bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Audit of Interim Analyses of Randomized Controlled Trials (RCTs)
Published in Three High Impact Factor Medical Journals Over a Seven-
year Period (2012-2018)
Authors: Bose Debdipta , Ravi Renju , Gogtay Nithya , Thatte Urmila M. , Borse Tanvi 
Published: July 2021

Background:
Interim analysis is an integral component of clinical research and drug development
in particular and helps reduce ‘time to market’ for an intervention or stop further development
of unsafe and ineffective interventions. In this audit, we evaluated the extent of use of interim
analyses in published RCTs in three leading journals and their impact on regulatory approval.

Methodology:
RCTs published in JAMA, NEJM and Lancet in the year 2012 to 2018 were extracted.
Each RCT was scrutinized using the filter term ‘Interim’. Both descriptive and inferential statistics
were used to analyze the data. The factors (therapeutic areas, nature of interventions, source of
funding and phases of trials) associated with Interim analysis and its impact on drug approval were
analyzed.

Results:
The majority of RCTs with interim analysis belonged to oncology (27%) and cardiology
(17.2%) and were related to drugs (70%). Majority of the RCTs were in phase 3 (56.3%) and funded
exclusively by Pharmaceutical industry (36.2%). A total of 2% and 14% studies led to accelerated
approval and normal regulatory approval. The choice of alpha spending function was not mentioned
in 44.8% studies and 21% studies used O-Brien Fleming method. A total of 18.5% studies
were stopped early. The oncology trials, drug as intervention and Phase 3 trials were associated
with the conduct of interim analysis which was associated with significantly higher numbers of accelerated
and routine regulatory approvals.

Conclusion:
Majority of the RCTs with interim analysis were from oncology and most did not report
a stopping rule. Interventions that were drugs (rather than devices or surgical procedures). and
phase 3 trials (relative to other phases of RCTs). were associated with significantly higher number
of interim analyses which was also associated with significantly higher number of regulatory approvals.
Six CT83-related Genes-based Prognostic Signature for Lung Adenocarcinoma
Authors: Zhang Guimin , Wang Yongmei , Wang Ruixian 
Published: July 2021

Background:
This study aims to explore the prognostic values of CT83 and CT83-
related genes in lung adenocarcinoma (LUAD).

Methods:
We downloaded the mRNA profiles of 513 LUAD patients (RNA sequencing data) and
246 NSCLC patients (Affymetrix Human Genome U133 Plus 2.0 Array) from TCGA and GEO
databases. According to the median expression of CT83, the TCGA samples were divided into high
and low expression groups, and differential expression analysis between them was performed.
Functional enrichment analysis of differential expression genes (DEGs) was conducted. Univariate
Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal
prognostic DEGs. Then we established the prognostic model. A Nomogram model was constructed
to predict the overall survival (OS) probability of LUAD patients.

Results:
CT83 expression was significantly correlated to the prognosis of LUAD patients. A total
of 59 DEGs were identified, and a predictive model was constructed based on six optimal CT83-
related DEGs, including CPS1, RHOV, TNNT1, FAM83A, IGF2BP1, and GRIN2A, which could
effectively predict the prognosis of LUAD patients. The nomogram could reliably predict the OS
of LUAD patients. Moreover, the six important immune checkpoints (CTLA4, PD1, IDO1, TDO2,
LAG3, and TIGIT) were closely correlated with the risk score, which were also differentially
expressed between the LUAD samples with high and low risk scores, suggesting that the poor
prognosis of LUAD patients with high risk score might be due to the immunosuppressive
microenvironments.

Conclusion:
A prognostic model based on six optimal CT83 related genes could effectively predict
the prognosis of LUAD patients.
Migraine and Obesity: Is There a Relationship? A Systematic Review and Meta-Analysis of Observational Studies
Authors: Hatami Mahsa , Soveid Neda , Lesani Azadeh , Djafarian Kurosh , Shab-Bidar Sakineh 
Published: July 2021

Background and Objective:
Many studies have evaluated the risk of migraine headache
in obese persons, suggesting controversial conclusions. The aim of this systematic review and meta-
analysis of the observational studies was to clarify the association between migraine and obesity.

