bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type 2 diabetes epidemic and key risk factors in Qatar: a mathematical modeling analysis
Authors: Awad Susanne F , A Toumi Amine , A Al-Mutawaa Kholood , A Alyafei Salah , A Ijaz Muhammad , A H Khalifa Shamseldin , B Kokku Suresh , C M Mishra Amit , V Poovelil Benjamin , B Soussi Mounir , G El-Nahas Katie , O Al-Hamaq Abdulla , A Critchley Julia , H Al-Thani Mohammed , Abu-Raddad Laith J 
Published: May 2022

IntroductionWe aimed to characterize and forecast type 2 diabetes mellitus (T2DM) disease burden between 2021 and 2050 in Qatar where 89% of the population comprises expatriates from over 150 countries.Research design and methodsAn age-structured mathematical model was used to forecast T2DM burden and the impact of key risk factors (obesity, smoking, and physical inactivity). The model was parametrized using data from T2DM natural history studies, Qatar’s 2012 STEPwise survey, the Global Health Observatory, and the International Diabetes Federation Diabetes Atlas, among other data sources.ResultsBetween 2021 and 2050, T2DM prevalence increased from 7.0% to 14.0%, the number of people living with T2DM increased from 170 057 to 596 862, and the annual number of new T2DM cases increased from 25 007 to 45 155 among those 20–79 years of age living in Qatar. Obesity prevalence increased from 8.2% to 12.5%, smoking declined from 28.3% to 26.9%, and physical inactivity increased from 23.1% to 26.8%. The proportion of incident T2DM cases attributed to obesity increased from 21.9% to 29.9%, while the contribution of smoking and physical inactivity decreased from 7.1% to 6.0% and from 7.3% to 7.2%, respectively. The results showed substantial variability across various nationality groups residing in Qatar—for example, in Qataris and Egyptians, the T2DM burden was mainly due to obesity, while in other nationality groups, it appeared to be multifactorial.ConclusionsT2DM prevalence and incidence in Qatar were forecasted to increase sharply by 2050, highlighting the rapidly growing need of healthcare resources to address the disease burden. T2DM epidemiology varied between nationality groups, stressing the need for prevention and treatment intervention strategies tailored to each nationality.
Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis
Authors: Li Jing , Du Heyue , Wang Yang , Aertgeerts Bert , Guyatt Gordon , Hao Qiukui , Shen Yanjiao , Li Ling , Su Na , Delvaux Nicolas , Bekkering Geertruida , Khan Safi U , Riaz Irbaz B , Vandvik Per Olav , Su Baihai , Tian Haoming , Li Sheyu 
Published: May 2022

ObjectiveTo determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy.MethodsThis systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard care or active lipid-lowering comparators in people who need lipid-lowering therapy with the follow-up duration of at least 24 weeks. We summarised the relative effects for potential harms from PCSK9 inhibitors using random-effect pairwise meta-analyses and assessed the certainty of evidence using GRADE (Grading of Recommendation Assessment, Development and Evaluation) for each outcome.ResultsWe included 32 trials with 65 861 participants (with the median follow-up duration of 40 weeks, ranging from 24 to 146 weeks). The meta-analysis showed an incidence of injection-site reaction leading to discontinuation (absolute incidence of 15 events (95% CI 11 to 20) per 1000 persons in a 5-year time frame, high certainty evidence). PCSK9 inhibitors do not increase the risk of new-onset diabetes mellitus, neurocognitive events, cataracts or gastrointestinal haemorrhage with high certainty evidence. PCSK9 inhibitors probably do not increase the risks of myalgia or muscular pain leading to discontinuation or any adverse events leading to discontinuation with moderate evidence certainty. Given very limited evidence, PCSK9 inhibitors might not increase influenza-like symptoms leading to discontinuation (risk ratio 1.5; 95% CI 0.06 to 36.58). We did not identify credible subgroup analyses results, including shorter versus longer follow-up duration of trials.ConclusionsPCSK9 inhibitors slightly increase the risk of severe injection-site reaction but not cataracts, gastrointestinal haemorrhage, neurocognitive events, new-onset diabetes or severe myalgia or muscular pain.
The effects of roadways on lakes and ponds: a systematic review and assessment of knowledge gaps
Authors: Dixon Heather J. , Elmarsafy Mariam , Hannan Natasha , Gao Vivian , Wright Caitlin , Khan Layana , Gray Derek K. 
Published: May 2022

