bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untangling fracture risk in monoclonal gammopathy of undetermined significance: A population‐based cohort study
Authors: Rögnvaldsson Sæmundur , Aspelund Thor , Thorsteinsdóttir Sigrún , Turesson Ingemar , Björkholm Magnus , Landgren Ola , Kristinsson Sigurður Yngvi 
Published: April 2021

AbstractObjectiveMonoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population‐based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden.MethodsData on fractures, PN, and confounders were acquired from high‐quality registers in Sweden.ResultsMonoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21‐1.37; P < .001 and HR: 1.34; 95% CI: 1.16‐1.55; P < .001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27‐2.16; P < .001). Fractures were not associated with long‐term risk of MGUS progression (HR: 1.08; 95% CI: 0.77‐1.53; P = .64).DiscussionBased on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS.
Improving Ki67 assessment concordance by the use of an artificial intelligence‐empowered microscope: a multi‐institutional ring study
Authors: Cai Lijing , Yan Kezhou , Bu Hong , Yue Meng , Dong Pei , Wang Xinran , Li Lina , Tian Kuan , Shen Haocheng , Zhang Jun , Shang Jiuyan , Niu Shuyao , Han Dandan , Ren Chen , Huang Junzhou , Han Xiao , Yao Jianhua , Liu Yueping 
Published: April 2021

AimsThe nuclear proliferation biomarker Ki67 plays potential prognostic and predictive roles in breast cancer treatment. However, the lack of interpathologist consistency in Ki67 assessment limits the clinical use of Ki67. The aim of this article was to report a solution utilising an artificial intelligence (AI)‐empowered microscope to improve Ki67 scoring concordance.Methods and resultsWe developed an AI‐empowered microscope in which the conventional microscope was equipped with AI algorithms, and AI results were provided to pathologists in real time through augmented reality. We recruited 30 pathologists with various experience levels from five institutes to assess the Ki67 labelling index on 100 Ki67‐stained slides from invasive breast cancer patients. In the first round, pathologists conducted visual assessment on a conventional microscope; in the second round, they were assisted with reference cards; and in the third round, they were assisted with an AI‐empowered microscope. Experienced pathologists had better reproducibility and accuracy [intraclass correlation coefficient (ICC) = 0.864, mean error = 8.25%] than inexperienced pathologists (ICC = 0.807, mean error = 11.0%) in visual assessment. Moreover, with reference cards, inexperienced pathologists (ICC = 0.836, mean error = 10.7%) and experienced pathologists (ICC = 0.875, mean error = 7.56%) improved their reproducibility and accuracy. Finally, both experienced pathologists (ICC = 0.937, mean error = 4.36%) and inexperienced pathologists (ICC = 0.923, mean error = 4.71%) improved the reproducibility and accuracy significantly with the AI‐empowered microscope.ConclusionThe AI‐empowered microscope allows seamless integration of the AI solution into the clinical workflow, and helps pathologists to obtain higher consistency and accuracy for Ki67 assessment.
Impact of temperature on obstructive sleep apnoea in three different climate zones of Europe: Data from the European Sleep Apnoea Database (ESADA)
Authors: Staats Richard , Bailly Sébastien , Bonsignore Maria Rosaria , Ryan Silke , Riha Renata L. , Schiza Sophia , Verbraecken Johan , Basoglu Ozen K. , Saaresranta Tarja , Pataka Athanasia , Ludka Ondrej , Lombardi Carolina , Hedner Jan Anders , Grote Ludger ,   the European Sleep Apnoea Database (ESADA) collaborators
Published: April 2021

