bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of real-world evidence to assess health outcomes related to deprescribing medications in older adults: an International Society for Pharmacoepidemiology-endorsed systematic review of methodology
Authors: Hayes Kaleen N , Niznik Joshua David , Gnjidic Danijela , Moriarty Frank , Tran Nha , Coe Antoinette B , Zullo Andrew R , Zhang Sirui , Alcusky Matthew , Bennett Dimitri , Hartikainen Sirpa , Laroche Marie-Laure , Li Xiojuan , Lin Joshua K , Lund Jennifer L , Sessa Maurizio , Shmuel Shahar , Sirois Caroline , Talbot Denis , Tiihonen Miia , Wen Xuerong , Sawan Mouna J , Moga Daniela C 
Published: November 2024

Abstract
Background: Observational studies using real-world data (RWD) can address gaps in knowledge on deprescribing medications but are subject to methodological issues. Limited data exist on the methods employed to use RWD to measure the effects of deprescribing.
Objective: To describe methodological approaches used in observational studies of deprescribing medications in older adults.
Method: We conducted a systematic review in Medline for observational studies published in English (01/01/2000-09/14/2023) that examined the health effects of medication deprescribing in older adults. We described study characteristics and methods, focusing on the operationalization of deprescribing as an exposure and potential time-related biases.
Results: Forty-five studies were included, representing a variety of drug classes (e.g., statins, aspirin, bisphosphonates) and diseases. Most studies adequately addressed potential time-related biases. The definition of deprescribing was not clearly defined in 12 studies. There was heterogeneity regarding the minimum duration of time that qualified as deprescribing, even within a drug class; fewer than one-third of studies provided a justification for these definitions.
Conclusion: Observational studies are common to examine the effects of deprescribing; however, there were inconsistencies in measuring deprescribing and a lack of transparency in reporting. There is a need for minimum sufficient reporting criteria for observational studies on deprescribing.
Unveiling the True Price: Assessing the Economic Impact of Cosmetic Surgery Tourism on a Single Tertiary Center in Bahrain
Authors: Farhan Abeer , AlMahmeed Maryam , Fakhro Abdulla 
Published: November 2024

Abstract

Background
In light of the escalating cost of cosmetic surgery in Bahrain, the burgeoning “Cosmetic Surgery Tourism” sector has captured the attention of many Bahrainis. Neighboring countries aggressively promote affordable packages on numerous social media platforms, luring individuals with the allure of a vacation experience. However, insufficient postoperative care abroad has far-reaching implications that jeopardize both patient well-being and the integrity of the healthcare system.

Objectives
This study aims to assess the present patterns of complications related to cosmetic surgery tourism and the resulting financial burden on the Bahraini healthcare system.

Methods
A retrospective cost analysis and chart review were performed for all patients who presented with complaints associated with cosmetic surgeries between January 2018 and September 2023. After identifying patient demographics, procedure characteristics, admission data, length of stay, and intervention needs, a comprehensive cost analysis was conducted.

Results
A total of 30 patients manifested complications. The complications associated with abdominoplasty were the most prevalent. Iran emerged as the most frequented destination, with Egypt and Turkey following in order of prevalence. Surgical-site infections constituted the most common complications. Required interventions included admission for intravenous antibiotics, hyperbaric wound care, implant removal, and critical care admission. The projected expense to the hospital was 65,970 BHD (175,000 USD), equating to an average expenditure of 2200 BHD (5852 USD) per patient.

Conclusions
The allure of cost-effective cosmetic treatments often leads to complications that impose substantial economic burdens. The study concludes with policy recommendations to balance individuals’ freedom to seek healthcare abroad with long-term sustainability and equitable access to Bahrain's healthcare system.

