bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of highversuslow dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 pneumonia: an open-label, randomised clinical trial
Authors: Taboada Manuel , Rodríguez Nuria , Varela Pablo Manuel , Rodríguez María Teresa , Abelleira Romina , González Amara , Casal Ana , Díaz Peromingo José Antonio , Lama Adriana , Domínguez María Jesús , Rábade Carlos , Páez Emilio Manuel , Riveiro Vanessa , Pernas Hadrián , Beceiro María del Carmen , Caruezo Valentín , Naveira Alberto , Cariñena Agustín , Cabaleiro Teresa , Estany-Gestal Ana , Zarra Irene , Pose Antonio , Valdés Luis , Álvarez-Escudero Julián 
Published: December 2021

BackgroundLow-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean±sdage 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.
Imprinting of bronchial epithelial cells uponin vivorhinovirus infection in people with asthma
Authors: Ravi Abilash , Chowdhury Saheli , Dijkhuis Annemiek , Dierdorp Barbara S. , Dekker Tamara , Kruize Rianne , Sabogal Piñeros Yanaika S. , Majoor Christof J. , Sterk Peter J. , Lutter René 
Published: December 2021

BackgroundDefective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed uponin vivoexposure to rhinovirus (RV)-A16 and applies to the bronchoconstrictor endothelin-1.MethodsBECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post-RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness.ResultsEpithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals.In vitroCXCL-8 and endothelin-1 production correlated.In vivorelevance forin vitroCXCL-8 and endothelin-1 production was shown by correlations with forced expiratory volume in 1 s % predicted and CXCL-8 BALF levels.ConclusionEpithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.
Genome-wide identification of enhancers and transcription factors regulating the myogenic differentiation of bovine satellite cells
Authors: Lyu Pengcheng , Settlage Robert E. , Jiang Honglin 
Published: December 2021

AbstractBackgroundSatellite cells are the myogenic precursor cells in adult skeletal muscle. The objective of this study was to identify enhancers and transcription factors that regulate gene expression during the differentiation of bovine satellite cells into myotubes.ResultsChromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to identify genomic regions where lysine 27 of H3 histone is acetylated (H3K27ac), i.e., active enhancers, from bovine satellite cells before and during differentiation into myotubes. A total of 19,027 and 47,669 H3K27ac-marked enhancers were consistently identified from two biological replicates of before- and during-differentiation bovine satellite cells, respectively. Of these enhancers, 5882 were specific to before-differentiation, 35,723 to during-differentiation, and 13,199 common to before- and during-differentiation bovine satellite cells. Whereas most of the before- or during-differentiation-specific H3K27ac-marked enhancers were located distally to the transcription start site, the enhancers common to before- and during-differentiation were located both distally and proximally to the transcription start site. The three sets of H3K27ac-marked enhancers were associated with functionally different genes and enriched with different transcription factor binding sites. Specifically, many of the H3K27ac-marked enhancers specific to during-differentiation bovine satellite cells were associated with genes involved in muscle structure and development, and were enriched with binding sites for the MyoD, AP-1, KLF, TEAD, and MEF2 families of transcription factors. A positive role was validated for Fos and FosB, two AP-1 family transcription factors, in the differentiation of bovine satellite cells into myotubes by siRNA-mediated knockdown.ConclusionsTens of thousands of H3K27ac-marked active enhancers have been identified from bovine satellite cells before or during differentiation. These enhancers contain binding sites not only for transcription factors whose role in satellite cell differentiation is well known but also for transcription factors whose role in satellite cell differentiation is unknown. These enhancers and transcription factors are valuable resources for understanding the complex mechanism that mediates gene expression during satellite cell differentiation. Because satellite cell differentiation is a key step in skeletal muscle growth, the enhancers, the transcription factors, and their target genes identified in this study are also valuable resources for identifying and interpreting skeletal muscle trait-associated DNA variants in cattle.
Spectrum of cardiovascular diseases at a referral tertiary care hospital in Somalia, Mogadishu: an echocardiographic study
Authors: Alıcı Gökhan , Genç Ömer 
Published: December 2021

Abstract
Background
To investigate the frequencies and patterns of cardiovascular diseases (CVDs), including rheumatic and congenital heart diseases, among patients with abnormal hearts assessed by echocardiographic examination.

Methods
This retrospective, descriptive registry reviewed abnormal echocardiographic findings of 1140 patients aged 0–100 years who were admitted to the cardiology outpatient clinic at a tertiary training institution in Mogadishu.

