bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between SCN5A R225Q variant and dilated cardiomyopathy: potential role of intracellular pH and WNT/β-catenin pathway
Authors: Hu Jingjing , Yang Kun , Zhao Yongchao , Wei Zilun , Yang Lebing , Gao Rifeng , Wu Yonghui , Xu Lei , Xu Sujuan , Hu Kai , Sun Aijun , Ge Junbo 
Published: June 2022

BackgroundThe SCN5A variant is a common cause of familial dilated cardiomyopathy (DCM). We previously reported a SCN5A variant (c.674G>A), located in the high-risk S4 segment of domain I (DI-S4) region in patients with idiopathic DCM and R225Q knockin (p.R225Q) mice carrying the c.674G>A variant exhibited prolonged baseline PR intervals without DCM phenotypes. In this study, we explored the association and mechanism between R225Q variant and DCM phenotype.MethodsPrevalence of DI-S4 variant was compared between patients with idiopathic DCM and the control participants. R225Q knockin and wild-type (WT) mice were subjected to doxorubicin (DOX), D-galactose (D-gal) or D-gal combined with DOX.ResultsClinical data suggested that the prevalence of DI-S4 variant was higher in DCM group than in the control group (4/90 (4.4%) vs 3/1339 (0.2%), p<0.001). Cardiomyocytes from R225Q knockin mice treated with D-gal and DOX exhibited more significant hypertrophic phenotype and weaker contraction/dilation function and an increased level of apoptosis as compared with WT mice. Mechanistically, we found that R225Q variant could increase intracellular pH and further induce the activation of the WNT/β-catenin pathway as well as the overexpression of pro-hypertrophic and pro-apoptotic targets. WNT-C59 inhibitor improved cardiac function in the R225Q knockin mice treated with D-gal and DOX.ConclusionOur results suggest that R225Q variant is associated with increased susceptibility to DCM. Ageing could enhance this process via activating WNT/β-catenin signaling in response to increased intracellular pH. Antagonising the WNT/β-catenin pathway might be a potential therapeutic strategy for mitigating R225Q variant-related DCM pathogenesis.
Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (‘Registry’)
Authors: Erton Zeynep Belce , Sevim Ecem , de Jesús Guilherme Ramires , Cervera Ricard , Ji Lanlan , Pengo Vittorio , Ugarte Amaia , Andrade Danieli , Andreoli Laura , Atsumi Tatsuya , Fortin Paul R , Gerosa Maria , Zuo Yu , Petri Michelle , Sciascia Savino , Tektonidou Maria G , Aguirre- Zamorano Maria Angeles , Branch D Ware , Erkan Doruk 
Published: June 2022

ObjectivesTo describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry.MethodsWe identified persistently aPL-positive patients recorded as ‘pregnant’ during prospective follow-up, and defined‘aPL-related outcome’as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment.ResultsOf the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss <10 weeks gestation. Of the remaining 40 pregnancies: (1) 26 (65%) resulted in term live delivery (TLD), 4 (10%) in PTLD between 34.0 weeks and 36.6 weeks, 5 (12.5%) in PTLD before 34th week, and 5 (12.5%) in fetal death (two associated with genetic anomalies); and (2) The aPL-related composite outcome occurred in 9 (23%). One of 26 (4%) pregnancies with TLD, 3/4 (75%) with PTLD between 34.0 weeks and 36.6 weeks, and 3/5 (60%) with PTLD before 34th week were complicated with PEC, SGA and/or PI. Fifty of 55 (91%) pregnancies were in lupus anticoagulant positive subjects, as well as all pregnancies with aPL-related composite outcome.ConclusionIn our multicentre, international, aPL-positive cohort, of 55 first pregnancies observed prospectively, 15 (27%) were complicated by early pregnancy loss. Of the remaining 40 pregnancies, composite pregnancy morbidity was observed in 9 (23%) pregnancies.
Natural history of pituitary apoplexy: a long-term follow-up study
Authors: Shaikh Ayesha A , Williams David Michael , Stephens Jeffrey Wayne , Boregowda Kusuma , Udiawar Maneesh Vasanth , Price David E 
Published: June 2022

Abstract

Background and aims
Pituitary apoplexy (PA) is a rare neurosurgical emergency, associated with deficiency of one or more pituitary hormones. Few studies have explored the relative outcomes associated with conservative and neurosurgical intervention.