As the global population increases, the expansion of road networks has led to the destruction and disturbance of terrestrial and aquatic habitats. Road-related stressors have significant effects on both lotic and lentic habitats. While there are several systematic reviews that evaluate the effects of roads on lotic environments, there are none that consider their effects on lentic habitats only. We conducted a literature review to achieve two objectives: (1) to summarize the effects of roads on the physical, chemical, and biological properties of lentic environments; and (2) to identify biases and gaps in our current knowledge of the effects of roads on lentic habitats, so that we could find promising areas for future research.Our review found 172 papers published between 1970 and 2020. The most frequently studied stressors associated with roads included road salt and heavy metal contamination (67 and 43 papers, respectively), habitat fragmentation (37 papers), and landscape change (14 papers). These stressors can lead to alterations in conductivity and chloride levels, changes in lake stratification patterns, increases in heavy metal concentrations in water and organisms, and significant mortality as amphibians disperse across roadways. We also identified a variety of other stressors that may be understudied based on their frequency of appearance in our search results, including polycyclic aromatic hydrocarbons, road dust, increased accessibility, hydrological changes, noise pollution, dust suppressants, sedimentation, invasive species introductions, and water withdrawal.Our review indicated that there are strong geographic biases in published studies, with 57.0% examining North American sites and 30.2% examining European sites. Furthermore, there were taxonomic biases in the published literature, with most studies focusing on amphibians (41.7%), fish (15.6%), and macroinvertebrates (14.6%), while few considered zooplankton (8.3%), diatoms (7.3%), amoebas (5.2%), water birds (3.1%), reptiles (2.1%), and macrophytes (1.0%). Based on our review, we have identified promising areas for future research for each of the major stressors related to roadways. However, we speculate that rectifying the geographic and taxonomic bias of our current knowledge could significantly advance our understanding of the impacts of roads on lentic environments, thereby better informing environmental management of these important habitats.
Cosmic evolution in DHOST theory with scaling solutions
Authors: Thipaksorn Wittaya , Karwan Khamphee 
Published: May 2022

AbstractWe study cosmic evolution based on the fixed points in the dynamical analysis of the degenerate higher-order scalar-tensor (DHOST) theories. We consider the DHOST theory in which the propagation speed of gravitational waves is equal to the speed of light, the tensor perturbations do not decay to dark energy perturbations, and the scaling solutions exist. The scaling fixed point associated with late-time acceleration of the universe can be either stable or saddle depending on the parameters of the theory. For some ranges of the parameters, this scaling fixed point and field-dominated fixed point can be simultaneously stable. Cosmic evolution will reach either the scaling attractor or the field-dominated attractor depending on the sign of the time derivative of the scalar field in the theory during the matter domination. The density parameter of dark matter can be larger than unity before reaching the scaling attractor if the deviation from Einstein’s theory of gravity is too large. For this DHOST theory, stabilities of $${\phi }$$
ϕ
-matter-dominated epoch ($$\phi $$
ϕ
MDE) and field-dominated solutions are similar to the coupled dark energy models in Einstein gravity even though gravity is described by different theories. In our consideration, the universe can only evolve from the $$\phi $$
ϕ
MDE regime to the field-dominated regime. The ghost and gradient instabilities up to linear order in cosmological perturbations have been investigated. There is no gradient instability, while the ghost instability can be avoided for some range of the model parameters.
Clinical Performance of Triage Strategies for Hr-HPV–Positive Women; A Longitudinal Evaluation of Cytology, p16/K-67 Dual Stain Cytology, and HPV16/18 Genotyping
Authors: Stanczuk Grazyna , Currie Heather , Forson William , Baxter Gwendoline , Lawrence James , Wilson Allan , Palmer Timothy , Arbyn Marc , Cuschieri Kate 
Published: May 2022

Abstract

Background:
We evaluated the longitudinal performance of three options: HPV16/18 genotyping (HPV16/18), cytology (LBC), and p16/Ki-67 dual stain cytology (DS) for the triage of high-risk Human Papillomavirus–positive (Hr-HPV+) women within the cervical screening program in Scotland.