Results
Hypertensive heart disease (HHD) (n:454, 39.8%), valvular heart disease (VHD) (n:395, 34.6%),
and heart failure with reduced ejection fraction (HFrEF) (n:351, 30.8%) were the most frequent comorbidities. Congenital heart diseases (CHDs) were detected in 151 (13.2%) of the patients, with the most common ones including atrial septal defect (ASD) (n:37, 3.2%) and ventricular septal defect (VSD) (n:26, 2.3%). Rheumatic heart disease (RHD) was observed in 84 (7.4%) patients, among whom the most common age range was 16–30 years (40.5%), followed by 31–45 years (31%) and 0–15 years (15.5%). Mitral insufficiency (n:541, 47.5%) was detected as the most frequent VHD, followed by aortic insufficiency (n:437, 38.3%), and tricuspid insufficiency (n:264, 23.2%) and mitral valve stenosis (n:39, 3.4%) was the least common VHD.

Conclusion
In the present study, we found that HHD was the most common comorbidity, followed by VHD, and HFrEF. Moreover, the most common VHD was mitral insufficiency and the most common CHD was ASD.
Willingness, beliefs, and barriers regarding the COVID-19 vaccine in Saudi Arabia: a multiregional cross-sectional study
Authors: Altulahi Noura , AlNujaim Shouq , Alabdulqader Azzam , Alkharashi Abdullah , AlMalki Assaf , AlSiari Faisal , Bashawri Yara , Alsubaie Sarah , AlShahrani Dayel , AlGoraini Yara 
Published: December 2021

Abstract
Background
The coronavirus disease 2019 (COVID-19) has spread worldwide, and the vaccine remains the ultimate cornerstone to overcoming its long-term impact. Vaccine hesitancy might obstruct the effort to achieve herd immunity and eradicate the virus. We assessed Saudi Arabian individuals’ willingness, beliefs, and barriers regarding the COVID-19 vaccine and their adherence to preventive measures during and after the pandemic.

Methods
A self-administered electronic validated questionnaire was distributed among the five major regions in Saudi Arabia between November and December 2020. The questionnaire addressed the sociodemographic data, beliefs, potential barriers, parents’ acceptance of COVID-19 vaccination for their children, and adherence to protective measures during and after the pandemic.

Results
Of 8,056 participants, 4,218 (52.4%) of a non-representative sample were willing to be vaccinated against COVID-19. Being a young adult, male, having less than a high school degree, being a smoker, having a chronic disease, and having a history of seasonal influenza vaccine uptake were positive predictors of COVID-19 vaccine acceptance. Hesitant participants reported concerns about vaccine side effects and safety as the main barriers to accepting the COVID-19 vaccine. Some refusers (26.1%) declared that they would reconsider vaccination only if the safety and effectiveness of the vaccine were reported by more studies.

Conclusions
Our study revealed a promising willingness to accept the vaccine among the population, with positive beliefs and attitudes toward COVID-19 vaccination. However, a considerable proportion of the population was reluctant to accept the vaccine. Thus, publicly providing information about vaccine safety and implementing health education programs is crucial for increasing the public’s confidence in the vaccine.
IRF4-activated TEX41 promotes the malignant behaviors of melanoma cells by targeting miR-103a-3p/C1QB axis
Authors: Zheng Yingna , Zhou Wu , Li Min , Xu Ruixue , Zhang Shuai , Liu Ying , Cen Ying 
Published: December 2021

Abstract
Background
Malignant melanoma is an aggressive skin cancer and a tumor of melanocytic origin. Recent studies have suggested that long non-coding RNAs (lncRNAs) play crucial regulatory roles in multiple malignancies, including melanoma. Testis expressed 41 (TEX41) is a relatively new lncRNA whose mechanism in melanoma remains vague.

Aims
This study aimed to explore the role and specific mechanism of TEX41 in melanoma.

Methods
The expression of genes involved in this study was determined by qRT-PCR. Functional assays were conducted to analyze the role of relevant genes in melanoma cells. The interaction between TEX41 promoter and IRF4 as well as the relationship among TEX41, miR-103a-3p and C1QB was verified by mechanism assays.

Results
IRF4 up-regulated TEX41 at the transcriptional level in melanoma cells. TEX41 knockdown hindered melanoma cell proliferation, migration and invasion while promoting cell apoptosis. TEX41 bound to miR-103a-3p and regulated C1QB. The suppressive impact of TEX41 depletion on melanoma cell malignant behaviors could be counteracted by miR-103a-3p inhibition or C1QB overexpression. Moreover, IRF4 could facilitate melanoma cell growth via up-regulating C1QB.

