging.

Methods
Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg/kg/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed.

Results
HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence).

Conclusions
These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions.
The genesis of the PM-JAY health insurance scheme in India: technical and political elements influencing a national reform towards universal health coverage
Authors: Srivastava S , Bertone M P , Parmar D , Walsh C , De Allegri M 
Published: July 2023

Abstract
Many countries are using health insurance to advance progress towards universal health coverage (UHC). India launched the Pradhan Mantri Jan Arogya Yojana (PM-JAY) health insurance scheme in 2018. We examine the political economy context around PM-JAY policy formulation, by examining the perspectives of policy stakeholders shaping decisions around the reform. More specifically, we focus on early policy design at the central (national) level. We use a framework on the politics of UHC reform proposed by Fox and Reich (The politics of universal health coverage in low- and middle-income countries: A framework for evaluation and action. J. Health Polit. Policy Law 2015;40:1023–1060), to categorize the reform into phases and examine the interactions between actors, institutions, interests, ideas and ideology which shaped reform decisions. We interviewed 15 respondents in Delhi between February and April 2019, who were either closely associated with the reform process or subject experts. The ruling centre-right government introduced PM-JAY shortly before national elections, drawing upon policy legacies from prior and state insurance schemes. Empowered policy entrepreneurs within the government focused discourse around ideas of UHC and strategic purchasing, and engaged in institution building leading to the creation of the National Health Authority and State Health Agencies through policy directives, thereby expanding state infrastructural and institutional power for insurance implementation. Indian state inputs were incorporated in scheme design features like mode of implementation, benefit package and provider network, while features like the coverage amount, portability of benefits and branding strategy were more centrally driven. These balanced negotiations opened up political space for a cohesive, central narrative of the reform and facilitated adoption. Our analysis shows that the PM-JAY reform focused on bureaucratic rather than ideological elements and that technical compromises and adjustments accommodating the interests of states enabled the political success of policy formulation. Appreciating these politics, power and structural issues shaping PM-JAY institutional design will be important to understand how PM-JAY is implemented and how it advances UHC in India.
Bloc Politics at the UN: How Other States Behave When the United States and China–Russia Disagree
Authors: Nurullayev Dmitriy , Papa Mihaela 
Published: July 2023

Abstract
China and Russia have been progressively deepening their partnership in global governance to achieve common goals. However, do other states share their policy positions? Existing scholarship addresses the dyadic affinity among major powers and the growing importance of rising power groups, but it does not examine how the policy positions of other states align with those of the United States and its major rivals: China and Russia. To investigate how states align with the positions of these major powers, we examine voting patterns in the UN General Assembly over a 30-year period from 1991 to 2020. By utilizing simple t-tests and estimating both OLS and LOGIT models (N = 219,625), we find that the Sino–Russian positions enjoy much broader global support than those of the United States. Additionally, states that belong to the Group of 77 (G-77) and soft-balancing institutions such as the Shanghai Cooperation Organization and BRICS (Brazil, Russia, India, China, and South Africa) are more likely to align with China and Russia than states that do not belong to these groups. Conversely, members of NATO are more likely to side with the United States than their non-NATO counterparts. Further, the findings suggest that the effect of states’ membership in soft-balancing institutions on their propensity to align with China and Russia has steadily increased over time. Meanwhile, the effect of states’ membership in NATO on their likelihood to align with the United States lacks a clear temporal trajectory.
UCE phylogenomics, biogeography, and classification of long-horned bees (Hymenoptera: Apidae: Eucerini), with insights on using specimens with extremely degraded DNA
Authors: Freitas Felipe V , Branstetter Michael G , Franceschini-Santos Vinícius H , Dorchin Achik , Wright Karen W , López-Uribe Margarita M , Griswold Terry , Silveira Fernando A , Almeida Eduardo A B 
Published: July 2023

