bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis
Authors: Christiansen Christian Fynbo , Pottegård Anton , Heide-Jørgensen Uffe , Bodilsen Jacob , Søgaard Ole Schmeltz , Maeng Michael , Vistisen Simon Tilma , Schmidt Morten , Lund Lars Christian , Reilev Mette , Hallas Jesper , Voldstedlund Marianne , Husby Anders , Thomsen Marianne Kragh , Johansen Nanna Borup , Brun Nikolai Constantin , Thomsen Reimar Wernich , Bøtker Hans Erik , Sørensen Henrik Toft 
Published: December 2020

ObjectiveTo examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes.MethodsThis nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use.ResultsThe study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users.ConclusionsACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.Trial registration numberEUPAS34887
Clinical and diagnostic findings in a dog and a cat with congenital hypothyroidism
Authors: Hermans Michelle , Burger Nienke Christina , Kromhout Kaatje , Bhatti Sofie F M , Cornelis Ine 
Published: December 2020

A seven‐year‐old Miniature Schnauzer and a 16‐month‐old Domestic shorthair with clinical features of disproportionate dwarfism, presented with progressive thoracolumbar and cervical myelopathies, respectively. CT and MR imaging were performed in both patients revealing multiple thoracolumbar intervertebral disc protrusions located between T10 and L3 in the dog, and a cervical spinal arachnoid diverticulum at C2 in the cat as the cause for their myelopathic signs. Additionally, epiphysial dysgenesis of the vertebral column and shortened vertebrae were noticed. The history of hypothyroidism in the dog and the low serum thyroxine and elevated thyroid stimulating hormone concentration in the cat, together with the clinical presentations and the skeletal deformities, resulted in the diagnosis of congenital hypothyroidism in both patients. Congenital hypothyroidism is known to cause vertebral deformities and joint laxity, which possibly contributed in both cases to the development of the myelopathic disorders. Surgical treatment, combined with levothyroxine therapy, resulted in successful outcomes.
Asymptotic analysis of Feynman diagrams and their maximal cuts
Authors: Ananthanarayan B. , Das Abhijit B. , Sarkar Ratan 
Published: December 2020

AbstractThe ASPIRE program, which is based on the Landau singularities and the method of Power geometry to unveil the regions required for the evaluation of a given Feynman diagram asymptotically in a given limit, also allows for the evaluation of scaling coming from the top facets. In this work, we relate the scaling having equal components of the top facets of the Newton polytope to the maximal cut of given Feynman integrals. We have therefore connected two independent approaches to the analysis of Feynman diagrams.
Aspirin Use and Prostate Cancer among African-American Men in the Southern Community Cohort Study
Authors: Tang Wei , Fowke Jay H. , Hurwitz Lauren M. , Steinwandel Mark , Blot William J. , Ambs Stefan 
Published: December 2020

Abstract

Background:
The association of aspirin use with prostate cancer has been investigated, but few studies included African-American men. Here, we analyzed the relationship of aspirin intake with prostate cancer risk and mortality among African-American men in the Southern Community Cohort Study (SCCS).

Methods:
SCCS recruited 22,426 African-American men between 2002 and 2009. Aspirin use was assessed at enrollment. Our exposures of interest were any aspirin use (regular strength, low-dose or baby aspirin, or half tablets of aspirin) and regular strength aspirin. Each exposure variable was compared with nonusers. Associations between aspirin use and prostate cancer risk and mortality were examined with Cox proportional hazards models.

Results:
At enrollment, 5,486 men (25.1%) reported taking any aspirin and 2,634 men (12.1%) reported regular strength aspirin use. During follow-up (median, 13 years), 1,058 men developed prostate cancer, including 103 prostate cancer–specific deaths. Aspirin use was not associated with prostate cancer development [adjusted HR, 1.07; 95% confidence interval (CI), 0.92–1.25 for any aspirin use and HR, 0.97; 95% CI, 0.78–1.19 for regular strength aspirin], but was suggestively associated with reduced prostate cancer mortality (HR, 0.66; 95% CI, 0.39–1.14 for any aspirin use and HR, 0.41; 95% CI, 0.17–1.00 for regular strength aspirin).

Conclusions:
Aspirin use at enrollment was tentatively associated with reduced prostate cancer mortality, but not risk, among African-American men in SCCS.

