Miracle-dz/UniFAR-FTUs huggingface dataset:
Robustly leveraging the post-randomization information to improve precision in the analyses of randomized clinical trials

In randomized clinical trials, repeated measures of the outcome are routinely collected. The mixed model for repeated measures (MMRM) leverages the information from these repeated outcome measures, and is often used for the primary analysis to estimate the average treatment effect at the final visit. MMRM, however, can suffer from precision loss when it models the intermediate outcomes incorrectly, and hence fails to use the post-randomization information in a harmless way. In this paper, we propose a new working model, called IMMRM, that generalizes MMRM and optimizes the precision gain from covariate adjustment, stratified randomization and adjustment for intermediate outcome measures. We prove that the IMMRM estimator for the average treatment effect is consistent and asymptotically normal under arbitrary misspecification of its working model assuming missing completely at random. Under simple or stratified randomization, the IMMRM estimator is asymptotically equally or more precise than the analysis of covariance (ANCOVA) estimator and the MMRM estimator. By re-analyzing three randomized trials in the diabetes therapeutic area, we demonstrate that the IMMRM estimator has 2-24% smaller variance than ANCOVA and 5-16% smaller variance than MMRM.
Fair and Efficient Allocations of Chores under Bivalued Preferences

We study the problem of fair and efficient allocation of a set of indivisible chores to agents with additive cost functions. We consider the popular fairness notion of envy-freeness up to one good (EF1) with the efficiency notion of Pareto-optimality (PO). While it is known that EF1+PO allocations exists and can be computed in pseudo-polynomial time in the case of goods, the same problem is open for chores. Our first result is a strongly polynomial-time algorithm for computing an EF1+PO allocation for bivalued instances, where agents have (at most) two disutility values for the chores. To the best of our knowledge, this is the first non-trivial class of chores to admit an EF1+PO allocation and an efficient algorithm for its computation. We also study the problem of computing an envy-free (EF) and PO allocation for the case of divisible chores. While the existence of EF+PO allocation is known via competitive equilibrium with equal incomes, its efficient computation is open. Our second result shows that for bivalued instances, an EF+PO allocation can be computed in strongly polynomial-time.
Identification of tissue optical properties during thermal laser‐tissue interactions: An ensemble Kalman filter‐based approach

In this article, we propose a computational framework to estimate the physical properties that govern the thermal response of laser‐irradiated tissue. We focus in particular on two quantities, the absorption and scattering coefficients, which describe the optical absorption of light in the tissue and whose knowledge is vital to correctly plan medical laser treatments. To perform the estimation, we utilize an implementation of the ensemble Kalman filter (EnKF), a type of Bayesian filtering algorithm for data assimilation. Unlike prior approaches, in this work, we estimate the tissue optical properties based on observations of the tissue thermal response to laser irradiation. This method has the potential for straightforward implementation in a clinical setup, as it would only require a simple thermal sensor, for example, a miniaturized infrared camera. Because the optical properties of tissue can undergo shifts during laser exposure, we employ a variant of EnKF capable of tracking time‐varying parameters. Through simulated experimental studies, we demonstrate the ability of the proposed technique to identify the tissue optical properties and track their dynamic changes during laser exposure, while simultaneously tracking changes in the tissue temperature at locations beneath the surface. We further demonstrate the framework's capability in estimating additional unknown tissue properties (i.e., the volumetric heat capacity and thermal conductivity) along with the optical properties of interest.
Characterization of the Function of Two S1Fa-Like Family Genes From Populus trichocarpa

S1Fa-like transcription factors (TFs) are small molecular weight proteins that contain both nuclear localization and DNA binding domains. However, the functions of S1Fa-like TFs are poorly understood. In the present study, we identified the S1Fa-like TFs from the Populus trichocarpa genome, which revealed two S1Fa-like TF genes, PtS1Fa1 and PtS1Fa2. PtS1Fa1 and PtS1Fa2 expression was suppressed by drought and salt stress, and was also significantly altered by ABA, MeJA, or SA treatment. Both PtS1Fa1 and PtS1Fa2 are nuclear proteins. Transgenic P. trichocarpa plants overexpressing PtS1Fa1 and PtS1Fa2, respectively, were generated. The plants overexpressing PtS1Fa2 showed increased fresh weight, chlorophyll content, and root length and weight compared with those in wild-type (WT) P. trichocarpa under drought conditions. Meanwhile, these phenotype traits of plants overexpressing PtS1Fa1 were similar to those of WT plants. Furthermore, overexpression of PtS1Fa2 reduced the malondialdehyde (MDA) content, electrolyte leakage, H2O2 and O2- contents, and increased superoxide dismutase (SOD) and peroxidase (POD) activities. The expression of SOD and POD was also induced by PtS1Fa2. However, overexpression of PtS1Fa1 failed to affect any of these physiological parameters or SOD and POD gene expression. These results suggested that PtS1Fa2 plays a role in drought tolerance, and confers drought tolerance by increase antioxidant activity to reduce reactive oxygen species (ROS) accumulation.
Identification of Significant Genes in Lung Cancer of Nonsmoking Women via Bioinformatics Analysis