Methods:
Scopus and PubMed electronic databases were systematically searched up to February
2019 for observational studies providing data dealing with migraine disorder in obese subjects, as
well as normal-weight controls. The random effects model was applied for assessing pool effect
size, and inter-study heterogeneity was evaluated by conducting subgroup analyses.

Results:
Among 1122 publications, 16 studies (10 cross-sectional, 5 cohort studies and 1 case-control
study) were detected and were included in the meta-analysis. The pooled data analysis illustrated
an elevated risk of migraine headache (Prevalence ratio estimate = 1.29, 95% CI, 1.15 - 1.44, p
= 0.000) in obese individuals compared to normal-weight persons. Subgroup analyses revealed that
geographical distribution was an important source of heterogeneity (p = 0.04). Significantly greater
migraine prevalence was found in European and Asian patients, but no statistically significant relationship
with obesity was observed in American patients.

Conclusions:
Based on a cumulative meta-analysis of available studies indicating an association between
migraine and obesity, obesity can be appropriately considered as an overall risk factor for migraine
headaches. Additional high-quality original studies considering frequency, severity, and duration
of headaches are required to clarify confident evidence.
Changing Demographics of NIDDK-Funded Physician-Scientists Doing Kidney Research
Authors: Abood Delaney C. , King Spencer A. , Eaton Douglas C. , Wall Susan M. 
Published: July 2021

Background and objectives
Although US physician-scientists have made enormous contributions to biomedical research, this workforce is thought to be getting smaller. However, among kidney researchers, changes have not been fully quantified.

Design, setting, participants, & measurements
We mined National Institutes of Health RePORTER to explore demographic changes of early-career and established physician and nonphysician principal investigators doing kidney-focused research. We searched for National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)–funded K series and R01 awards focused on the kidney that were active between 1990 and 2020 and determined if their emphasis was basic or clinical science. We then used public databases available on the internet to determine if these funded investigators were physicians or nonphysicians, the year in which they received either their MD (physicians) or their terminal graduate degree (nonphysicians), their sex, and whether they received their terminal degree from a US or international institution.

Results
Kidney-focused R01-funded principal investigators are aging, particularly among physicians. Moreover, the relative representation of physicians among both early-career and established principal investigators is falling, particularly among those doing basic science research. In contrast, the number and relative representation of nonphysician-scientists are increasing. There is also greater representation of women and international graduates among physician and nonphysician R01-funded, kidney-focused NIDDK investigators. However, although there are greater numbers of women physician principal investigators doing both basic as well as clinical research, women physician principal investigators are increasingly more likely to do clinical rather than basic science research.

Conclusions
The physician-scientist workforce is increasingly made up of women and international medical graduates. However, the physician-scientist workforce is older and represents a smaller proportion of all principal investigators, particularly among those doing basic science research.
MYRICETIN NANO-PHYTOSOMES PEEL-OFF GEL MASK FORMULATION AS ANTIOXIDANT
Authors: PURNAMASARI NUR AINI DEWI , DZAKWAN MUHAMMAD , PRAMUKANTORO GANET EKO , MAULUDIN RACHMAT , ELFAHMI  
Published: July 2021