Level of Evidence: 5 (Risk)
Sustained germination-promoting effect of cold atmospheric plasma on spinach seeds
Authors: Nishino Seiya , Shimizu Kaori , Horie Fuko , Fukuda Shizu , Izawa Shingo 
Published: October 2024

Abstract
Cold atmospheric plasma (CAP) irradiation exhibits a sterilizing effect without causing thermal denaturation or leaving behind residual toxicants. CAP also has potential applications in various fields, including agriculture, leading to research efforts in recent years. This study investigated the effects of CAP on the seed germination rate of spinach (Spinacia oleracea), which typically has a low seed germination rate. Our results confirmed that irradiation with N2-CAP and Air-CAP significantly enhanced the germination rate of spinach seeds. Notably, we discovered that CAP irradiation promoted germination even in spinach seeds coated with a fungicide (thiuram) and a disinfectant (Captan), which are commonly used. Additionally, we examined whether the interval between CAP irradiation and the subsequent germination-induction treatment influenced the germination efficiency. We found that the germination-promoting effect of CAP on spinach seeds persisted for at least 30 days, demonstrating the high utility and practicality of CAP in the agricultural sector.
Enhancing negative control selection: A comparative analysis of random and targeted sampling techniques for obtaining High-Quality RNA from normal breast tissue
Authors: Mehta Komal , Sharma Archana , Mehta Anurag , Tayal Juhi 
Published: November 2024

Abstract
Molecular profiling is a crucial aspect of cancer therapy selection, underscoring the necessity for representative sampling of both tumor and normal tissues. While much attention has been given to representative tumor sampling, there has been a notable lack of exploration into the issue of poor RNA quality in normal breast tissue processing. Normal breast tissue from the same patient is often used as a negative control for most “-omics” experiments. RNA extracted from normal breast tissues frequently contains nucleic acids from surrounding adipocytes, endothelial cells, and immune cells, leading to a low representation of ductal elements and skewed results. Therefore, ensuring a complete representation of breast glandular tissue is imperative. The study aimed to investigate the variations in RNA enrichment between a random sampling technique and a targeted sampling approach when visually selecting normal breast tissue sections as negative controls for “-omics” experiments. Fifteen female breast cancer subjects who underwent Modified Radical Mastectomy were selected for the study. Normal Breast tissue was visually examined, and samples were collected from random fat pockets (random sampling) and fibromuscular grey-white streak areas (targeted sampling). RNA was isolated, followed by spectrophotometric analysis, agarose gel electrophoresis and Agilent Tape station analysis. Histopathological assessments and a gene expression study for housekeeping genes were performed on both subsets. Tissues collected through targeted sampling exhibited significantly higher RNA quality than those obtained via random sampling. Histopathological analysis revealed cellular areas abundant in terminal ductular units within the targeted samples, and a final validation qPCR showed that the targeted samples were the most representative of normal breast glandular tissue. The comparative analysis of the two sampling methods clearly indicates that the targeted approach, with its superior accuracy and reliability, is the more practical choice for obtaining representative normal breast glandular tissue for “-omics” experiments.
Reported outcomes in studies of intermittent claudication - first step toward a core outcome set: systematic review
Authors: Shwan Akam , Lamidi Segun , Chan Calvin , Daniels Elizabeth , Song-Smith Charlie , Hanna Lydia , Sounderajah Viknesh , Houghton John S M , Sayers Rob D 
Published: November 2024

Abstract

Introduction
This review aimed to compile an exhaustive list of all outcome measures and identify different characteristics of the outcomes reported in studies of intermittent claudication as the first step in developing a core outcome set for intermittent claudication.

Method
Medline and Embase were searched for all studies including individuals with intermittent claudication and reporting ≥1 outcome from January 2015 to August 2024. Abstract, full text screening and data extraction were performed by two investigators independently. All reported outcome measures were extracted verbatim and categorized by Dodd’s domains (Core Outcome Measures in Effectiveness Trials registration: COMIC Study, 1590; https://www.comet-initiative.org/Studies/Details/1590).

Results
4985 studies were screened and 408 were included. A total of 541 unique outcomes across 25 Dodd’s domains were identified. Ankle–brachial pressure index was the most frequently reported outcome. Among the 541 unique outcomes, 386 outcomes were only reported once. Only 38.9% of the studies exclusively included patients with intermittent claudication. Patient-reported outcomes were reported in 36.2% of studies. There were wide variations in the definition of commonly used outcome measures (for example, major adverse limb event and primary patency) across different studies.