SummaryRecent studies indicate that ambient temperature may modulate obstructive sleep apnoea (OSA) severity. However, study results are contradictory warranting more investigation in this field. We analysed 19,293 patients of the European Sleep Apnoea Database (ESADA) cohort with restriction to the three predominant climate zones according to the Köppen–Geiger climate classification: Cfb (warm temperature, fully humid, warm summer), Csa (warm temperature, summer dry, hot summer), and Dfb (snow, fully humid, warm summer). Average outside temperature values were obtained and several hierarchical regression analyses were performed to investigate the impact of temperature on the apnea–hypopnea index (AHI), oxygen desaturation index (ODI), time of oxygen saturation <90% (T90) and minimum oxygen saturation (MinSpO2) after controlling for confounders including age, body mass index, gender, and air conditioning (A/C) use. AHI and ODI increased with higher temperatures with a standardised coefficient beta (β) of 0.28 for AHI and 0.25 for ODI, while MinSpO2 decreased with a β of −0.13 (all results p < .001). When adjusting for climate zones, the temperature effect was only significant in Cfb (AHI: β = 0.11) and Dfb (AHI: β = 0.08) (Model 1: p < .001). The presence of A/C (3.9% and 69.3% in Cfab and Csa, respectively) demonstrated only a minor increase in the prediction of the variation (Cfb: AHI, R2 +0.003; and Csa: AHI, R2 +0.007; both p < .001). Our present study indicates a limited but consistent influence of environmental temperature on OSA severity and this effect is modulated by climate zones.
Static spherically symmetric three-form stars
Authors: Barros Bruno J. , Haghani Zahra , Harko Tiberiu , Lobo Francisco S. N. 
Published: April 2021

AbstractWe consider interior static and spherically symmetric solutions in a gravity theory that extends the standard Hilbert–Einstein action with a Lagrangian constructed from a three-form field $$A_{\alpha \beta \gamma }$$

A

α
β
γ

, which generates, via the field strength and a potential term, a new component in the total energy-momentum tensor of the gravitational system. We formulate the field equations in Schwarzschild coordinates and investigate their solutions numerically for different equations of state of neutron and quark matter, by assuming that the three-field potential is either a constant or possesses a Higgs-like form. Moreover, stellar models, described by the stiff-fluid, radiation-like, bag model and the Bose–Einstein condensate equations of state are explicitly obtained in both general relativity and three-form gravity, thus allowing an in-depth comparison between the astrophysical predictions of these two gravitational theories. As a general result we find that, for all the considered equations of state, three-form field stars are more massive than their general relativistic counterparts. As a possible astrophysical application, we suggest that the 2.5$$ M_{\odot }$$

M
⊙

mass compact object, associated with the GW190814 gravitational wave event, could be in fact a neutron or a quark star described by the three-form gravity theory.
A simplified estimate of the effective reproduction number $$R_t$$ using its relation with the doubling time and application to Italian COVID-19 data
Authors: Bonifazi Gianluca , Lista Luca , Menasce Dario , Mezzetto Mauro , Pedrini Daniele , Spighi Roberto , Zoccoli Antonio 
Published: April 2021

AbstractA simplified method to compute $$R_t$$

R
t

, the effective reproduction number, is presented. The method relates the value of $$R_t$$

R
t

to the estimation of the doubling time performed with a local exponential fit. The condition $$R_t=1$$

R
t

=
1

corresponds to a growth rate equal to zero or equivalently an infinite doubling time. Different assumptions on the probability distribution of the generation time are considered. A simple analytical solution is presented in case the generation time follows a gamma distribution.
Analysis of risk factors of bladder neck contracture following transurethral surgery of prostate
Authors: Chen Yi-Zhong , Lin Wun-Rong , Chow Yung-Chiong , Tsai Wei-Kung , Chen Marcelo , Chiu Allen W. 
Published: April 2021

Abstract
Backgrounds
The aim of the present study was to investigate the perioperative parameters associated with bladder neck contracture (BNC) after transurethral surgery of the prostate and to compare the incidence of BNC after transurethral resection of the prostate (TURP) or Thulium vaporesection (resection group) versus Thulium vapoenucleation or enucleation of the prostate (enucleation group).

Methods
Between March 2008 and March 2020, 2363 patients received TURP and 1656 patients received transurethral surgery of the prostate with Thulium laser (ThuP) at Mackay Memorial Hospital. A total of 62 patients developed BNC. These BNC patients were age-and operation-matched to 124 randomly sampled TURP/ThuP controls without BNC. A 1:1 propensity score matching model was used to evaluate the difference in incidence of BNC.

Results
Our study demonstrated that a greater proportion of BNC patients had history of cerebrovascular accidents (11/62 vs. 7/124, p = 0.009), coronary artery disease (14/48 vs. 16/108, p = 0.03), chronic kidney disease (14/62 vs. 11/124, p = 0.01), and two or more comorbidities (29/62 vs. 27/124, p = 0.001) compared with NBNC patients. Multivariate analysis showed that smaller prostate volume (OR 0.96 (0.94–0.99), p = 0.008) and recatherization (OR 5.6 (1.02–30.6), p = 0.047) were significantly associated with BNC. A ROC curve predicted that a prostate volume < 42.9 cm3 was associated with a notably higher rate of BNC. The propensity score matching model reported there was no difference in incidence between resection and enucleation groups.