Methods
A retrospective evaluation of all patients with PA reviewed at Morriston Hospital was undertaken and diagnosis was obtained from Morriston database (Leicester Clinical Workstation database) between 1998 and 2019 from clinic letters and discharge summaries.

Results
Thirty-nine patients with PA were identified with a mean age of 74.5 years and 20 (51.3%) patients were women. Patients were followed up for a mean±SD 68.1±61.7 months. Twenty-three (59.0%) patients had a known pituitary adenoma. Commoner clinical presentations of PA were ophthalmoplegia or visual field loss. Following PA, 34 (87.2%) patients were noted to have a non-functioning pituitary adenoma (either pre-existing or new), while 5 (12.8%) patients had a pre-existing functional macroadenoma. Neurosurgical intervention was taken in 15 (38.5%) patients of which 3 (20.0%) patients also received radiotherapy, 2 (13.3%) patients had radiotherapy alone and the remainder managed conservatively. External ophthalmoplegia recovered in all cases. Visual loss remained in all cases. One (2.6%) patient with chromophobe adenoma had a significant second episode of PA requiring repeat surgery.

Conclusion
PA often occurs in patients with undiagnosed adenoma. Hypopituitarism commonly occurred following conservative or surgical treatment. External ophthalmoplegia resolved in all cases, however, visual loss did not recover. Pituitary tumour recurrence and further PA episodes are rare.

What is already known on this topic

What this study adds

How this study might affect research, practice or policy
Cryoanalgesia for shoulder pain: a motor-sparing approach to rotator cuff disease
Authors: Stogicza Agnes Reka , Peng Philip 
Published: June 2022

IntroductionRotator cuff disease is a common cause of musculoskeletal pain and disability, and the management can be challenging. Joint denervation emerges as a new technique, but the literature on shoulder neural ablation procedure is largely limited to pulsed radiofrequency due to the concern of motor impairment. We described a novel motor-sparing approach of cryoablation for the management of shoulder pain based on the recent literature on the innervation of shoulder.MethodsFour patients with a history of rotator cuff disease refractory to conservative therapy and not amenable to surgery underwent a ultrasound-guided cryoablation of the capsular branches of the shoulder joint after a positive diagnostic injection. The target articular branches were based on the anatomical landmarks described in recent publication. They were the acromial, superior and inferior branches of the suprascapular nerve, the anterior branch of the axillary nerve, the nerve to the subscapularis, which were all located around the superior, posterior and anterior glenoid. The lateral pectoral nerve articular branch was targeted at the coracoclavicular space.ResultsAll four patients experienced at least 60% pain relief with improvement in function for 6–12 months following the procedure without any clinical evidence of motor impairment. No adverse effect was observed.DiscussionBased on the current understanding of the glenohumeral joint articular branches and their relationship to the bony landmark, targeting the articular branches only was feasible and led to good outcomes. Further large prospective cohort study is needed.
Pollutants: a candidate as a new risk factor for osteoarthritis—results from a systematic literature review
Authors: Deprouw Camille , Courties Alice , Fini Jean-Baptiste , Clerget-Froidevaux Marie-Stéphanie , Demeneix Barbara , Berenbaum Francis , Sellam Jérémie , Louati Karine 
Published: June 2022