Methods:
Data were derived from a cohort of Hr-HPV+ women (n = 385) who participated in PaVDaG (Papillomavirus Dumfries and Galloway) study. Performance of triage strategies for detecting high-grade disease was assessed at 3 (in women &lt;50 years) or 5 years (in women &gt;50 years). Sensitivity, specificity, PPV, and cNPV of each triage test were calculated for CIN2+ and CIN3+ when used singly or sequentially.

Results:
The sensitivity of LBC (≥ borderline), DS, and HPV 16/18 genotyping for the detection of CIN2+ was 62.7% (50.7–73.3), 77.7% (63.1–83.7), and 62.7% (50.7–73.3) with corresponding cNPVs of 10.9%, 8.4%, and 11.9%. The option with the highest sensitivity and lowest cNPV was HPV 16/18 genotyping followed by LBC of Hr-HPV other+ and then DS of the LBC negatives. This yielded sensitivity of 94.7% (86.2–98.3) and cNPV 2.7% for CIN2+. Triage performance was similar if women had tested Hr-HPV+ positive by vaginal self-sampling.

Conclusions:
Two-step triage with HPV 16/18 genotyping before LBC (or DS) for Hr-HPV other+ women was associated with a lower risk of significant disease at follow-up compared with single triage approaches.

Impact:
This study provides longitudinal performance data on triage strategies in Hr-HPV+ women and will be informative for the evolution of cervical screening programs that increasingly rely on molecular technologies.
Evaluating the Potential of Polygenic Risk Score to Improve Colorectal Cancer Screening
Authors: Arnau-Collell Coral , Díez-Villanueva Anna , Bellosillo Beatriz , Augé Josep M. , Muñoz Jenifer , Guinó Elisabet , Moreira Leticia , Serradesanferm Anna , Pozo Àngels , Torà-Rocamora Isabel , Bonjoch Laia , Ibañez-Sanz Gemma , Obon-Santacana Mireia , Moratalla-Navarro Ferran , Sanz-Pamplona Rebeca , Márquez Márquez Carmen , Rueda Miret Rebeca , Pérez Berbegal Rocio , Piquer Velasco Gabriel , Hernández Rodríguez Cristina , Grau Jaume , Castells Antoni , Borràs Josep M. , Bessa Xavier , Moreno Victor , Castellví-Bel Sergi 
Published: May 2022

Abstract

Background:
Colorectal cancer has high incidence and associated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario.

Methods:
We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were genotyped. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated.

Results:
Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02–1.06; P &lt; 0.0001]. A 2-fold increase in colorectal cancer risk was observed for subjects in the highest decile of risk alleles (≥65), compared with those in the first decile (≤54; OR = 2.22; 95% CI, 1.59–3.12; P &lt; 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62–0.66].

Conclusions:
This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers.

Impact:
PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers.
Association of Blood Pressure with Prostate Cancer Risk by Disease Severity and Prostate Cancer Death: A Pooled Cohort Study
Authors: Jochems Sylvia H.J. , Häggström Christel , Stattin Pär , Järvholm Bengt , Stocks Tanja 
Published: May 2022

Abstract

Background:
The association of blood pressure (BP) with prostate cancer risk after accounting for asymptomatic prostate-specific antigen (PSA) testing, and with prostate cancer death, is unclear.