Conclusion
There is substantial heterogeneity in reported outcomes in studies of intermittent claudication. Most reported outcomes are clinical/physiology oriented rather than patient centred. Development of a core outcome set for intermittent claudication is vital to improve and standardize reporting in future research.
Lung development genes, adult lung function and cognitive traits
Authors: Talaei Mohammad , Waters Sheena , Portas Laura , Jacobs Benjamin M , Dodd James W , Marshall Charles R , Minelli Cosetta , Shaheen Seif O 
Published: November 2024

Abstract
Lower lung function is associated with lower cognitive function and an increased risk of dementia. This has not been adequately explained and may partly reflect shared developmental pathways. In UK Biobank participants of European ancestry, we tested the association between lung function measures (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio; n = 306 476) and cognitive traits including nine cognitive function test scores (n = 32 321–428 609), all-cause dementia, Alzheimer’s disease and vascular dementia (6805, 2859 and 1544 cases, respectively, and ∼421 241 controls). In the same population, we derived summary statistics for associations between common genetic variants in 55 lung development genes and lung function measures and cognitive traits using adjusted linear/logistic regression models. Using a hypothesis-driven Bayesian co-localization analysis, we finally investigated the presence of shared genetic signals between lung function measures and cognitive traits at each of these 55 genes. Higher lung function measures were generally associated with higher scores of cognitive function tests as well as lower risk of dementia. The strongest association was between forced vital capacity and vascular dementia (adjusted hazard ratio 0.74 per standard deviation increase, 95% confidence interval 0.67–0.83). Of the 55 genes of interest, we found shared variants in four genes, namely: CSNK2B rs9267531 (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence and pairs matching), NFATC3 rs548092276 & rs11275011 (forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence), PTCH1 rs2297086 & rs539078574 (forced expiratory volume in 1 s to forced vital capacity ratio with reaction time) and KAT8 rs138259061 (forced vital capacity with pairs matching). However, the direction of effects was not in keeping with our hypothesis, i.e. variants associated with lower lung function were associated with better cognitive function or vice versa. We also found distinct variants associated with lung function and cognitive function in KAT8 (forced vital capacity and Alzheimer’s disease) and PTCH1 (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence and reaction time). The links between CSNK2B and NFATC3 and cognitive traits have not been previously reported by genome-wide association studies. Despite shared genes and variants, our findings do not support the hypothesis that shared developmental signalling pathways explain the association of lower adult lung function with poorer cognitive function.
Zoon balanitis: not a distinct clinicopathological entity?
Authors: Watchorn Richard E , Doyle Claire , Kravvas Georgios , Bunker Christopher B 
Published: November 2024

Abstract
Zoon balanitis (ZB) was originally described in the 1950s in patients with clinical features resembling erythroplasia of Queyrat but with histology that demonstrated a plasma cell infiltrate without evidence of dysplasia. Subsequently, ZB has been extensively reported in the literature, reflecting widespread acknowledgement as an established distinct clinicopathological entity. However, its existence as such has been questioned, and there have been suggestions in the literature that ZB represents either a nonspecific irritant reaction pattern, or a part of the heterogeneous clinicopathological complex of male genital lichen sclerosus (MGLSc). In this study, the entire historical literature of published cases of ZB was subject to review to determine whether clinical or histological features of MGLSc had been present and been overlooked. In total, 101 papers were reviewed. Seventy-five contained images purporting to be of ZB. Images that were deemed to be of inadequate quality or to present uninformative anatomical views were excluded. The images in 66 papers were amenable to scrutiny; 98.5% of these images demonstrated clinical signs of MGLSc, such as adhesions, effacement of the coronal sulcus and the frenulum, tightening of the prepuce, constrictive posthitis, etiolation of the glans, lichenoid inflammation and sclerosis. These findings strongly suggest that ZB occurs in the vast majority of cases as a manifestation of MGLSc and that its recognition as a distinct clinicopathological entity should be questioned, if not discontinued.
Protean cutaneous manifestation caused by ABCA12 variants: erythrokeratodermia variabilis-like ichthyosis and unique palmoplantar keratoderma
Authors: Chang Chih-Yu , Yang Min-Chia , Cheng Hui-Ching , Lin Yu-Chen , McGrath John , Hsu Chao-Kai , Tu Wei Ting 
Published: November 2024