BackgroundConsidering non-classical environmental risk factors for osteoarthritis (OA), a systematic literature review (SLR) was performed to summarise existing knowledge on associations between OA and pollutants.MethodsPubMed was used to identify studies reporting data on OA and pollutants in humans (examples of MeSH terms: “Pesticides” or “Polychlorinated Biphenyls” or ‘Lead’). Reports included epidemiological clinical studies, pollutant assessments in ex vivo OA joint, and in vitro effects of pollutants on chondrocytes.ResultsAmong the 193 potentially relevant articles, 14 were selected and combined with 9 articles obtained by manual search. Among these 23 articles there were: (1) 11 epidemiological studies on the relationship between OA and pollutants exposure, (2) 8 on pollutant concentrations in ex vivo OA joint, (3) 4 on the in vitro effects of pollutants on human chondrocytes. Epidemiological studies investigating mainly chlorinated and fluorinated pollutants suggested a possible link with OA. In cross-sectional studies, radiographic knee OA prevalence increased with higher serum lead levels. There was also a relationship between serum lead levels and serum/urine joint biomarkers. A high concentration of heavy metals in the cartilage tidemark was found in ex vivo joints. In vitro, the viability of chondrocytes was reduced in presence of some pollutants. However, the level of knowledge currently remains low, justifying the need for new methodologically sound studies.ConclusionsThis SLR supports the hypothesis of a possible involvement of pollutants in OA disease risk. Large-scale epidemiological and biological studies and ideally big-data analysis are needed to confirm that pollutants could be risk factors for OA.
Improved patient-reported outcomes in patients with psoriatic arthritis treated with risankizumab: analysis of the Phase 3 trial KEEPsAKE 2
Authors: Ostor Andrew J K , Soliman Ahmed M , Papp Kim A , Padilla Byron , Wang Zailong , Eldred Ann , de Vlam Kurt , Kivitz Alan 
Published: June 2022

ObjectivesDetermine the impact of 24-week risankizumab (RZB) versus placebo (PBO) on patient-reported outcomes (PROs) in patients with psoriatic arthritis (PsA) and inadequate response to one or two biologics (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR).MethodsPatients in the Phase 3 trial, KEEPsAKE 2, were randomised (1:1) to RZB 150 mg or PBO by subcutaneous injection. PROs assessed: 36-Item Short-Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-Fatigue), Patient’s Assessment of Pain by visual analogue scale (VAS), Patient’s global assessment of disease activity (PtGA), EuroQoL-5 Dimension-5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment—PsA (WPAI-PsA). Least squares mean change from baseline at week 24 was compared between RZB versus PBO by mixed-effects repeated regression modelling.ResultsAt week 24, RZB versus PBO treatment resulted in significant differences (95% CIs) in mean change from baseline in ranked secondary endpoints SF-36 physical component summary score (3.9 (2.4 to 5.3); p<0.001) and FACIT-Fatigue (2.2 (0.6 to 3.9); p=0.009) and improvements in pain (–8.1 (–12.8 to –3.5)), PtGA (–8.8 (–13.5 to –4.2)) and EQ-5D-5L index (0.08 (0.04 to 0.11)) and VAS (5.9 (1.9 to 9.8)) (all nominal p<0.01). More RZB-treated versus PBO-treated patients reported improvements from baseline at week 24 in 7 of 8 SF-36 subdomains (nominal p<0.05). At week 24, more RZB-treated versus PBO-treated patients reported improvements in 3 of 4 WPAI-PsA domains (nominal p≤0.01).ConclusionOverall, RBZ treatment resulted in improvements in pain, fatigue, health-related quality of life and ability to perform work in Bio-IR and/or csDMARD-IR patients with PsA.Trial registration numberNCT03671148.
Two-parametric f(R) dark energy model and some observational constraints
Authors: Granda L. N. 
Published: June 2022

A modified [Formula: see text] viable model is proposed that behaves asymptotically as [Formula: see text]CDM and satisfies cosmological and local gravity constraints. Apart from a mass scale that is a priori defined, the model contains only one additional parameter, which is determined by the current value of the matter density parameter [Formula: see text]. Under the chameleon mechanism the model satisfies the thin shell restrictions for local gravity systems without imposing additional restrictions on model parameters. Signals of scalar–tensor regime in the growth of matter perturbations, are present. Using the mass scale to determine the matter density parameter today, the remaining free parameter covers the whole range of values needed to test the model against the more stringent constraints arising at galactic and galactic cluster scales. The finite time singularity of the model was analyzed. A comparison was made with known models with the same number of parameters.
Amplitudes meet cosmology: A (scalar) primer
Authors: Benincasa Paolo 
Published: June 2022

