bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with adherence to COVID-19 prevention measures in the Democratic Republic of the Congo (DRC): results of an online survey
Authors: Ditekemena John Dinanga , Nkamba Dalau Mukadi , Muhindo Hypolite Mavoko , Siewe Joseph Nelson Fodjo , Luhata Christophe , Van den Bergh Rafael , Tshefu Kitoto Antoinette , Van Damme Wim , Muyembe Jean Jacques , Colebunders Robert 
Published: January 2021

ObjectivesWe aimed to assess the level of adherence to COVID-19 preventive measures in the Democratic Republic of the Congo (DRC) and to identify factors associated with non-adherence.DesignA cross-sectional population-based online survey.SettingsThe study was conducted in 22 provinces of the DRC. Five provinces with a satisfactory number of respondents were included in the analysis: Haut Katanga, Kasaï-Central, Kasaï-Oriental, Kinshasa and North Kivu.ParticipantsThe participants were people aged ≥18 years, living in the DRC. A total of 3268 participants were included in the study analysis.InterventionsBoth convenience sampling (surveyors themselves contacted potential participants in different districts) and snowball sampling (the participants were requested to share the link of the questionnaire with their contacts) methods were used.Primary and secondary outcome measuresWe computed adherence scores using responses to 10 questions concerning COVID-19 preventive measures recommended by the WHO and the DRC Ministry of Health. We used logistic regression analysis with generalised estimating equations to identify factors of poor adherence. We also asked about the presence or absence of flu-like symptoms during the preceding 14 days, whether a COVID-19 test was done and the test result.ResultsData from 3268 participants were analysed. Face masks were not used by 1789 (54.7%) participants. Non-adherence to physical distancing was reported by 1364 (41.7%) participants. 501 (15.3%) participants did not observe regular handwashing. Five variables were associated with poor adherence: lower education level, living with other people at home, being jobless/students, living with a partner and not being a healthcare worker.ConclusionDespite compulsory restrictions imposed by the government, only about half of the respondents adhered to COVID-19 preventive measures in the DRC. Disparities across the provinces are remarkable. There is an urgent need to further explore the reasons for these disparities and factors associated with non-adherence.
Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial
Authors: Yaskolka Meir Anat , Rinott Ehud , Tsaban Gal , Zelicha Hila , Kaplan Alon , Rosen Philip , Shelef Ilan , Youngster Ilan , Shalev Aryeh , Blüher Matthias , Ceglarek Uta , Stumvoll Michael , Tuohy Kieran , Diotallevi Camilla , Vrhovsek Urska , Hu Frank , Stampfer Meir , Shai Iris 
Published: January 2021

ObjectiveTo examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss.DesignFor the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS).ResultsParticipants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all).ConclusionThe new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.Trial registration numberNCT03020186.
Blocking IL-17A enhances tumor response to anti-PD-1 immunotherapy in microsatellite stable colorectal cancer
Authors: Liu Chao , Liu Ruiqi , Wang Bojun , Lian Jie , Yao Yang , Sun Haoxiu , Zhang Chunhui , Fang Lin , Guan Xin , Shi Jiaqi , Han Shuling , Zhan Fei , Luo Shengnan , Yao Yuanfei , Zheng Tongsen , Zhang Yanqiao 
Published: January 2021

BackgroundImmune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.MethodsThe expression of programmed cell death-ligand 1 (PD-L1) and its regulation by miR-15b-5p were investigated in MSS CRC cell lines and tissues. The effects of miR-15b-5p on tumorigenesis and anti-PD-1 treatment sensitivity were verified both in vitro and in colitis-associated cancer (CAC) and APCmin/+murine models. In vivo efficacy and mechanistic studies were conducted using antibodies targeting IL-17A and PD-1 in mice bearing subcutaneous CT26 and MC38 tumors.ResultsEvaluation of clinical pathological specimens confirmed thatPD-L1mRNA levels are associated with CD8+ T cell infiltration and better prognosis. miR-15b-5p was found to downregulate the expression of PD-L1 at the protein level, inhibit tumorigenesis and enhance anti-PD-1 sensitivity in CAC and APCmin/+CRC models. IL-17A led to high PD-L1 expression in CRC cells through regulating the P65/NRF1/miR-15b-5p axis. Combined IL-17A and PD-1 blockade had efficacy in CT26 and MC38 tumors, with more cytotoxic T lymphocytes cells and fewer myeloid-derived suppressor cells in tumors.ConclusionsIL-17A increases PD-L1 expression through the p65/NRF1/miR-15b-5p axis and promotes resistance to anti-PD-1 therapy. Blocking IL-17A improved the efficacy of anti-PD-1 therapy in MSS CRC murine models. IL-17A might serve as a therapeutic target to sensitize patients with MSS CRC to ICI therapy.
Estrogen receptor beta signaling in CD8+ T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch
Authors: Yuan Bin , Clark Curtis A , Wu Bogang , Yang Jing , Drerup Justin M , Li Tianbao , Jin Victor X , Hu Yanfen , Curiel Tyler J , Li Rong 
Published: January 2021