AbstractLong-horned bees (Apidae, Eucerini) are found in different biomes worldwide and include some important crop pollinators. In the Western Hemisphere, Eucerini received extensive taxonomic study during the twentieth century, resulting in several revisions of its genera. In contrast, progress on eucerine phylogenetic research and the genus-level classification has been slow, primarily due to the relatively homogeneous external morphology within the tribe and the rarity of many of its species in collections. Here, we present a comprehensive phylogenetic study of Eucerini based on ultraconserved elements, including 153 species from nearly all genera and subgenera and from all biogeographic regions where they occur. Many of these specimens are from museums and were collected as far back as 1909. We discuss the challenges of working with specimens with highly degraded DNA, present insights into improving phylogenetic results for both species-tree and concatenation approaches, and present a new pipeline for UCE curation (Curation of UltraconseRved Elements—CURE). Our results show the existence of seven main lineages in Eucerini and most of the genera and subgenera to be reciprocally monophyletic. Using a comprehensive and up-to-date phylogenetic framework, we: (1) propose taxonomic changes, including a new subtribal classification and reorganized generic and subgeneric limits; (2) estimate divergence times; and (3) conduct a detailed exploration of historical biogeography of long-horned bees. We find that eucerine lineages expanded their range onto most continents only after their initial diversification in southern South America during the Eocene.
Molnupiravir for the treatment of non-severe COVID-19: a systematic review and meta-analysis of 14 randomized trials with 34 570 patients
Authors: Sun Mingyao , Lai Honghao , Huang Jiajie , Liu Jianing , Li Ying , Tian Jinhui , Zhang Caiyun , Estill Janne , Zhang Zhigang , Ge Long 
Published: July 2023

Abstract

Background
Molnupiravir has been considered a promising candidate for COVID-19. Its efficacy and safety in non-severe COVID-19 patients and the differences between patients with different risk factors need further evaluation.

Methods
We conducted a systematic review and meta-analysis of randomized controlled trials that allocated adult patients with non-severe COVID-19 to molnupiravir or a control. We used random-effects models, and conducted subgroup analyses and meta-regression for COVID-19 patients with high-risk factors. The GRADE approach was used to rate the certainty of evidence.

Results
Fourteen trials with 34 570 patients were included. Moderate- to low-certainty evidence showed that molnupiravir was associated with a reduction in the risk of hospitalization (relative risk [RR] = 0.63, 95% CI: 0.47–0.85), risk of mechanical ventilation (RR = 0.37, 95% CI: 0.19–0.72) and time to symptom resolution (mean differences [MD] = −2.91 days, 95% CI: −3.66 to −2.16). However, no significant differences were found in adverse events, all-cause mortality, rate of and time to viral clearance, or duration of hospitalization. For the rate of viral clearance, subgroup effects were found between trials with low and high risk of bias (P = 0.001) and between trials with male or female majority (P &lt; 0.001). For admission to hospital, subgroup effects were also found between trials with ≥50% and &lt;50% of the participants being female (P = 0.04). Meta-regression showed a significant association between higher trial mean age and elevated risk of hospitalization (P = 0.011), and female majority and elevated risk of hospitalization (P = 0.011).

Conclusions
Molnupiravir was found to be effective in non-severe COVID-19, but the efficacy varied with age and sex.
Predicting emergency department visits and hospitalizations for patients with heart failure in home healthcare using a time series risk model
Authors: Chae Sena , Davoudi Anahita , Song Jiyoun , Evans Lauren , Hobensack Mollie , Bowles Kathryn H , McDonald Margaret V , Barrón Yolanda , Rossetti Sarah Collins , Cato Kenrick , Sridharan Sridevi , Topaz Maxim 
Published: July 2023

AbstractObjectivesLittle is known about proactive risk assessment concerning emergency department (ED) visits and hospitalizations in patients with heart failure (HF) who receive home healthcare (HHC) services. This study developed a time series risk model for predicting ED visits and hospitalizations in patients with HF using longitudinal electronic health record data. We also explored which data sources yield the best-performing models over various time windows.Materials and MethodsWe used data collected from 9362 patients from a large HHC agency. We iteratively developed risk models using both structured (eg, standard assessment tools, vital signs, visit characteristics) and unstructured data (eg, clinical notes). Seven specific sets of variables included: (1) the Outcome and Assessment Information Set, (2) vital signs, (3) visit characteristics, (4) rule-based natural language processing-derived variables, (5) term frequency-inverse document frequency variables, (6) Bio-Clinical Bidirectional Encoder Representations from Transformers variables, and (7) topic modeling. Risk models were developed for 18 time windows (1–15, 30, 45, and 60 days) before an ED visit or hospitalization. Risk prediction performances were compared using recall, precision, accuracy, F1, and area under the receiver operating curve (AUC).ResultsThe best-performing model was built using a combination of all 7 sets of variables and the time window of 4 days before an ED visit or hospitalization (AUC = 0.89 and F1 = 0.69).Discussion and ConclusionThis prediction model suggests that HHC clinicians can identify patients with HF at risk for visiting the ED or hospitalization within 4 days before the event, allowing for earlier targeted interventions.