Abstract
ABCA12 is crucial for skin barrier function and is traditionally linked to severe congenital ichthyoses, such as harlequin ichthyosis. However, its genotype–phenotype relationship may be more nuanced. Using whole-exome sequencing and Sanger sequencing, we identified four cases of mild ichthyosis with biallelic ABCA12 pathogenic variants. In addition to a milder phenotype, the palmoplantar keratoderma (PPK) in these cases had a distinct ‘mosaic tile-like’ pattern. Two cases with missense variants in the N-terminus of ABCA12 also presented an annular ichthyosis pattern resembling erythrokeratodermia variabilis et progressiva. Our findings suggest a correlation between ABCA12 missense variant location and clinical presentation, expanding the phenotypic spectrum associated with ABCA12 variants and highlighting the potential for annular patterns or ‘mosaic tile-like’ PPK in these patients.
Adiponectin and Risk of Psoriasis: Observational and Mendelian Randomization Studies in up to 900 000 Individuals
Authors: Nielsen Maria B , Benn Marianne , Nordestgaard Børge G , Skov Lone , Çolak Yunus 
Published: October 2024

Abstract

Background
Psoriasis is a chronic inflammatory skin disorder often associated with obesity. Adiponectin, an anti-inflammatory protein-hormone secreted by adipose tissue, may be a link between obesity and psoriasis. We hypothesized that low plasma adiponectin is associated with an increased risk of psoriasis in observational and causal genetic studies.

Methods
In observational analyses, we used information on plasma adiponectin and psoriasis in 30 045 individuals from the Copenhagen General Population Study (CGPS). In one-sample Mendelian randomization analyses, we used genetic information on adiponectin and psoriasis in 107 308 individuals from the CGPS. In two-sample Mendelian randomization analyses, we used genetic information on adiponectin from the ADIPOGen consortium and genetic information on psoriasis in 373 338 and 462 933 individuals from the FinnGen study and UK Biobank (UKB).

Results
In observational analyses, a 1-unit log-transformed higher plasma adiponectin was associated with a hazard ratio (HR) for psoriasis of 0.67 (95% confidence interval: 0.48–0.94) in an age- and sex-adjusted model but not in a multivariable adjusted model including obesity measures with a HR of 0.95 (0.66–1.35). In genetic one-sample Mendelian randomization analysis, a 1-unit log-transformed higher plasma adiponectin was not associated with a causal risk ratio for psoriasis of 1.33 (0.77–2.32) in the CGPS. In two-sample Mendelian randomization analyses, a 1-unit log-transformed higher plasma adiponectin was not associated with causal risk ratios for psoriasis of 0.96 (0.81–1.14) in FinnGen and 1.00 (1.00–1.01) in UKB.

Conclusions
Low plasma adiponectin is associated with increased risk of psoriasis in age- and sex-adjusted observational analyses; however, this was not the case after adjustment for obesity measures or in causal genetic analyses.
External validation of SCORE2-Diabetes in The Netherlands across various socioeconomic levels in native-Dutch and non-Dutch populations
Authors: Alfaraj Sukainah A , Kist Janet M , Groenwold Rolf H H , Spruit Marco , Mook-Kanamori Dennis , Vos Rimke C 
Published: November 2024

Abstract

Aims
Adults with type 2 diabetes have an increased risk of cardiovascular events (CVEs), the world’s leading cause of mortality. The SCORE2-Diabetes model is a tool designed to estimate the 10-year risk of CVE specifically in individuals with type 2 diabetes. However, the performance of such models may vary across different demographic and socioeconomic groups, necessitating validation and assessment in diverse populations. This study aims to externally validate SCORE2-Diabetes and assess its performance across various socioeconomic and migration origins in The Netherlands.