Objective: Peel-off gel mask is an alternative preparation which can increase the convenience of use and is expected to increase the antioxidant activity of myricetin nano-phytosomes. Myricetin has various activities, namely as a natural antioxidant, anti-inflammatory, allergy, and anti-cancer. This study aims to determine the nano-phytosome myricetin can be formulated into a gel peel-off mask, determine the concentration of PVA which has the best physical properties of the gel peel-off mask, and determine the antioxidant activity.
Methods: The thin layer hydration method was used to manufacture Myricetin nano-phytosomes, then dried using the freeze-drying method. The resulting nano-phytosome characterization included particle size, polydispersion index, zeta potential and absorption efficiency. Peel-off gel mask were made with variations in the concentration of the PVA gelling agent, namely F1 3.5%, F2 7%, F3 14%. The resulting peel-off gel mask was tested for physical quality including organoleptic test, homogeneity, pH, viscosity, adhesion, drying time and testing for antioxidant activity.
Results: The resulting peel-off gel mask has the good physical quality and met the existing requirements, where the different PVA concentrations resulted in different physical qualities, the higher the PVA, the faster the dry time. All three formulas exhibited very strong antioxidant activity based on DPPH assay with IC50 value of 14.8 ppm (F1), 15.37 ppm (F2), and 15.87 ppm (F3).
Conclusion: Myricetin nano-phytosomes can be formulated into a gel peel-off mask, Formula 2 with a 7% concentration of PVA produces the best physical quality of the peel-off gel mask, the three gel peel-off mask formulas have excellent antioxidant activity.
OPTIMIZATION OF STARCH CROTONATE AS A NOVEL SUPERDISINTEGRANT IN THE FORMULATION OF FAST DISSOLVING TABLETS THROUGH 23 FACTORIAL DESIGN
Authors: PRAKASH RAO A. HARI OM , RADA SANTOSH KUMAR , KANDUKURI SHAMBHAVI 
Published: July 2021

Objective: To synthesize, characterize and evaluate starch crotonate as a superdisintegrant in the formulation of Piroxicam fast dissolving tablets by employing 23 factorial design.
Methods: Starch crotonate was synthesized and its physical and micromeritic properties were performed to evaluate it. The fast dissolving tablet of Piroxicam were prepared by employing starch crotonate as a superdisintegrant in different proportions in each case by direct compression method using 23 factorial design.
Results: The starch chrotonate prepared was found to be fine, free flowing and amorphous. Starch crotonate exhibited good swelling in water with swelling index (50%). The study of starch crotonate was shown by fourier transform infrared spectra (FTIR). The drug content (100±5%), hardness (3.6–4 kg/sq. cm), and friability (<0.15%) have been effective with regard to all the formulated fast dissolving tablets employing starch crotonate. The disintegration time of all the formulated tablets was found to be in the range of 18±03 to 66±03 sec. The optimized formulation F8 had the least disintegration time i.e., 18±03 sec. The wetting time of the tablets was found to be in the range of 49.92±0.11 to 140±0.18s. The In vitro wetting time was less (i.e., 74±0.37s) in optimized formulation F8. The water absorption ratio of the formulated tablets was found to be in the range of 27.58±0.01 to 123.07±0.33%. The percent drug dissolved in the optimized formulation F8 was found to be 99.83% in 10 min.
Conclusion: Starch crotonate, when combined with sodium starch glycolate, croscarmellose sodium, with Piroxicam was found to be an effective super disintegrant which improved the dissolution efficiency and could therefore be used in the formulation of quick dissolving tablets to provide immediate release of the contained drug within 10 min.
DEVELOPMENT AND IN VITRO ASSESSMENT OF BUSPIRONE LOADED IN SITU NANOEMULSION GEL
Authors: TRIPATHI KAMALESH , MANNA NIRANJAN KUMAR 
Published: July 2021