BackgroundThe non-overlapping functions of the two estrogen receptor subtypes, ERα (Estrogen Receptor α)and ERβ (Estrogen Receptor β), in tumor cells have been studied extensively. However, their counterparts in host cells is vastly underinterrogated. Even less is known about how ERα and ERβ activities are regulated in a subtype-specific manner. We previously identified a phosphotyrosine residue (pY36) of human ERβ that is important for tumor ERβ to inhibit growth of breast cancer cells in vitro and in vivo. A role of this ERβ phosphotyrosine switch in regulating host ERβ remains unclear.Conventional gene editing was used to mutate the corresponding tyrosine residue of endogenous mouse ERβ (Y55F) in mouse embryonic stem cells. The derived homozygous mutant Esr2Y55F/Y55F mouse strain and its wild-type (WT) counterpart were compared in various transplant tumor models for their ability to support tumor growth. In addition, flow cytometry-based immunophenotyping was carried out to assess antitumor immunity of WT and mutant hosts. Adoptive transfer of bone marrow and purified CD8+ T cells were performed to identify the host cell type that harbors ERβ-dependent antitumor function. Furthermore, cell signaling assays were conducted to compare T cell receptor (TCR)-initiated signaling cascade in CD8+ T cells of WT and mutant mice. Lastly, the ERβ-selective agonist S-equol was evaluated for its efficacy to boost immune checkpoint blockade (ICB)-based anticancer immunotherapy.Disabling the ERβ-specific phosphotyrosine switch in tumor-bearing hosts exacerbates tumor growth. Further, a cell-autonomous ERβ function was defined in CD8+ effector T cells. Mechanistically, TCR activation triggers ERβ phosphorylation, which in turn augments the downstream TCR signaling cascade via a non-genomic action of ERβ. S-equol facilitates TCR activation that stimulates the ERβ phosphotyrosine switch and boosts anti-PD-1 (Programmed cell death protein 1) ICB immunotherapy.Our mouse genetic study clearly demonstrates a role of the ERβ phosphotyrosine switch in regulating ERβ-dependent antitumor immunity in CD8+ T cells. Our findings support the development of ERβ agonists including S-equol in combination with ICB immunotherapy for cancer treatment.
Clinical exome sequencing data reveal high diagnostic yields for congenital diaphragmatic hernia plus (CDH+) and new phenotypic expansions involving CDH
Authors: Scott Tiana M , Campbell Ian M , Hernandez-Garcia Andres , Lalani Seema R , Liu Pengfei , Shaw Chad A , Rosenfeld Jill A , Scott Daryl A 
Published: January 2021

BackgroundCongenital diaphragmatic hernia (CDH) is a life-threatening birth defect that often co-occurs with non-hernia-related anomalies (CDH+). While copy number variant (CNV) analysis is often employed as a diagnostic test for CDH+, clinical exome sequencing (ES) has not been universally adopted.MethodsWe analysed a clinical database of ~12 000 test results to determine the diagnostic yields of ES in CDH+ and to identify new phenotypic expansions.ResultsAmong the 76 cases with an indication of CDH+, a molecular diagnosis was made in 28 cases for a diagnostic yield of 37% (28/76). A provisional diagnosis was made in seven other cases (9%; 7/76). Four individuals had a diagnosis of Kabuki syndrome caused by frameshift variants inKMT2D. Putatively deleterious variants inALG12andEP300were each found in two individuals, supporting their role in CDH development. We also identified individuals with de novo pathogenic variants inFOXP1andSMARCA4, and compound heterozygous pathogenic variants inBRCA2. The role of these genes in CDH development is supported by the expression of their mouse homologs in the developing diaphragm, their high CDH-specific pathogenicity scores generated using a previously validated algorithm for genome-scale knowledge synthesis and previously published case reports.ConclusionWe conclude that ES should be ordered in cases of CDH+ when a specific diagnosis is not suspected and CNV analyses are negative. Our results also provide evidence in favour of phenotypic expansions involving CDH for genes associated withALG12-congenital disorder of glycosylation, Rubinstein-Taybi syndrome, Fanconi anaemia, Coffin-Siris syndrome andFOXP1-related disorders.
CHARGE-AF in a national routine primary care electronic health records database in the Netherlands: validation for 5-year risk of atrial fibrillation and implications for patient selection in atrial fibrillation screening
Authors: Himmelreich Jelle C L , Lucassen Wim A M , Harskamp Ralf E , Aussems Claire , van Weert Henk C P M , Nielen Mark M J 
Published: January 2021