Conclusion
This study demonstrated that incidence of BNC was the same in different surgical techniques and that low prostate volume, recatherization and ≥ 2 comorbidities were positively correlated with the development of BNC after TURP or ThuP.
Stochastic approximation method using diagonal positive-definite matrices for convex optimization with fixed point constraints
Authors: Iiduka Hideaki 
Published: April 2021

AbstractThis paper proposes a stochastic approximation method for solving a convex stochastic optimization problem over the fixed point set of a quasinonexpansive mapping. The proposed method is based on the existing adaptive learning rate optimization algorithms that use certain diagonal positive-definite matrices for training deep neural networks. This paper includes convergence analyses and convergence rate analyses for the proposed method under specific assumptions. Results show that any accumulation point of the sequence generated by the method with diminishing step-sizes almost surely belongs to the solution set of a stochastic optimization problem in deep learning. Additionally, we apply the learning methods based on the existing and proposed methods to classifier ensemble problems and conduct a numerical performance comparison showing that the proposed learning methods achieve high accuracies faster than the existing learning method.
More than meets the naked eye: an unusual psoriatic arthritis mimicry and the important role of dermoscopic examination
Authors: Anne Lim Jo , Rahim Mohd Jazman Che , Ghazali Wan Syamimee Wan , Ahmed Wan Aireene Wan , Isa Seoparjoo Azmel Mohd 
Published: April 2021

AbstractBackgroundPsoriatic arthritis (PsA) can manifest in various forms. This includes mimicry of other diseases. We describe an unusual mimicry of PsA.Case presentationWe report a case of a middle-aged lady who presented with severe pain and morning stiffness over the small joints of the left hand for 3 months and painless deformity of the affected joints 1 year before. She was under treatment for pruritic rash over her ankles and knees for the past 1 year as well. Physical examination revealed a fixed flexion deformity, swelling and tenderness of the left ring and little fingers’ distal interphalangeal (DIP) joints. Left hand radiograph showed sclerotic joint margin, narrowed joint space and marginal osteophytes of the affected DIP joints. Dermoscopic examination showed red- violaceous, flat-topped papules and plaques with minimal scales on both ankles; hyperpigmented scaly plaques over both knees and vertical fingernail ridges. Serum autoimmune screening and inflammatory markers were unremarkable. Left ankle skin biopsy showed features consistent of psoriasis. PsA was diagnosed. Weekly titrated oral methotrexate and topical steroid were started. The patient showed significant improvement after 1 month of treatment.ConclusionPsA is a great mimicker. Dermoscopy is an accessible and valuable tool to assess skin lesions in greater detail. Clinicians should be aware of coexisting diseases or misdiagnosis when patients do not respond to treatment.
Denosumab might prevent periprosthetic bone loss after total hip and knee arthroplasties: a review
Authors: Xu Jianda , Li Huan , Qu Yuxing , Zheng Chong , Wang Bin , Shen Pengfei , Xie Zikang , Wei Kang , Wang Yan , Zhao Jianning 
Published: April 2021

AbstractTotal hip arthroplasty and total knee arthroplasty are extensively used for the treatment of the end-stage degenerative joint diseases. Currently, periprosthetic bone loss is still the major cause of aseptic loosening, resulting in implant failures. Previous literature introduced some widely accepted protocols for the prevention and treatment of periprosthetic bone loss, but no guideline has been proposed. Denosumab, a human monoclonal immunoglobulin G2 (IgG2) antibody, can inhibit bone resorption by binding to the receptor activator of nuclear factor kappa-B ligand (RANKL). This article reviews the present findings and evidence concerning the effect of denosumab on the periprosthetic bone loss after total hip arthroplasty and total knee arthroplasty. Overall, the current evidence suggests that denosumab is a promising agent for the treatment of periprosthetic bone loss.
Preoperative Amlodipine Is Efficacious in Preventing Intraoperative HDI in Pheochromocytoma: Pilot RCT
Authors: Jaiswal Sanjeet Kumar , Memon Saba Samad , Lila Anurag , Sarathi Vijaya , Goroshi Manjunath , Garg Robin , Barnabas Rohit , Hemantkumar Indrani , Patel Rajendra D , Oak Shrikanta , Dalvi Abhay , Garale Mahadeo , Patil Virendra , Shah Nalini S , Bandgar Tushar 
Published: April 2021

Abstract

Context
Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce.