Conclusions
IRF4-activated TEX41 sequestered miR-103a-3p and modulated C1QB to promote melanoma cell malignant behaviors, for which TEX41 might be regarded as a potential therapeutic target for melanoma.
Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report
Authors: Brennerová Katarína , Škopková Martina , Ostrožlíková Mária , Šaligová Jana , Staník Juraj , Bzdúch Vladimír , Gašperíková Daniela 
Published: December 2021

Abstract
Background
Isolated methylmalonic aciduria can be caused by pathogenic mutations in the gene for methylmalonyl-CoA mutase or in the genes encoding enzymes involved in the intracellular metabolism of cobalamin. Some of these mutations may be cobalamin responsive. The type of methylmalonic aciduria cannot always be assumed from clinical manifestation and the responsiveness to cobalamin has to be assessed for appropriate cobalamin administration, or to avoid unnecessary treatment. The cases presented herein highlight the importance of genetic testing in methylmalonic aciduria cases and the need for standardisation of the in vivo cobalamin-responsiveness assessment.

Case presentation
We describe two patients who presented in the first week of life with rapid neurological deterioration caused by metabolic acidosis with severe hyperammonaemia requiring extracorporeal elimination in addition to protein restriction, energy support, carnitine, and vitamin B12 treatment. The severity of the clinical symptoms and high methylmalonic acid concentrations in the urine (>30,000 μmol/mmol of creatinine) without hyperhomocysteinaemia in both of our patients suggested isolated methylmalonic aciduria. Based on the neonatal manifestation and the high methylmalonic acid urine levels, we assumed the cobalamin non-responsive form. The in vivo test of responsiveness to cobalamin was performed in both patients. Patient 1 was evaluated as non-responsive; thus, intensive treatment with vitamin B12 was not used. Patient 2 was responsive to cobalamin, but the dose was decreased to 1 mg i.m. every two weeks with daily oral treatment due to non-compliance. Genetic tests revealed bi-allelic mutations in the genes MMAB and MMAA in Patient 1 and 2, respectively. Based on these results, we were able to start intensive treatment with hydroxocobalamin in both patients. After the treatment intensification, there was no acute crisis requiring hospitalisation in Patient 1, and the urine methylmalonic acid levels further decreased in Patient 2.

Conclusions
Despite carrying out the in vivo test of responsiveness to cobalamin in both patients, only the results of molecular genetic tests led us to the correct diagnosis and enabled intensive treatment with hydroxocobalamin. The combination of the standardized in vivo test of cobalamin responsiveness and genetic testing is needed for accurate diagnosis and appropriate treatment of isolated methylmalonic aciduria.
The effect of PLISSIT based counseling model on sexual function, quality of life, and sexual distress in women surviving breast cancer: a single-group pretest–posttest trial
Authors: Keshavarz Zohreh , Karimi Elham , Golezar Samira , Ozgoli Giti , Nasiri Maliheh 
Published: December 2021

Abstract
Background
Diagnosis and treatment of breast cancer potentially leads to sexual dysfunction and sexual distress in women and negatively affects their quality of life (QoL). This study aimed at determining the effect of PLISSIT based counseling on sexual function, sexual distress, and QoL in women surviving breast cancer.

Methods
In this pre-test, post-test, single-group semi-experimental study, 65 women surviving breast cancer who were referred to the selected centers were included in the study via the available sampling method. Data gathering tools included a researcher-made demographic questionnaire, female sexual function index, beck depression inventory-II, State‐Trait Anxiety Inventory, World Health Organization QoL-Brief, and Female Sexual Distress Scale-Revised. The counseling program (7 sessions 60 min each) was designed based on the PLISSIT model. The sexual function, sexual distress, and QoL were evaluated before, and 2 and 4 weeks after the intervention. To compare the mean scores of variables before and after the intervention, repeated-measured ANOVA was used.

Results
The findings showed that PLISSIT based counseling significantly reduced sexual distress and increased the scores of QoL and all its domains, as well as sexual function and all its domains in women surviving breast cancer (p < 0.05). There was no significant difference in the mean scores of variables 2 and 4 weeks after the intervention.

Conclusions
It seems that PLISSIT based counseling reduces sexual dysfunction and sexual distress and improves the QoL of women surviving breast cancer. So, it is recommended that these counseling programs be integrated into the health care program of this group of women.

Trial registration

TCTR202103170010, 17 March 2021, Retrospectively registered, at https://www.thaiclinicaltrials.org/.
SGLT-2 inhibitors and cardiorenal outcomes in patients with or without type 2 diabetes: a meta-analysis of 11 CVOTs
Authors: Giugliano Dario , Longo Miriam , Scappaticcio Lorenzo , Bellastella Giuseppe , Maiorino Maria Ida , Esposito Katherine 
Published: December 2021

Abstract
Background
It has been suggested that sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduce the cardiorenal risk in patients with type 2 diabetes (T2D). The purpose of this study is to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D.