Methods:
We investigated BP, measured at a mean age of 38 years among 430,472 men from five Swedish cohorts, in association with incident prostate cancer (n = 32,720) and prostate cancer death (n = 6718). HRs were calculated from multivariable Cox regression models.

Results:
Increasing systolic and diastolic BP levels combined were associated with a slightly lower prostate cancer risk, with a HR of 0.98 (95% CI, 0.97–0.99) per standard deviation (SD) of mid-BP (average of systolic and diastolic BP). The association was restricted to the PSA era (1997 onwards, HR, 0.96; 95% CI, 0.95–0.98), to diagnoses initiated by a PSA test in asymptomatic men (HR, 0.95; 95% CI, 0.93–0.97), and to low-risk prostate cancer (HR, 0.95; 95% CI, 0.92–0.97). There was no clear association with more advanced disease at diagnosis. In cases, a slightly higher risk of prostate cancer death was observed for higher BP levels (HR, 1.05; 95% CI, 1.01–1.08) per SD of mid-BP; however, the association was restricted to distant metastatic disease (Pheterogeneity between case groups = 0.01), and there was no association for BP measured less than 10 years prior to diagnosis.

Conclusions:
Prediagnostic BP is unlikely an important risk factor for prostate cancer development and death. Less asymptomatic PSA testing among men with higher BP levels may explain their lower risk of prostate cancer.

Impact:
Elevated BP is unlikely to be an important risk factor for prostate cancer.
A High-Throughput Screening Platform Identifies Novel Combination Treatments for Malignant Peripheral Nerve Sheath Tumors
Authors: Fernández-Rodríguez Juana , Creus-Bachiller Edgar , Zhang Xiaohu , Martínez-Iniesta Maria , Ortega-Bertran Sara , Guha Rajarshi , Thomas Craig J. , Wallace Margaret R. , Romagosa Cleofe , Salazar-Huayna Lourdes , Reilly Karlyne M. , Blakely Jaishri O. , Serra-Musach Jordi , Pujana Miguel Angel , Serra Eduard , Villanueva Alberto , Ferrer Marc , Lázaro Conxi 
Published: May 2022

AbstractMalignant peripheral nerve sheath tumors (MPNST) are soft-tissue sarcomas that are the leading cause of mortality in patients with Neurofibromatosis type 1 (NF1). Single chemotherapeutic agents have shown response rates ranging from 18% to 44% in clinical trials, so there is still a high medical need to identify chemotherapeutic combination treatments that improve clinical prognosis and outcome. We screened a collection of compounds from the NCATS Mechanism Interrogation PlatE (MIPE) library in three MPNST cell lines, using cell viability and apoptosis assays. We then tested whether compounds that were active as single agents were synergistic when screened as pairwise combinations. Synergistic combinations in vitro were further evaluated in patient-derived orthotopic xenograft/orthoxenograft (PDOX) athymic models engrafted with primary MPNST matching with their paired primary-derived cell line where synergism was observed. The high-throughput screening identified 21 synergistic combinations, from which four exhibited potent synergies in a broad panel of MPNST cell lines. One of the combinations, MK-1775 with Doxorubicin, significantly reduced tumor growth in a sporadic PDOX model (MPNST-SP-01; sevenfold) and in an NF1-PDOX model (MPNST-NF1–09; fourfold) and presented greater effects in TP53 mutated MPNST cell lines. The other three combinations, all involving Panobinostat (combined with NVP-BGT226, Torin 2, or Carfilzomib), did not reduce the tumor volume in vivo at noncytotoxic doses. Our results support the utility of our screening platform of in vitro and in vivo models to explore new therapeutic approaches for MPNSTs and identified that combination MK-1775 with Doxorubicin could be a good pharmacologic option for the treatment of these tumors.
Endothelial Cell TGF-β (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency
Authors: Taniguchi Ryosuke , Ohashi Yuichi , Lee Jung Seok , Hu Haidi , Gonzalez Luis , Zhang Weichang , Langford John , Matsubara Yutaka , Yatsula Bogdan , Tellides George , Fahmy Tarek M. , Hoshina Katsuyuki , Dardik Alan 
Published: May 2022

Background:
Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-β (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation—critical components of wall thickness—we hypothesized that disruption of TGF-β signaling prevents excessive wall thickening during venous remodeling.