Impact:
Prospective SCCS data suggest that aspirin use may help prevent lethal prostate cancer among this high-risk group of men.
Combined BRAF, MEK, and CDK4/6 Inhibition Depletes Intratumoral Immune-Potentiating Myeloid Populations in Melanoma
Authors: Lelliott Emily J. , Mangiola Stefano , Ramsbottom Kelly M. , Zethoven Magnus , Lim Lydia , Lau Peter K.H. , Oliver Amanda J. , Martelotto Luciano G. , Kirby Laura , Martin Claire , Patel Riyaben P. , Slater Alison , Cullinane Carleen , Papenfuss Anthony T. , Haynes Nicole M. , McArthur Grant A. , Oliaro Jane , Sheppard Karen E. 
Published: December 2020

Abstract
Combined inhibition of BRAF, MEK, and CDK4/6 is currently under evaluation in clinical trials for patients with melanoma harboring a BRAFV600 mutation. While this triple therapy has potent tumor-intrinsic effects, the impact of this combination on antitumor immunity remains unexplored. Here, using a syngeneic BrafV600ECdkn2a−/−Pten−/− melanoma model, we demonstrated that triple therapy promoted durable tumor control through tumor-intrinsic mechanisms and promoted immunogenic cell death and T-cell infiltration. Despite this, tumors treated with triple therapy were unresponsive to immune checkpoint blockade (ICB). Flow cytometric and single-cell RNA sequencing analyses of tumor-infiltrating immune populations revealed that triple therapy markedly depleted proinflammatory macrophages and cross-priming CD103+ dendritic cells, the absence of which correlated with poor overall survival and clinical responses to ICB in patients with melanoma. Indeed, immune populations isolated from tumors of mice treated with triple therapy failed to stimulate T-cell responses ex vivo. While combined BRAF, MEK, and CDK4/6 inhibition demonstrates favorable tumor-intrinsic activity, these data suggest that collateral effects on tumor-infiltrating myeloid populations may impact antitumor immunity. These findings have important implications for the design of combination strategies and clinical trials that incorporate BRAF, MEK, and CDK4/6 inhibition with immunotherapy for the treatment of patients with melanoma.
The Cistercian Mission in Transylvania
Authors: Dincă Adinel C. , Schabel Chris 
Published: December 2020

Abstract
Just before 1200 and just after 1240 two Cistercian abbeys, first a male house at Cârța, not far from Sibiu (Sancta Maria in Kerz), and then a nunnery in Brașov (Sancta Katherina), were established in Transylvania, a borderland of the territories ruled by the Hungarian crown inhabited by Eastern-rite Christians, especially Romanians. Conventionally, often following the model of older historiography on Frankish Greece, modern scholars have understood the arrival of the Cistercian Order in this remote area as an effort at conversion initiated by the papal see. Reassessing older evidence within a new historiographical paradigm and adding newly discovered documentary sources, this paper argues instead that the Cistercian mission in Transylvania was tied to local factors, cultural, social, and economic, and thus the White Monks endured as long as their cooperation with the elite of the German colonists in southern Transylvania remained fruitful. In the light of the evidence, and similar to parallel developments in Frankish Greece, neither ethnic conflict nor a desire to convert non-Latins played a determining role in the historical evolution of the Cistercian presence in Transylvania.
Revisiting the Quasi-Biennial Oscillation as Seen in ERA5. Part II: Evaluation of Waves and Wave Forcing
Authors: Pahlavan Hamid A. , Wallace John M. , Fu Qiang , Kiladis George N. 
Published: December 2020

AbstractThis paper describes stratospheric waves in ERA5 and evaluates the contributions of different types of waves to the driving of the quasi-biennial oscillation (QBO). Because of its higher spatial resolution compared to its predecessors, ERA5 is capable of resolving a broader spectrum of waves. It is shown that the resolved waves contribute to both eastward and westward accelerations near the equator, mainly by the way of the vertical flux of zonal momentum. The eastward accelerations by the resolved waves are mainly due to Kelvin waves and small-scale gravity (SSG) waves with zonal wavelengths smaller than 2000 km, whereas the westward accelerations are forced mainly by SSG waves, with smaller contributions from inertio-gravity and mixed Rossby–gravity waves. Extratropical Rossby waves disperse upward and equatorward into the tropical region and impart a westward acceleration to the zonal flow. They appear to be responsible for at least some of the irregularities in the QBO cycle.
Teaching Middle Ear Anatomy and Basic Ear Surgery Skills: A Qualitative Study Comparing Endoscopic and Microscopic Techniques
Authors: Anschuetz Lukas , Siggemann Till , Dür Cilgia , Dreifuss Corinne , Caversaccio Marco , Huwendiek Sören 
Published: December 2020