Objective
We aimed to compare the efficacy of CCB and α-blockers on intraoperative hemodynamic instability (HDI) in PPGL.

Methods
In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure ≥ 160 mmHg) and hypotension (mean arterial pressure &lt; 60 mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anesthesia to skin closure).

Results
The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 ± 18.4% vs 2.44 ± 2.4%; CI, 8.68-32.14%; P 0.002) were significantly higher in the prazosin GITS arm than the amlodipine arm, whereas episodes and duration of hypotension did not differ between the 2 groups. There was no perioperative mortality. One patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine).

Conclusion
Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.
Clinical Practice Guidelines on the Diagnosis and Management of Polycystic Ovary Syndrome: A Systematic Review and Quality Assessment Study
Authors: Al Wattar Bassel H , Fisher Maria , Bevington Laura , Talaulikar Vikram , Davies Melanie , Conway Gerrad , Yasmin Ephia 
Published: April 2021

Abstract

Context
Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS).

Evidence Acquisition
We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool.

Evidence Synthesis
We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease (12/13, 92%), followed by cardiovascular risk assessment (10/13, 77%). Mental health (8/13, 62%) and diagnosis in adolescents (7/13, 54%) were the least reported domains. Most CPGs had a high quality for scope and purpose description (12/13, 92%) while stakeholder’s involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs (2/13, 15%). We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS.

Conclusion
Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates.
HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study
Authors: Yamamoto Rain , Jensen Majken K , Aroner Sarah , Furtado Jeremy D , Rosner Bernard , Hu Frank B , Balkau Beverley , Natali Andrea , Ferrannini Ele , Baldi Simona , Sacks Frank M 
Published: April 2021

Abstract

Context
High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects.

Objective
We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3.

Design, Setting, and Participants
A prospective cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and cardiovascular disease (RISC) study, a multicenter European clinical investigation, whose recruitment initiated in 2002, with a follow-up of 3 years.

Main Measures
Insulin sensitivity was estimated from an oral glucose tolerance test at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich enzyme-linked immunosorbent assay (ELISA)-based method.

Results
The 2 HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (P-trend = 0.01), compared to the lowest quintile. No significant association was observed for total HDL, and very low density lipoprotein (VLDL) and low density lipoprotein (LDL) containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III.

Conclusion
Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.
Adolescent Tri-ponderal Mass Index Growth Trajectories and Incident Diabetes Mellitus in Early Adulthood
Authors: Wu Yi-Fan , Fan Hsien-Yu , Chen Yang-Ching , Kuo Kuan-Liang , Chien Kuo-Liong 
Published: April 2021

Abstract

Purpose
Studies have reported the influence of adolescent obesity on development of adult diabetes, but the effect of the growth pattern during this period has rarely been explored. Also, the tri-ponderal mass index (TMI) was thought to be a better estimation of adolescent body fat levels than the body mass index (BMI), so we sought to investigate whether growth trajectories derived by these two indices could predict incident diabetes.

Methods
We conducted a study by using the Taipei City Hospital Radiation Building Database, a longitudinal cohort established in 1996. Physical exam results including blood test results were collected annually and the BMI z-score/TMI growth trajectory groups during 13 to 18 years of age were identified using growth mixture modeling. A Cox proportional hazard model for incident diabetes was used to examine the risk of baseline obese status and different BMI/TMI growth trajectories.

Results
Five growth trajectory groups were identified for the BMI z-score and the TMI. During approximately 20 400 person-years follow-up, 33 of 1387 participants developed diabetes. Baseline obesity defined by the BMI z-score and the TMI were both related to adult diabetes. The persistent increase TMI growth trajectory exhibited a significantly increased risk of diabetes after adjusting for baseline obese status and other correlated covariates (hazard ratio: 2.85, 95% confidence interval: 1.01-8.09). There was no association between BMI growth trajectory groups and incident diabetes.

Conclusions
A specific TMI growth trajectory pattern during adolescence might be critical for diabetes prevention efforts.