Objective: Buspirone, is a medication primarily used for generalized anxiety disorder (GAD), relieve symptoms of anxiety and unipolar depression. This drug exhibit low bioavailability (approximately 5%) due to extensive first-pass metabolism and non-targeted delivery results in numerous side effects. It is taken by mouth, and it may take up to four weeks to have an effect. The present investigation aimed at the development of buspirone in situ nanoemulsion gel to evaluate its potential for efficacious nose to brain drug delivery.
Methods: Buspirone-loaded nanoemulsions (BNEs) were prepared by aqueous titration (Spontaneous emulsification) method using Oleic acid, Tween 80, and PEG 400 as oil, surfactant and cosurfactant respectively. The NEs (FC1-FC8) were characterized for pharmaceutical characteristics (Appearance, thermodynamic stability, polydispersity index (PDI) value, globule size, pH, Viscosity, Conductivity and Refractive index). In vitro drug release study from nanoemulsions (NEs) was carried out using Keshary–Chien cell (KC cell, 25 ml) in phosphate buffer pH 5.5.
Results: Formulation FC5 with mean globule size of 105.4±1.10 nm, PDI value 0.230±0.01 and drug release 90±0.39% in 6 h (h) was developed as mucoadhesive nanoemulsion gel formulation with 17.5 % W/W of Pluronic F127. The nanoemulsion gel was homogenous, transparent, and possessed a bioadhesive strength of 1605 Dyne/cm2. In vitro cumulative drug release was found to be 90.00±0.39 % at the end of 6 h.
Conclusion: The gel had no effect on the structural integrity of nasal mucosa. Hence, the study postulates that In situ nanoemulsion gel of buspirone could be used as an intranasal formulation for targeted brain delivery via nasal route.
EFFECT OF STERILIZATION USING GAMMA RADIATION ON THE PHYSICOCHEMICAL PROPERTIES OF GEL CONTAINING ALOE VERA POWDER
Authors: BUDIMAN ARIF 
Published: July 2021

Objective: This study aims to prepare sterile gel containing aloe vera (AV) powder and evaluate its physicochemical properties after sterilization by gamma radiation.
Methods: The gel was prepared using carbomer as stabilizer, and sterilized by gamma radiation. The physical stability was evaluated including organoleptic, pH, viscosity and sterilization. Furthermore, malic acid concentration was determined as a marker compound contained in the gel.
Results: The gel was successfully prepared containing 20% AV powder and 25% carbomer. The physical properties including organoleptic, pH and viscosity were not significantly changed after sterilization, and also stable even after 28 storage days. Meanwhile, malic acid concentration before and after sterilization were 47.2 mg/ml and 43.9 mg/ml, respectively. This showed the physicochemical properties were not significantly different after sterilization.
Conclusion: Gamma radiation is suitable to sterilize gel containing AV powder.
Poeta entre pintores
Authors: Perloff Marjorie , Mattoso Ana Clara , Brandão Augusto Melo 
Published: July 2021

O ensaio trata da relação entre a obra poética de Frank O’Hara e a pintura, em especial com as vanguardas do expressionismo abstrato na cena artística da Nova York dos anos 1950 e 1960. O texto integra o terceiro capítulo do livro homônimo escrito pela crítica e ensaísta Marjorie Perloff, todavia inédito em língua portuguesa. Analisando as relações de O’Hara com artistas visuais no plano afetivo, intelectual, profissional e artístico, Perloff enfatiza as experimentações formais desse autor cuja poesia foi diretamente influenciada pela action painting, pelo happening e pela sua atuação como crítico e curador do MOMA. O ensaio apresenta ainda duas colaborações artísticas de O’Hara com os pintores Larry Rivers e Norman Bluhm, que Perloff denomina poemapinturas, dado o entrelugar formal que os caracteriza, poeta e pintor agindo simultaneamente sobre uma mesma superfície. Poesia e pintura revelam-se, na obra de O’Hara, partes de uma mesma matéria vivente. (Resumo e palavras-chave elaborados pelos tradutores).
Coronavirus infection in patients with HIV infection, features of the course
Authors: Stepanova E. V. , Leonova O. N. , Shelomov A. S. , Vinogradova T. N. 
Published: July 2021

