bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19)
Authors: Zhu Rui-fang , Gao Yu-lu , Robert Sue-Ho , Gao Jin-ping , Yang Shi-gui , Zhu Chang-tai 
Published: July 2020

Abstract
Background
Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics.

Methods
This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias.

Results
A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60–200), and the median length of the trial periods was 179 d (IQR: 94–366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low.

Conclusions
Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.
SOPEZ: study for the optimization of ergonomics in the dental practice - musculoskeletal disorders in dentists and dental assistants: a study protocol
Authors: Ohlendorf Daniela , Maltry Laura , Hänel Jasmin , Betz Werner , Erbe Christina , Maurer-Grubinger Christian , Holzgreve Fabian , Wanke Eileen M. , Brüggmann Dörthe , Nienhaus Albert , Groneberg David A. 
Published: July 2020

Abstract
Background
Musculoskeletal disorders (MSD) are common among dental professionals. The most common areas affected are the trunk, neck, shoulders and wrists. Current evidence suggests that the causes of MSD can be found in the physical demands of the profession. Posture and movement during treatment is influenced by the arrangement of the treatment concept (patient chair, equipment and cabinets). It has not been investigated whether the ergonomic risk differs between the treatment concepts.

Methods
To evaluate the prevalence of MSD in dental professionals, 1000 responses will be collected from a nationwide (Germany) online questionnaire (mod. Nordic Questionnaire and mod. Meyer questionnaire). In order to assess the ergonomic risk of the treatment techniques used in the four treatment concepts, 3D movement analyses are carried out with inertial sensors. For this purpose, 20 teams of dentists and dental assistants from four dental fields of specializations (generalists, orthodontists, endodontists and oral surgeons) and a student control group will be recruited. Each team will execute field specific standardized treatments at a dummy head. Measurements are carried out in each of the four treatment concepts. The data will be analyzed using the Rapid Upper Limb Assessment (RULA) which will be modified for the evaluation of objective data.

Conclusions
On the basis of these investigations, a substantial gain of knowledge regarding work-related MSD in the field of dentistry and its potential biomechanical causes is possible. For the first time, objective and differentiated comparisons between the four treatment concepts are possible for different fields of dental specialization. Up to now, statically held positions of the trunk and proximal upper extremities, but also the repetitive movements of the hands have been considered a risk for MSD. Since both are included in the RULA, dental activities can be assessed in a detailed but also global manner with regard to ergonomic risks.
Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity
Authors: Darshana Thamal , Bandara Dayananda , Nawarathne Upul , de Silva Udaya , Costa Yasinta , Pushpakumara Kalavitigoda , Pathirage Sumithra , Basnayake Seuwandi , Epa Chamila , Dilrukshi Pradeepa , Wijayawardena Maheshaka , Anthony Angela A. , Rodrigo Rexan , Manamperi Aresha , Smith Frances , Allen Angela , Menzel Stephan , Rees David , Premawardhena Anuja 
Published: July 2020

Abstract
Background
Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this “rare” group of patients.

Results
All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016–March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04).

Conclusions
Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.
Constructing an automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning
Authors: Kong Yanguo , Kong Xiangyi , He Cheng , Liu Changsong , Wang Liting , Su Lijuan , Gao Jun , Guo Qi , Cheng Ran 
Published: July 2020

AbstractDue to acromegaly’s insidious onset and slow progression, its diagnosis is usually delayed, thus causing severe complications and treatment difficulty. A convenient screening method is imperative. Based on our previous work, we herein developed a new automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning on the data of 2148 photographs at different severity levels. Each photograph was given a score reflecting its severity (range 1~3). Our developed model achieved a prediction accuracy of 90.7% on the internal test dataset and outperformed the performance of ten junior internal medicine physicians (89.0%). The prospect of applying this model to real clinical practices is promising due to its potential health economic benefits.
Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression
Authors: Xia Chenglai , Liu Chang , He Zhihong , Cai Yantao , Chen Jinman 
Published: July 2020

AbstractBackgroundRecent studies have shown that the classic hypoglycemic drug metformin inhibits tumor growth; however, the underlying mechanism remains unclear. We previously showed that metformin disrupts the sponge effect of long non-coding RNA MALAT1/miR-142-3p to inhibit cervical cancer cell proliferation. In this study, we interrogated the ability of metformin to modulate the anti-tumor immune response in cervical cancer.MethodsThe cell counting kit-8 assay was used to detect the viability of cervical cancer cells. Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Lactate dehydrogenase (LDH) cytotoxicity assay was used to detect NK Cell Cytotoxicity. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of metformin in vivo.ResultsMetformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt. Moreover metformin induced cervical cancer cell apoptosis and caused cancer cell cycle arrest. In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells. Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity.ConclusionsIn conclusion, our results suggest that metformin may be used as immunopotentiator to inhibit cervical cancer progression and may be considered a viable candidate for combination therapy with immunotherapy.
Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma
Authors: Feng Jiao , Li Jingjing , Wu Liwei , Yu Qiang , Ji Jie , Wu Jianye , Dai Weiqi , Guo Chuanyong 
Published: July 2020