Methods and results
We selected adults with type 2 diabetes, aged 40–79 years and without previous CVE from the Extramural LUMC Academic Network (ELAN) primary care data cohort from 2007 to 2023. ELAN data were linked with Statistics Netherlands registry data to obtain information about the country of origin and socioeconomic status (SES). Cardiovascular event was defined as myocardial infarction, stroke, or CV mortality. Non-CV mortality was considered a competing event. Analyses were stratified by sex, Dutch vs. other non-Dutch countries of origin, and quintiles of SES. Of the 26 544 included adults with type 2 diabetes, 2518 developed CVE. SCORE2-Diabetes showed strong predictive accuracy for CVE in the Dutch population [observed-to-expected ratio (OE) = 1.000, 95% CI = 0.990–1.008 for men, and OE = 1.050, 95% CI = 1.042–1.057 for women]. For non-Dutch individuals, the model underestimated CVE risk (OE = 1.121, 95% CI = 1.108–1.131 for men, and OE = 1.100, 95% CI = 1.092–1.111 for women). The model also underestimated the CVE risk (OE &gt; 1) in low SES groups and overestimated the risk (OE &lt; 1) in high SES groups. Discrimination was moderate across subgroups with c-indices between 0.6 and 0.7.

Conclusion
SCORE2-Diabetes accurately predicted the risk of CVE in the Dutch population. However, it underpredicted the risk of CVE in the low SES groups and non-Dutch origins, while overpredicting the risk in high SES men and women. Additional clinical judgment must be considered when using SCORE2-Diabetes for different SES and countries of origin.

Lay summary
A new study validates the SCORE2-Diabetes model for predicting a 10-year risk of cardiovascular events in type 2 diabetes. Strong accuracy for the Dutch population, but underestimation of the risk for low SES and non-Dutch groups. SCORE2-Diabetes should be used with extra caution across diverse subgroups.
Two-year outcomes of Micra AV leadless pacemakers in the Micra AV CED study
Authors: El-Chami Mikhael F , Higuera Lucas , Longacre Colleen , Stromberg Kurt , Crossley George , Piccini Jonathan P 
Published: November 2024

Abstract

Aims
Leadless pacing is a safe and effective alternative to transvenous pacing for bradycardia. Micra AV is a leadless, single-device solution that provides atrioventricular synchronous ventricular pacing therapy. Early results from the Micra AV CED study showed reductions in short-term complications associated with the Micra AV leadless pacemaker among US Medicare patients. The objective of this study is to compare chronic complications, re-interventions, and all-cause mortality at 2 years between patients implanted with a Micra AV leadless pacemaker and a traditional dual-chamber transvenous (DC-TV) pacemaker.

Methods and results
Patients implanted with a Micra AV leadless pacemaker (n = 7552) or a DC-TV pacemaker (n = 110 558) in 2020 and 2021 were identified using device registration-linked Medicare administrative claims data. Competing risk models compared the unadjusted and propensity score overlap weight–adjusted complication, re-intervention, and all-cause mortality rates of Micra AV and DC-TV patients at 2 years. Micra AV patients had significantly more comorbidities (end-stage renal disease 14.9 vs. 2.0%, P &lt; 0.0001; renal dysfunction 47.9 vs. 34.2%, P &lt; 0.0001; diabetes 46.2 vs. 38.3%, P &lt; 0.001; congestive heart failure 41.4 vs. 30.6%, P &lt; 0.0001). Two years post-implant, Micra AV patients had lower complication rates [adjusted 5.3 vs. 9.6%, hazard ratio (HR): 0.54, 95% confidence interval (CI) 0.49–0.61, P &lt; 0.0001] and lower re-intervention rates (adjusted 3.5 vs. 5.6%, HR: 0.62, 95% CI 0.54–0.72, P &lt; 0.0001) than DC-TV patients. Upgrades to cardiac resynchronization therapy were low in both groups (adjusted 1.6 vs. 1.7%, P = 0.40), as were Micra AV upgrades to a dual-chamber system (adjusted 1.4%). All-cause mortality rates remained higher in Micra AV than in DC-TV patients (unadjusted HR: 2.48, 95% CI 2.35–2.62, P &lt; 0.0001; adjusted HR: 1.53, 95% CI 1.44–1.62, P &lt; 0.0001).

Conclusion
Patients implanted with Micra AV had lower complications and re-intervention rates at 2 years than patients implanted with a traditional DC-TV pacemaker. All-cause mortality remained higher in Micra AV patients, likely due to their higher comorbidity burden and other differences in baseline characteristics.

Clinical trial registration
ClinicalTrials.gov ID NCT04235491