Purpose. Analyze and identify the features of the course of the new coronavirus infection (COVID-19) in HIV-infected patients.Materials and methods. An analysis of the course of coronavirus infection (COVID-19) was carried out in 16 patients with HIV infection who were hospitalized at the St. Petersburg State Budgetary Healthcare Institution Center for the Prevention and Control of AIDS and Infectious Diseases from April to October 2020. All patients underwent a study of biological material from the oropharynx and nasopharynx for COVID-19 and diagnosed based on a positive PCR result.Results. In HIV-infected patients with diagnosed coronavirus infection caused by COVID-19, signs of progression of HIV infection, clinical, immunological, virological (75%), opportunistic diseases and comorbidities (chronic viral hepatitis in the cirrhotic decompensated stage, cardiovascular diseases and others) (94%). A small sample of patients did not allow to determine with reliable accuracy the mutual influence of existing diseases and pathologies, but, of course, multiple comorbid pathologies play a role in the development of severe conditions and unfavorable outcomes. A clinical case is presented.Conclusion. The provoking factors have been identified that play a role in the development of infection and more severe forms of coronavirus infection caused by COVID-19 in HIV-infected patients (injecting drug use, alcohol abuse, late stage of HIV infection (4B, 4C) and progression of earlier stages (4A ), a low number of CD4 lymphocytes (less than 200 cells / μl), multiple comorbid pathology (HIV infection, opportunistic diseases, comorbidities, especially chronic liver damage in the stage of decompensated cirrhosis), absence, interrupted antiretroviral therapy, multiple changes of regimens, absence prevention of opportunistic diseases). A patient with HIV infection at ART. 4B with multiple comorbidity, the possibility of long-term persistence of the COVID-19 virus coronavirus with positive and negative results for more than 2 months and later development of lung damage caused by COVID-19 was established.
Relationship between expression of HBV-infection markers in placenta and clinical data of mothers and their newborns
Authors: Belopolskaya M. A. , Karev V. E. , Avrutin V. Yu. , Dmitriev A. V. , Gusev D. A. 
Published: July 2021

Vertical transmission of viral hepatitis B (HBV) is one of the main transmission ways in endemic regions. There is a relationship between structural changes in the placenta and the clinical course of HBV infection. The risk of vertical transmission of hepatitis B depends on the condition of the placenta.The goal of this work was to study the relationship between HBsAg and / or HBcorAg expression in placenta on the one hand, and clinical parameters of mothers and newborns on the other hand.The study included 19 patients with CHB who gave birth at the Botkins infectious disease hospital in 2019. The first group included patients with markers of HBV infection (HBsAg and / or HBcorAg) detectable via immunohistochemical examination in at least one of the layers of the placenta. In patients from the second group, no markers of HBV infection were detected in any layer of the placenta. Inflammatory changes in placenta were detected in all women from the first group and in 9 (64%) women from the second group. HBsAg in umbilical cord blood was detected in 3 (16%) newborns. In two patients, whose children had HBsAg in the umbilical cord blood, no markers of HBV infection were detected in placenta. In the first group, only one newborn had HBsAg in umbilical cord blood. In two patients receiving an antiviral treatment during pregnancy, markers of HBV infection were identified in the placenta. Markers of HBV infection in placenta were also detected in women with undetectable viral load.ConclusionsMarkers of HBV infection can be found in placenta at low maternal viral load.HBsAg in umbilical cord blood can be detected even in patients with no markers of HBV infection in placenta.Antiviral treatment during pregnancy does not prevent the possibility of placenta’s infection with HBV.
The research on COVID-19 and economy from 2019 to 2020: analysis from the perspective of bibliometrics
Authors: Liu Nana , Xu Zeshui , Skare Marinko 
Published: July 2021

Research background: The outbreak and spread of COVID-19 brought disastrous influences to the development of human society, especially the development of economy.
Purpose of the article: Considering that knowing about the situations of the existing studies about COVID-19 and economy is not only helpful to understand the research progress and the connections between COVID-19 and economy, but also provides effective suggestions for fighting against COVID-19 and protecting economy, this paper analyzes the existing studies on COVID-19 and economy from the perspective of bibliometrics.
Methods: Firstly, the discussion starts from the statistical analysis, in which the basic distributions of the studies on different countries/regions, different publication sources, different publication years, etc., are presented. Then, the paper shows the cooperation situations of the researchers from analyzing the related citation networks, co-citation networks and cooperation networks. Further, the theme analysis of the related studies is presented, in which the related co-occurrence networks are shown, and then the detailed analyses of the studies are introduced. Based on these analyses, the discussions about future research are presented, and finally we draw a conclusion.
Findings & value added: The analyses not only present the basic situation on the research about COVID-19 and Economy, but also show the future research trends, which can provide meaningful research expectations.