AbstractLiver cancer has become the sixth most diagnosed cancer and the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is responsible for up to 75–85% of primary liver cancers, and sorafenib is the first targeted drug for advanced HCC treatment. However, sorafenib resistance is common because of the resultant enhancement of aerobic glycolysis and other molecular mechanisms. Aerobic glycolysis was firstly found in HCC, acts as a hallmark of liver cancer and is responsible for the regulation of proliferation, immune evasion, invasion, metastasis, angiogenesis, and drug resistance in HCC. The three rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), and pyruvate kinases type M2 (PKM2) play an important role in the regulation of aerobic glycolysis in HCC and can be regulated by many mechanisms, such as the AMPK, PI3K/Akt pathway, HIF-1α, c-Myc and noncoding RNAs. Because of the importance of aerobic glycolysis in the progression of HCC, targeting key factors in its pathway such as the inhibition of HK2, PFK or PKM2, represent potential new therapeutic approaches for the treatment of HCC.
Targeted re-sequencing for early diagnosis of genetic causes of childhood epilepsy: the Italian experience from the ‘beyond epilepsy’ project
Authors: Amadori Elisabetta , Scala Marcello , Cereda Giulia Sofia , Vari Maria Stella , Marchese Francesca , Di Pisa Veronica , Mancardi Maria Margherita , Giacomini Thea , Siri Laura , Vercellino Fabiana , Serino Domenico , Orsini Alessandro , Bonuccelli Alice , Bagnasco Irene , Papa Amanda , Minetti Carlo , Cordelli Duccio Maria , Striano Pasquale 
Published: July 2020

Abstract
Background
Childhood epilepsies are a heterogeneous group of conditions differing in diagnostic criteria, management, and outcome. Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative condition caused by biallelic TPP1 variants. This disorder presents with subtle and relatively non-specific symptoms, mimicking those observed in more common paediatric epilepsies and followed by rapid psychomotor deterioration and drug-resistant epilepsy. A prompt diagnosis is essential to adopt appropriate treatment and disease management strategies.

Methods
This is a prospective, multicentre study on the efficiency of targeted re-sequencing in the early identification of the genetic causes of childhood epilepsy, with particular regard to CLN2. After phenotypic characterization, a 283-gene Next Generation Sequencing panel was performed in 21 Italian children with neurodevelopmental abnormalities, aged between 24 and 60 months, experiencing first unprovoked seizure after 2 years of age.

Results
The average age at enrolment was 39.9 months, with a mean age at seizure onset of 30.9 months and a mean time interval between seizure onset and targeted resequencing of 9 months. Genetic confirmation was achieved in 4 out of 21 patients, with a diagnostic yield of 19%. In one case, the homozygous splice acceptor variant c.509-1G > C in TPP1 was identified, leading to a CLN2 diagnosis. Three pathogenic variants in MECP2 were also detected in three patients, including the frameshift variant c.1157_1186delinsA (p.Leu386Hisfs*9) in a girl with negative single gene sequencing. Variants of unknown significance (VUS) were found in 11 out of 21 (52.4%) individuals, whereas no clinically significant variants were observed in the remaining 6 subjects.

Conclusions
Our findings support the efficacy of target re-sequencing in the identification of the genetic causes of childhood epilepsy and suggest that this technique might prove successful in the early detection of CLN2 as well as other neurodevelopmental conditions.
Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease
Authors: Rastad Hadith , Karim Hossein , Ejtahed Hanieh-Sadat , Tajbakhsh Ramin , Noorisepehr Mohammad , Babaei Mehrdad , Azimzadeh Mehdi , Soleimani Alireza , Inanloo Seyed Hasan , Shafiabadi Hassani Neda , Rasanezhad Fariba , Shahrestanaki Ehsan , Khodaparast Zeinab , Golami Hossein , Qorbani Mostafa 
Published: July 2020

AbstractBackgroundDiabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD.MethodsThis retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities.ResultsAmong 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14–2.30)) and only DM (1.69 (1.05–2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19(OR: 2.66 (95% CI 2.09–3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05).ConclusionsOur findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.
Transposable elements in Drosophila
Authors: Mérel Vincent , Boulesteix Matthieu , Fablet Marie , Vieira Cristina 
Published: July 2020

AbstractDrosophila has been studied as a biological model for many years and many discoveries in biology rely on this species. Research on transposable elements (TEs) is not an exception. Drosophila has contributed significantly to our knowledge on the mechanisms of transposition and their regulation, but above all, it was one of the first organisms on which genetic and genomic studies of populations were done. In this review article, in a very broad way, we will approach the TEs of Drosophila with a historical hindsight as well as recent discoveries in the field.
Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique
Authors: Mohamed Aziza K. , Elhassan Nazik M. , Awhag Zahra A. , Ali Fadwa S. , Ali Eman T. , Mhmoud Najwa A. , Siddig Emmanuel E. , Hassan Rowa , Ahmed Eiman S. , Fattahi Azam , Ahmed Ayman , Muneer Mohamed S. , Osman Hussam A. , Mohamed Nouh S. , Edris Ali M. M. 
Published: July 2020

Abstract
Objectives
Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique.