AimsTo validate a multivariable risk prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology model for atrial fibrillation (CHARGE-AF)) for 5-year risk of atrial fibrillation (AF) in routinely collected primary care data and to assess CHARGE-AF’s potential for automated, low-cost selection of patients at high risk for AF based on routine primary care data.MethodsWe included patients aged ≥40 years, free of AF and with complete CHARGE-AF variables at baseline, 1 January 2014, in a representative, nationwide routine primary care database in the Netherlands (Nivel-PCD). We validated CHARGE-AF for 5-year observed AF incidence using the C-statistic for discrimination, and calibration plot and stratified Kaplan-Meier plot for calibration. We compared CHARGE-AF with other predictors and assessed implications of using different CHARGE-AF cut-offs to select high-risk patients.ResultsAmong 111 475 patients free of AF and with complete CHARGE-AF variables at baseline (17.2% of all patients aged ≥40 years and free of AF), mean age was 65.5 years, and 53% were female. Complete CHARGE-AF cases were older and had higher AF incidence and cardiovascular comorbidity rate than incomplete cases. There were 5264 (4.7%) new AF cases during 5-year follow-up among complete cases. CHARGE-AF’s C-statistic for new AF was 0.74 (95% CI 0.73 to 0.74). The calibration plot showed slight risk underestimation in low-risk deciles and overestimation of absolute AF risk in those with highest predicted risk. The Kaplan-Meier plot with categories <2.5%, 2.5%–5% and >5% predicted 5-year risk was highly accurate. CHARGE-AF outperformed CHA2DS2-VASc (Cardiac failure or dysfunction, Hypertension, Age >=75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [Female]) and age alone as predictors for AF. Dichotomisation at cut-offs of 2.5%, 5% and 10% baseline CHARGE-AF risk all showed merits for patient selection in AF screening efforts.ConclusionIn patients with complete baseline CHARGE-AF data through routine Dutch primary care, CHARGE-AF accurately assessed AF risk among older primary care patients, outperformed both CHA2DS2-VASc and age alone as predictors for AF and showed potential for automated, low-cost patient selection in AF screening.
Impaired coronary flow velocity reserve is associated with cardiovascular risk factors but not with angina symptoms
Authors: Bove Kira Bang , Michelsen Marie M , Schroder Jakob , Suhrs Hannah Elena , Bechsgaard Daria F , Mygind Naja Dam , Aziz Ahmed , Kastrup Jens , Gustafsson Ida , Prescott Eva 
Published: January 2021

ObjectivesCoronary microvascular dysfunction (CMD) is considered to cause angina pectoris in a large proportion of women with no obstructive coronary artery disease (CAD). However, data supporting a relation between angina pectoris and CMD are limited. We compared CMD in women with angina with asymptomatic women and evaluated the relation between presence of CMD, angina characteristics, cardiovascular risk factors and results of stress testing.MethodsIn a cross-sectional study, we included 1684 women with angina and <50% coronary artery stenosis on invasive angiography. Asymptomatic women from the community-based Copenhagen City Heart Study served as reference group (n=102). Coronary microvascular function was determined by coronary flow velocity reserve (CFVR) assessed by transthoracic Doppler stress echocardiography. CFVR < 2 was defined as CMD. Symptoms were obtained from standardised angina questionnaires and results of stress testing from health records.ResultsMedian CFVR was 2.33 (IQR 2.00–2.75) in symptomatic women versus 2.60 (2.19–2.95) in asymptomatic (p=0.007). CFVR <2 was found in 25% of symptomatic and in 19% of asymptomatic women. Symptomatic women had a greater risk factor burden. After adjusting for age, hypertension, diabetes, smoking and heart rate the difference in CFVR between groups disappeared (p=0.213). We found no associations between CFVR and angina characteristics, symptom burden or results from stress testing.ConclusionsImpaired CFVR is more prevalent in symptomatic than in asymptomatic women and related to the cardiovascular risk factors hypertension, diabetes, smoking and increased heart rate. Neither a positive bicycle test, single photon emission CT stress test nor chest pain characteristics identify women with impaired CFVR among women with angina and no obstructive CAD. Results may question the concept of microvascular angina as currently defined.
Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study
Authors: López-Medina Clementina , Molto Anna , Sieper Joachim , Duruöz Tuncay , Kiltz Uta , Elzorkany Bassel , Hajjaj-Hassouni Najia , Burgos-Vargas Ruben , Maldonado-Cocco José , Ziade Nelly , Gavali Meghna , Navarro-Compan Victoria , Luo Shue-Fen , Monti Sara , Tae-Jong Kim , Kishimoto Mitsumasa , Pimentel-Santos F M , Gu Jieruo , Schiotis Ruxandra , van Gaalen Floris A , Geher Pál , Magrey Marina , Ibáñez Vodnizza Sebastián E , Bautista-Molano Wilson , Maksymowych Walter , Machado Pedro M , Landewé Robert , van der Heijde Desirée , Dougados Maxime 
Published: January 2021