Here, we review the most recent progress in our understanding of quantum mechanical observables in cosmology in the perturbative regime. It relies on an approach that considers them directly as functions of the data at the spacelike boundary at future infinity prescinding from the explicit time evolution. It takes inspiration from the on-shell formulation of perturbative scattering amplitudes developed in the past 20 years: starting with the requirement of consistency with some fundamental principles such as causality, unitarity and locality, it provides different ways of phrasing and extracting predictions. In this review, we aim to provide a pedagogical treatment of the most recent insights about the analytic structure of the perturbative quantum mechanical observables in cosmology, its relation to fundamental principles as well as physical processes, and how such observables and their features emerge from novel well-defined mathematical objects with their own first principle definition. The review is divided into three parts: Part 0 discusses the definition of quantum mechanical observables in cosmology and some general principles; Part I reviews the boundary approach to the analysis and computation of the perturbative wave function of the universe; Part II provides an introduction to the combinatorial-geometrical description of cosmological processes in terms of cosmological polytopes.
Quantum fluctuations, particles and entanglement: A discussion towards the solution of the quantum measurement problems
Authors: Konishi Kenichi 
Published: June 2022

The quantum measurement problems are revisited from a new perspective. One of the main ideas of this work is that the basic entities of our world are various types of particles, elementary or composite. It follows that each elementary process, hence each measurement process at its core, is a space–time, pointlike, event. Another key idea is that, when a microsystem [Formula: see text] gets into contact with the experimental device, factorization of [Formula: see text] rapidly fails and entangled mixed states appear. The wave functions for the microsystem-apparatus coupled systems for different measurement outcomes then lack overlapping space–time support. It means that the aftermath of each measurement is a single term in the sum: a “wave function collapse.”Our discussion leading to a diagonal density matrix, [Formula: see text] shows how the information encoded in the wave function [Formula: see text] gets transcribed, via entanglement with the experimental device and environment, into the relative frequencies [Formula: see text] for various experimental results [Formula: see text].These results represent the first, significant steps towards filling in the logical gaps in the standard interpretation based on Born’s rule, and replacing it with a more natural one. Accepting objective reality of quantum fluctuations, independent of any experiments, and independently of human presence, one renounces the idea that in a fundamental, complete theory of Nature the result of each single experiment must necessarily be predictable.A few well-known puzzles such as the Schrödinger cat conundrum and the Einstein–Podolsky–Rosen (EPR) paradox are briefly reviewed: they can all be naturally explained away.
Efficacy and Safety of Rupatadine Fumarate Combined with Acupoint Application in Allergic Rhinitis Complicated with Diabetes
Authors: Liu Yu , Jiang Pengjun , Chen Xuqing , Zhang Wen , Shi Jun 
Published: June 2022

The prevalence of allergic rhinitis has exhibited an upward trend, and diabetes is a common endocrine metabolic disorder. Treatment of allergic rhinitis complicated with diabetes has been marginally explored. This study aimed to observe the effect of rupatadine fumarate combined with acupoint application in the treatment of allergic rhinitis complicated with diabetes and its effect on serum IgE levels. Totally 80 patients with allergic rhinitis complicated with diabetes admitted to our hospital from December 2019 to December 2020 were recruited and assigned to receive either rupatadine fumarate (control group) or rupatadine fumarate plus acupoint application (research group). The clinical observation indexes of the two groups of patients before and after treatment were analyzed, and the clinical efficacy of the two groups was evaluated. Rupatadine fumarate plus acupoint application was associated with a significantly higher efficacy (23 cases of markedly effective, 14 cases of effective, and 3 cases of ineffective) versus rupatadine fumarate alone (14 cases of markedly effective, 16 cases of effective, and 10 cases of ineffective) (χ2 = 4.501,

p

= 0.034). The immunoglobulin E (IgE) and nasal mucosal eosinophils (EOS) levels of the two groups of patients after treatment decreased significantly, and the research group had lower results (

p

< 0.05). Patients in the research group showed significantly lower syndrome scores than those in the control group (