Methods:
A mouse aortocaval fistula model was used. SB431542—an inhibitor of TGF-β receptor I—was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-β receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses.

Results:
Inhibition of TGF-β signaling with SB431542-containing nanoparticles significantly reduced p-Smad2–positive cells in the AVF wall during the early maturation phase (days 7–21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-β signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell–specific TGF-β signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency.

Conclusions:
Endothelial cell–targeted TGF-β inhibition may be a translational strategy to improve AVF patency.
Early Neurologic Deterioration with Symptomatic Isolated Internal Carotid Artery Occlusion: A Cohort Study, Systematic Review, and Meta‐Analysis
Authors: Khazaal Ossama , Neale Natalie , Acton Emily K. , Husain Muhammad R. , Kung David , Cucchiara Brett , Kasner Scott E. 
Published: May 2022

Background
Acute endovascular revascularization for isolated internal carotid occlusion without tandem intracranial occlusion has been proposed to prevent early neurologic deterioration (END) and improve outcome, but has not been shown to be more effective than medical therapy. We aimed to evaluate prognosis with initial medical therapy alone, and also performed a systematic review to put these results in a broader context.

Methods
We performed a retrospective cohort study of patients admitted over a 2‐year period with acute stroke/transient ischemic attack due to isolated internal carotid artery occlusion. Subjects with tandem intracranial occlusion or Alberta Stroke Program Early CT Score (ASPECTS) ≤5 were excluded. The primary outcome was END within 48 hours (National Institute of Health Stroke Scale [NIHSS] increase ≥4 persisting for ≥24 hours). Secondary outcomes included discharge NIHSS and disposition. We also performed a systematic review and meta‐analysis of published studies along with the data from our cohort.

Results
Twenty‐three patients met our inclusion criteria. Median age was 69 years, initial Alberta Stroke Program Early CT Score 10, and NIHSS score 3. END attributed to recurrent ischemia occurred in 5/23 patients (22%, 95% CI: 7%–44%). At discharge, 78% had a favorable outcome with a median NIHSS of 2 (interquartile range 1–3). END appeared more frequent in those with higher baseline NIHSS. In our systematic review, 7 prior studies met our inclusion criteria. END occurred in 17% (95% CI: 12%–23%) of patients, 18% with medical therapy versus 13% with endovascular therapy, with substantial heterogeneity among studies.

Conclusion
In patients with acute stroke or transient ischemic attack due to isolated internal carotid occlusion, END is relatively common (occurring in about 1 out of 6 patients). Further research is needed to evaluate the roles of maximal medical management or acute endovascular thrombectomy in these patients.
A Neighborhood Framework for Resource-Lean Content Flagging
Authors: Sarwar Sheikh Muhammad , Zlatkova Dimitrina , Hardalov Momchil , Dinkov Yoan , Augenstein Isabelle , Nakov Preslav 
Published: May 2022

Abstract
We propose a novel framework for cross- lingual content flagging with limited target- language data, which significantly outperforms prior work in terms of predictive performance. The framework is based on a nearest-neighbor architecture. It is a modern instantiation of the vanilla k-nearest neighbor model, as we use Transformer representations in all its components. Our framework can adapt to new source- language instances, without the need to be retrained from scratch. Unlike prior work on neighborhood-based approaches, we encode the neighborhood information based on query– neighbor interactions. We propose two encoding schemes and we show their effectiveness using both qualitative and quantitative analysis. Our evaluation results on eight languages from two different datasets for abusive language detection show sizable improvements of up to 9.5 F1 points absolute (for Italian) over strong baselines. On average, we achieve 3.6 absolute F1 points of improvement for the three languages in the Jigsaw Multilingual dataset and 2.14 points for the WUL dataset.