ObjectiveEndoscopic ear surgery is gaining popularity as a minimally invasive surgical technique for middle ear diseases. Its ongoing implementation into clinical routine has consequences regarding teaching of middle ear anatomy and surgery. To improve undergraduate and postgraduate training, we investigated the perception of and preference for endoscopy as compared with microscopy at different educational levels.Study DesignQualitative study based on a thematic analysis approach.SettingTertiary academic medical center.MethodsAfter a standardized curriculum was run on endoscopic and microscopic anatomy and surgical skills education, 5 focus groups were held. The interviews were conducted, video recorded, transcribed, and analyzed. Analysis of the data gave rise to 11 themes showing the participants’ perceptions and preferences.ResultsFive medical students, 11 otorhinolaryngology residents, and 3 staff members participated in this qualitative study. For anatomy teaching, there was a clear preference for the endoscopic technique. The main advantages were the enhanced overview and perception of the anatomic details provided through endoscopy. For skills acquisition, the perceived advantages of the techniques were the same view of the surgical field for endoscopy and the 2‐handed surgical technique for microscopy. However, there was no clear preference between the techniques for skills acquisition.ConclusionThe endoscopic technique was generally judged more beneficial for teaching anatomy, especially due to the greater visualization of the complex middle ear anatomy. Given that both techniques will remain important to future surgeons, the relative unique benefits of each must be considered when designing and optimizing curricula for otologic education.
The role of the interosseous ligament in forearm rotation: A bio-mechanical study
Authors: Kholinne Erica , Kwak Jae-Man , Sun Yucheng , Koh Kyoung-Hwan , Jeon In-Ho 
Published: December 2020

Background: Management of longitudinal forearm instability remains challenging. Chronic forearm stability may be overcome by reconstruction of the interosseous ligament (IOL). Despite the bands of the IOL being inseparable, studies of the IOL have focused on the central band (CB), but have neglected the proximal (PB) and distal (DB) bands. The purpose of this study was to characterize the bio-mechanical properties of the IOL. Materials and Methods: Twelve frozen specimens from individuals of both sexes were bio-mechanically analyzed using a custom-designed jig operated at constant angular speed to simulate forearm rotation. Strain was measured during dynamic forearm simulation using a motion tracking system. Results: The average strain of the CB, PB, and DB during forearm simulation were 0.08 ± 0.04, 0.83 ± 0.47, and 0.65 ± 0.23 mm (p < 0.001). The IOL was generally shortest during maximal pronation and increased as the forearm was rotated to a neutral position. The strain of the CB remain constant during forearm rotation and was the lowest at full pronation to 20° pronation position. Throughout forearm rotation, the strain of the CB remained constant, whereas the strain of the PB and DB fluctuated. Conclusions: The PB, CB, and DB of the forearm IOL have different bio-mechanical properties. CB maintained a constant rotational strain throughout forearm rotation. Strain on the CB was significantly lower than strains on the PB and DB. By contrast, strains on the PB and DB varied, suggesting that their roles differ from those of the CB. When CB reconstruction is needed, graft should be tensioned at 20° forearm pronation to gain optimum tension.
What information do patients want about their medicines? An exploration of the perspectives of general medicine inpatients
Authors: Chan Amy Hai Yan , Aspden Trudi , Brackley Kim , Ashmore-Price Hannah , Honey Michelle 
Published: December 2020

Abstract
Background
Medicines are one of the most common healthcare interventions, yet evidence shows patients often do not receive the information they want about their medicines. This affects their adherence and healthcare engagement. There is limited research exploring what information patients want about their medicines, from whom and in what format. The aim of this study was to determine the medicines information needs of patients admitted to the general medical service of a large New Zealand (NZ) hospital, and identify the barriers and enablers to meeting these needs.

Methods
A descriptive exploratory approach using semi-structured interviews was used to understand the needs and preferences of patients for information about their regular medicines and the barriers and facilitators to obtaining this information. Patients admitted to a general medical ward at a large NZ hospital, aged 18 years and over, prescribed one or more regular medicines, and self-managing their own medicines prior to hospitalisation were included. Semi-structured interviews were conducted with each participant (n = 30) and transcribed, then analysed using a general inductive thematic analysis approach.

Results
Five overarching themes captured the medicines information needs of patients: (1) autonomy; (2) fostering relationships; (3) access; (4) communication; and (5) minimal information needs. Patients desired information to facilitate their decision-making and self-management of their health. Support people, written information, and having good relationships with health providers enabled this. Having access to information at the right time, communicated in a clear and consistent way with opportunities for follow-up, was important. A significant portion of participants were satisfied with receiving minimal information and had no expectations of needing more medicines information.

Conclusions
Although patients’ medicines information needs varied between individuals, the importance of receiving information in an accessible, timely manner, and having good relationships with health providers, were common to most. Considering these needs is important to optimise information delivery in general medical patients.
Positive association between dietary acid load and future insulin resistance risk: findings from the Korean Genome and Epidemiology Study
Authors: Lee Kyung Won , Shin Dayeon 
Published: December 2020

Abstract
Background
Acid-base homeostasis is increasingly being recognized to play an important role in normal metabolic function. However, prospective studies on the relationship between diet-induced acid-base imbalance and insulin resistance among Asian populations have been limited. Thus, we investigated whether diet-induced metabolic acidosis was prospectively associated with insulin resistance risk in middle-aged and older Korean adults.