Methods
An electronic search up to 30 September 2021 was conducted in PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. to determine eligible trials. We included CVOTs comparing any SGLT-2 inhibitor with placebo, reporting desired cardiovascular or renal outcomes and with a follow-up duration of at least 6 months.

Results
Eleven CVOTs, with data from five SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) and 77,541 participants, were included. In the overall analysis, the risk of the composite CV mortality or hospitalization for heart failure (HF) was reduced by 23% (HR = 0.77, 95% CI 0.73–0.82, P < 0.001) compared with placebo, with not significant heterogeneity (I2 = 26%, P = 0.20), and irrespective of the presence of T2D (P for interaction = 0.81) and age (> 65 vs ≤ 65 years, P for interaction = 0.78). The risk of CV mortality, total mortality and hospitalization for HF was significantly reduced by 16%, 13%, and 32%, respectively; similarly, the risk of the composite renal outcome was reduced by 35% (HR = 0.65, 95% CI 0.56–0.75), with moderate heterogeneity (I2 = 32%). In the analysis of 6 CVOTs reporting the data, the risk of major cardiovascular events (MACE) was reduced by 12%, with low heterogeneity (I2 = 21.2%, P = 0.19) and irrespective of the presence of established CV disease at baseline (P for interaction = 0.46).

Conclusions
Therapy with SGLT-2 inhibitors in patients with cardiometabolic and renal diseases results in a sustained to moderate reduction of the composite CV death or hospitalization for HF, robust reduction of HF and renal outcomes, moderate reduction of CV mortality, total mortality and MACE.
Insights on functionalized carbon nanotubes for cancer theranostics
Authors: Tang Lu , Xiao Qiaqia , Mei Yijun , He Shun , Zhang Ziyao , Wang Ruotong , Wang Wei 
Published: December 2021

AbstractDespite the exciting breakthroughs in medical technology, cancer still accounts for one of the principle triggers of death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement in cancer therapy with gigantic application potential because of their ability in achieving precise and controlled drug release, elevating drug solubility and reducing adverse effects. Carbon nanotubes (CNTs), one of the most promising carbon-related nanomaterials, have already achieved much success in biomedical field. Due to their excellent optical property, thermal and electronic conductivity, easy functionalization ability and high drug loading capacity, CNTs can be applied in a multifunctional way for cancer treatment and diagnosis. In this review, we will give an overview of the recent progress of CNT-based drug delivery systems in cancer theranostics, which emphasizes their targetability to intracellular components of tumor cells and extracellular elements in tumor microenvironment. Moreover, a detailed introduction on how CNTs penetrate inside the tumor cells to reach their sites of action and achieve the therapeutic effects, as well as their diagnostic applications will be highlighted.
Graphic Abstract
Bilateral actigraphic quantification of upper extremity movement in hemiparetic children with perinatal stroke: a case control study
Authors: Hollis Asha , Cole Lauran , Zewdie Ephrem , Metzler Megan J. , Kirton Adam 
Published: December 2021

Abstract
Background
Hemiparetic cerebral palsy impacts millions of people worldwide. Assessment of bilateral motor function in real life remains a major challenge. We evaluated quantification of upper extremity movement in hemiparetic children using bilateral actigraphy. We hypothesized that movement asymmetry correlates with standard motor outcome measures.

Methods
Hemiparetic and control participants wore bilateral wrist Actiwatch2 (Philips) for 48 h with movement counts recorded in 15-s intervals. The primary outcome was a novel statistic of movement asymmetry, the Actigraphic Movement Asymmetry Index (AMAI). Relationships between AMAI and standard motor outcomes (Assisting Hand Assessment, Melbourne Assessment, and Box and Block Test [BB]) were explored with Pearson or Spearman correlation.

Results
30 stroke (mean 11 years 2 months (3 years 10 months); 13 female, 17 male) and 23 control (mean 11 years 1 month (4 years 5 months); 8 female, 15 male) were enrolled. Stroke participants demonstrated higher asymmetry. Correlations between AMAI and standard tests were moderate and strongest during sleep (BB: r = 0.68, p < 0.01).

Conclusions
Standard tests may not reflect the extent of movement asymmetry during daily life in hemiparetic children. Bilateral actigraphy may be a valuable complementary tool for measuring arm movement, potentially enabling improved evaluation of therapies with a focus on child participation.