Results
Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.
Scintigraphy evaluation of hyperthyroidism and its correlation with clinical and biochemical profiles
Authors: Alswat Khaled , Assiri Sara Ahmad , Althaqafi Raad M. M. , Alsufyani Atheer , Althagafi Abaad , Alrebaiee Sara , Alsukhayri Najd 
Published: July 2020

Abstract
Objective
Hyperthyroidism is the excessive synthesis of thyroid hormones. Thyroid uptake scans and ultrasonography provide an accurate diagnosis of hyperthyroidism, especially when thyroid receptor antibody (TRAb) measurement is not readily available. This study explored the prevalence of various hyperthyroidism causes using retrospective scintigraphy results and evaluated their relationship with clinical, biochemical, and sonographic imaging parameters from patients who underwent 99mTc-pertechnetate thyroid scans between 2016 and 2019 in Taif, Saudi Arabia, where literature is insufficient. Furthermore, the inappropriate use of thyroid scanning in different thyroid diseases was evaluated.

Results
The study enrolled 207 patients (mean age: 42.5 ± 14.7 years). The mean free T4, T3, antithyroid peroxidase antibody, antithyroglobulin antibody, C-reactive protein, and erythrocyte sedimentation rate levels were high. Graves’ disease was the most common diagnosis. Compared to toxic solitary/multinodular goiter, patients with Graves’ disease were usually younger, used carbimazole during both the uptake and the scan, had an enlarged thyroid gland, and had higher FT4 and FT3 levels. Inappropriate thyroid uptake and scan use was reported in approximately 10% of patients, and 25% of the patients used carbimazole during the uptake and scan. Thus, better patient education is needed to avoid misinterpreting the scan results.
Enzymatic activity and brine shrimp lethality of venom from the large brown spitting cobra (Naja ashei) and its neutralization by antivenom
Authors: Okumu Mitchel Otieno , Mbaria James Mucunu , Gikunju Joseph Kangangi , Mbuthia Paul Gichohi , Madadi Vincent Odongo , Ochola Francis Okumu 
Published: July 2020

AbstractObjectiveNaja asheiis a snake of medical importance in Kenya, Ethiopia, Somalia, Uganda, and Tanzania. Little is known about the enzymatic (snake venom phospholipases A2; svPLA2’s) and toxic (lethal) activities ofN. asheivenom and crucially, the safety and capacity of available antivenom to neutralize these effects. This study aimed to determine the enzymatic and toxic activities ofN. asheivenom and the capacity of Indian and Mexican manufactured antivenoms to neutralize these effects. The protein content of the venom and the test antivenoms were also evaluated. A 12-point log concentration–response curve (0.5–22.5 µg/mL) was generated on an agarose-egg yolk model to predict the svPLA2activity of the venom. The toxicity profiles of the venom and antivenoms were evaluated in the brine shrimp lethality assay. Lowry’s method was used for protein estimation.ResultsLow and intermediate concentrations of the venom exhibited similar svPLA2activities. The same was true for concentrations > 15 µg/mL. Intermediate and high doses of the venom exhibited similar mortalities in brine shrimp and test antivenoms were generally non-toxic but poorly neutralized svPLA2activity. Mexican manufactured antivenom had lower protein content but neutralized venom-induced brine shrimp lethality much more effectively than Indian manufactured antivenom.
Current status of development of methylation biomarkers for in vitro diagnostic IVD applications
Authors: Taryma-Leśniak Olga , Sokolowska Katarzyna Ewa , Wojdacz Tomasz Kazimierz 
Published: July 2020

AbstractA significant volume of research clearly shows that disease-related methylation changes can be used as biomarkers at all stages of clinical disease management, including risk assessment and predisposition screening through early diagnostics to personalization of patient care and monitoring of the relapse and chronic disease. Thus disease-related methylation changes are an attractive source of the biomarkers that can have significant impact on precision medicine. However, the translation of the research findings in methylation biomarkers field to clinical practice is at the very least not satisfactory. That is mainly because the evidence generated in research studies indicating the utility of the disease-related methylation change to predict clinical outcome is in majority of the cases not sufficient to postulate the diagnostic use of the biomarker. The research studies need to be followed by well-designed and systematic investigations of clinical utility of the biomarker that produce data of sufficient quality to meet regulatory approval for the test to be used to make clinically valid decision. In this review, we describe methylation-based IVD tests currently approved for IVD use or at the advanced stages of the development for the diagnostic use. For each of those tests, we analyze the technologies that the test utilizes for methylation detection as well as describe the types of the clinical studies that were performed to show clinical validity of the test and warrant regulatory approval. The examples reviewed here should help with planning of clinical investigations and delivery of the clinical evidence required for the regulatory approval of potential methylation biomarker based IVD tests.