Methods
In total, 5406 participants from the Korean Genome and Epidemiology Study without type 2 diabetes, insulin resistance, cancer, or renal diseases at baseline examination were included in this study. To estimate diet-induced metabolic acidosis, we used potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from the usual dietary intake assessed by a validated 103-item food frequency questionnaire at baseline. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of insulin resistance incidence.

Results
During a mean follow-up period of 7.4 years, we documented 3449 insulin resistance cases. In the fully adjusted model, the future insulin resistance risk was significantly higher among participants in the highest quartiles of PRAL (HR: 1.30, 95% CI: 1.13–1.48, Ptrend = 0.0002) and NEAP (HR: 1.30, 95% CI: 1.14–1.49, Ptrend = 0.0008) than among those in the lowest quartiles. Associations were slightly strengthened among men, adults < 50 years old, obese participants, or those with low physical activity levels.

Conclusions
Our findings suggested that diet-dependent acid load was positively associated with the future development of insulin resistance, suggesting effect modification by sex, age, the presence of obesity, and physical activity levels.
Follistatin-like 1 (FSTL1) is a prognostic biomarker and correlated with immune cell infiltration in gastric cancer
Authors: Li Li , Huang Shanshan , Yao Yangyang , Chen Jun , Li Junhe , Xiang Xiaojun , Deng Jun , Xiong Jianping 
Published: December 2020

AbstractBackgroundFollistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated.MethodsThe expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real-time quantitative PCR (RT-qPCR) were used to analyze protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates were analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA), and LinkedOmics database.ResultsThe expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC.ConclusionsThe study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks, and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.
Microglial TonEBP mediates LPS-induced inflammation and memory loss as transcriptional cofactor for NF-κB and AP-1
Authors: Jeong Gyu Won , Lee Hwan Hee , Lee-Kwon Whaseon , Kwon Hyug Moo 
Published: December 2020

Abstract
Background
Microglia are brain-resident myeloid cells involved in the innate immune response and a variety of neurodegenerative diseases. In macrophages, TonEBP is a transcriptional cofactor of NF-κB which stimulates the transcription of pro-inflammatory genes in response to LPS. Here, we examined the role of microglial TonEBP.

Methods
We used microglial cell line, BV2 cells. TonEBP was knocked down using lentiviral transduction of shRNA. In animals, TonEBP was deleted from myeloid cells using a line of mouse with floxed TonEBP. Cerulenin was used to block the NF-κB cofactor function of TonEBP.

Results
TonEBP deficiency blocked the LPS-induced expression of pro-inflammatory cytokines and enzymes in association with decreased activity of NF-κB in BV2 cells. We found that there was also a decreased activity of AP-1 and that TonEBP was a transcriptional cofactor of AP-1 as well as NF-κB. Interestingly, we found that myeloid-specific TonEBP deletion blocked the LPS-induced microglia activation and subsequent neuronal cell death and memory loss. Cerulenin disrupted the assembly of the TonEBP/NF-κB/AP-1/p300 complex and suppressed the LPS-induced microglial activation and the neuronal damages in animals.

Conclusions
TonEBP is a key mediator of microglial activation and neuroinflammation relevant to neuronal damage. Cerulenin is an effective blocker of the TonEBP actions.
Complete remission of heavily treated ovarian clear cell carcinoma with ARID1A mutations after pembrolizumab and bevacizumab combination therapy: a case report
Authors: Lin Yu-Chien , Wen Kuo-Chang , Sung Pi-Lin , Chou Yu-Ting , Liew Phui-Ly , Chen Lin-Yu , Huang Rui-Lan , Lai Hung-Cheng , Chang Lu-Te 
Published: December 2020

Abstract
Background
Patients with ovarian clear cell carcinoma (OCCC) have a poor prognosis because they show low sensitivity to platinum-based chemotherapy. New treatments for refractory OCCC are urgently needed.

Case presentation
We present a patient with refractory OCCC in whom conventional chemotherapy failed. Cachexia was induced by the disseminating recurrent tumors. Tumor tissue staining and genomic analysis revealed PD-L1 negativity, a low tumor burden, stable microsatellite instability, and two mutations in ARID1A. The patient was administered pembrolizumab combined with bevacizumab triweekly. Her serum CA-125 level decreased dramatically after the first cycle. A computerized tomography scan showed marked regression of the recurrent masses after 3 cycles, and the patient reached complete remission after 9 cycles. She showed good recovery from cachexia. We observed no marked side effects except for mild polyarthritis of the small joints.

Conclusions
The therapeutic effect of checkpoint inhibitors combined with angiogenesis inhibitors is very promising in our patient with OCCC. Further clinical trials of tumors including ARID1A mutations are warranted.