p

< 0.05). Rupatadine fumarate plus acupoint application resulted in significantly lower physical sign scores and interleukin-4 (IL-4) levels and higher levels of interferon-gamma (INF-γ) versus rupatadine fumarate alone (

p

< 0.05). The two groups showed a similar incidence of adverse events (

p

> 0.05). Rupatadine fumarate plus acupoint application may offer a viable alternative for the treatment of allergic rhinitis as it alleviates the clinical symptoms, improves the treatment efficiency, and enhances the anti-allergic effect of the drug, with a high safety profile.
Adherence to General Diabetes and Foot Care Processes, with Prompt Referral, Are Associated with Amputation-Free Survival in People with Type 2 Diabetes and Foot Ulcers: A Scottish National Registry Analysis
Authors: Meza-Torres Bernardo , Cunningham Scott G. , Heiss Christian , Joy Mark , Feher Michael , Leese Graham P. , de Lusignan Simon , Carinci Fabrizio 
Published: June 2022

Aims. To compare different packages of care across care providers in Scotland on foot-related outcomes. Methods. A retrospective cohort study with primary and secondary care electronic health records from the Scottish Diabetes Registry, including 6,845 people with type 2 diabetes and a first foot ulcer occurring between 2013 and 2017. We assessed the association between exposure to care processes and major lower extremity amputation and death. Proportional hazards were used for time-to-event univariate and multivariate analyses, adjusting for case-mix characteristics and care processes. Results were expressed in terms of hazard ratios with 95% confidence intervals. Results. 2,243 (32.7%) subjects had a major amputation or death. Exposure to all nine care processes at all ages (

HR
=
0.63

; 95% CI: 0.58-0.69;

p
<
.001

) and higher foot care attendance in people aged >70 years (

HR
=
0.88

; 0.78-0.99;

p
=
.03

) were associated with longer major amputation-free survival.

Waiting

time
≥
12

weeks between ulceration and clinic attendance was associated with worse outcomes (

HR
=
1.59

; 1.37-1.84;

p
<
.001

). In

people
>
70

years, minor amputations were associated with improved major amputation-free survival (

HR
=
0.69

; 0.52-0.92;

p
=
.01

). Conclusions. Strict adherence to a standardised package of general diabetes care before foot ulceration, timely foot care after ulceration, and specific treatment pathways were associated with longer major amputation-free survival among a large cohort of people with type 2 diabetes in Scotland, with a larger impact on older age groups.
Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
Authors: Macauda Angelica , Clay-Gilmour Alyssa , Hielscher Thomas , Hildebrandt Michelle A.T. , Kruszewski Marcin , Orlowski Robert Z. , Kumar Shaji K. , Ziv Elad , Orciuolo Enrico , Brown Elizabeth E. , Försti Asta , Waller Rosalie G. , Machiela Mitchell J. , Chanock Stephen J. , Camp Nicola J. , Rymko Marcin , Raźny Małgorzata , Cozen Wendy , Várkonyi Judit , Piredda Chiara , Pelosini Matteo , Belachew Alem A. , Subocz Edyta , Hemminki Kari , Rybicka-Ramos Malwina , Giles Graham G. , Milne Roger L. , Hofmann Jonathan N. , Zaucha Jan Maciej , Vangsted Annette Juul , Goldschmidt Hartmut , Rajkumar S. Vincent , Tomczak Waldemar , Sainz Juan , Butrym Aleksandra , Watek Marzena , Iskierka-Jazdzewska Elżbieta , Buda Gabriele , Robinson Dennis P. , Jurczyszyn Artur , Dudziński Marek , Martinez-Lopez Joaquin , Sinnwell Jason P. , Slager Susan L. , Jamroziak Krzysztof , Reis Rui Manuel Vieira , Weinhold Niels , Bhatti Parveen , Carvajal-Carmona Luis G. , Zawirska Daria , Norman Aaron D. , Mazur Grzegorz , Berndt Sonja I. , Campa Daniele , Vachon Celine M. , Canzian Federico 
Published: June 2022

Abstract

Background:
Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival.

Methods:
We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed.

Results:
SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P &lt; 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09–1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01–1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant.

Conclusions:
Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS.

Impact:
This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.