ObjectivesTo characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.MethodsCross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.ResultsA total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).ConclusionThese results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.
COVID-19 restrictions and changing sexual behaviours in HIV-negative MSM at high risk of HIV infection in London, UK
Authors: Hyndman Iain , Nugent Diarmuid , Whitlock Gary George , McOwan Alan , Girometti Nicolò 
Published: January 2021

ObjectivesThe COVID-19 pandemic and its related restrictions have affected attendance to and delivery of UK sexual healthcare services (SHS). We surveyed the impact on sexual behaviour of men having sex with men (MSM) to inform future SHS provision.MethodsWe conducted a cross-sectional, anonymous, web-based survey among HIV-negative MSM at high risk of HIV infection who attended 56 Dean Street, a sexual health and HIV clinic. The survey was conducted over a 7-day period in August 2020. Data on sociodemographic characteristics, sexual behaviour and related mental well-being experienced during lockdown (defined as 23 March–30 June 2020) were extracted. Categorical and non-categorical variables were compared according to HIV pre-exposure prophylaxis (PrEP) use.Results814 MSM completed the questionnaire: 75% were PrEP users; 76% reported they have been sexually active, of which 76% reported sex outside their household. 75% reported fewer partners than prior to lockdown. Isolation/loneliness (48%) and anxiety/stress (27%) triggered sexual activity, and 73% had discussed COVID-19 transmission risks with their sexual partners. While 46% reported no change to emotions ordinarily experienced following sex, 20% reported guilt for breaching COVID-19 restrictions. 76% implemented one or more changes to their sexual behaviour, while 58% applied one or more steps to reduce COVID-19 transmission during sex. 36% accessed SHS and 30% reported difficulties in accessing testing/treatment. Of those who accessed SHS, 28% reported an STI diagnosis. PrEP users reported higher partner number, engagement in ‘chemsex’ and use of SHS than non-PrEP users.ConclusionsCOVID-19 restrictions had a considerable impact on sexual behaviour and mental well-being in our survey respondents. High rates of sexual activity and STI diagnoses were reported during lockdown. Changes to SHS provision for MSM must respond to high rates of psychological and STI-related morbidity and the challenges faced by this population in accessing services.
Phase transition and entropic force of de Sitter black hole in massive gravity
Authors: Ma Yubo , Zhang Yang , Zhang Lichun , Wu Liang , Gao Ying , Cao Shuo , Pan Yu 
Published: January 2021

AbstractIt is well known that de Sitter(dS) black holes generally have a black hole horizon and a cosmological horizon, both of which have Hawking radiation. But the radiation temperature of the two horizons is generally different, so dS black holes do not meet the requirements of thermal equilibrium stability, which brings certain difficulties to the study of the thermodynamic characteristics of black holes. In this paper, dS black hole is regarded as a thermodynamic system, and the effective thermodynamic quantities of the system are obtained. The influence of various state parameters on the effective thermodynamic quantities in the massive gravity space-time is discussed. The condition of the phase transition of the de Sitter black hole in massive gravity space-time is given. We consider that the total entropy of the dS black hole is the sum of the corresponding entropy of the two horizons plus an extra term from the correlation of the two horizons. By comparing the entropic force of interaction between black hole horizon and the cosmological horizon with Lennard-Jones force between two particles, we find that the change rule of entropic force between the two system is surprisingly the same. The research will help us to explore the real reason of accelerating expansion of the universe.
Parameter-free description of the manifold of non-degenerate density matrices
Authors: Naudts Jan 
Published: January 2021

AbstractThe paper gives a definition of exponential arcs in the manifold of non-degenerate density matrices and uses it as a starting point to develop a parameter-free version of non-commutative Information Geometry in the finite-dimensional case. Given the Bogoliubov metric, the m- and e-connections are each other dual. Convex potentials are introduced. They allow to introduce dual charts. Affine coordinates are introduced at the end to make the connection with the more usual approach.