Background The aim of this study was to identify potential key genes, proteins, and associated interaction networks for the development of lung cancer in nonsmoking women through a bioinformatics approach. Methods We used the GSE19804 dataset, which includes 60 lung cancer and corresponding paracancerous tissue samples from nonsmoking women, to perform the work. The GSE19804 microarray was downloaded from the GEO database and differentially expressed genes were identified using the limma package analysis in R software, with the screening criteria of p value < 0.01 and ∣log2 fold change (FC) | >2. Results A total of 169 DEGs including 130 upregulated genes and 39 downregulated were selected. Gene Ontology and KEGG pathway analysis were performed using the DAVID website, and protein-protein interaction (PPI) networks were constructed and the hub gene module was screened through STING and Cytoscape. Conclusions We obtained five key genes such as GREM1, MMP11, SPP1, FOSB, and IL33 which were strongly associated with lung cancer in nonsmoking women, which improved understanding and could serve as new therapeutic targets, but their functionality needs further experimental verification.
Recent Advances in Three-Dimensional Stem Cell Culture Systems and Applications

Cell culture is one of the most core and fundamental techniques employed in the fields of biology and medicine. At present, although the two-dimensional cell culture method is commonly used in vitro, it is quite different from the cell growth microenvironment in vivo. In recent years, the limitations of two-dimensional culture and the advantages of three-dimensional culture have increasingly attracted more and more attentions. Compared to two-dimensional culture, three-dimensional culture system is better to realistically simulate the local microenvironment of cells, promote the exchange of information among cells and the extracellular matrix (ECM), and retain the original biological characteristics of stem cells. In this review, we first present three-dimensional cell culture methods from two aspects: a scaffold-free culture system and a scaffold-based culture system. The culture method and cell characterizations will be summarized. Then the application of three-dimensional cell culture system is further explored, such as in the fields of drug screening, organoids and assembloids. Finally, the directions for future research of three-dimensional cell culture are stated briefly.
A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue

Abstract Background: Post-stroke fatigue seriously affects the quality of life for stroke patients. There is no effective treatment at present. transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation which may have therapeutic effect on post-stroke fatigue. This study will explore about this. Method: A total of 60 patients with post-stroke fatigue were randomly divided into the control group and the treatment group with 30 patients each by minimization randomization. Both groups received basic treatment and conventional rehabilitation. In the treatment group, patients were treated with active tDCS, while in the control group, sham tDCS. Both active and sham tDCS were administered 6 times a week for 4 weeks. Before and after the trial, the Fatigue Severity Scale (FSS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) were evaluated and analyzed. And comparisons were made among groups. And there were an 8-week follow-up after the intervention. Result: Before the intervention, there were no significant differences in baseline data and assessment scores between the groups (P > 0.05). After 4 weeks of intervention, FSS scores in the treatment group were significantly lower than those in the control group (P = 0.012), and FMA and BMI scores were significantly higher than those in the control group (P < 0.05). There was no significant change in FSS scores after 8 months of follow-up (P > 0.05). Discussion: TDCS is a safe treatment that can effectively reduce the degree of fatigue after stroke, improve the motor function and daily activity ability of patients after stroke, and the efficacy is better than only routine rehabilitation training. Trial registration number: Chinese Clinical Trial Registry, ChiCTR2000031120. Registered on March 22, 2020.
The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation

To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.
Adenoviral vector‐based platforms for developing effective vaccines to combat respiratory viral infections

Since the development of the first vaccine against smallpox over two centuries ago, vaccination strategies have been at the forefront of significantly impacting the incidences of infectious diseases globally. However, the increase in the human population, deforestation and climate change, and the rise in worldwide travel have favored the emergence of new viruses with the potential to cause pandemics. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is a cruel reminder of the impact of novel pathogens and the suboptimal capabilities of conventional vaccines. Therefore, there is an urgent need to develop new vaccine strategies that allow the production of billions of doses in a short duration and are broadly protective against emerging and re‐emerging infectious diseases. Extensive knowledge of the molecular biology and immunology of adenoviruses (Ad) has favored Ad vectors as platforms for vaccine design. The Ad‐based vaccine platform represents an attractive strategy as it induces robust humoral and cell‐mediated immune responses and can meet the global demand in a pandemic situation. This review describes the status of Ad vector‐based vaccines in preclinical and clinical studies for current and emerging respiratory viruses, particularly coronaviruses, influenza viruses and respiratory syncytial viruses.
The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL

Objective To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. Materials and Methods In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. Results PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). Conclusions For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.
Prevalence of stress, stressors, and coping strategies among medical undergraduate students in a medical college of Mumbai

BACKGROUND: Stress is a subjective experience which creates an obstacle in a person's path of achieving his or her goals. It creates negative outcomes among the population. Medical curriculum is very vast and stressful. As doctors are the very important part of society, medical students must be allowed to learn their trade in a stress-free environment. The present study aimed to assess the perceived stress, various sources of stress among medical undergraduate students, and the coping strategies adopted. MATERIALS AND METHODS: This was a cross-sectional study conducted among medical under-graduate students studying at a tertiary care hospital situated in Mumbai city of Maharashtra between January and June 2018. Using purposive sampling technique, a total of 450 medical students from 1st year to final year were invited to participate in the study. A self-administered questionnaire consisting of sociodemographic details and perceived stress scale questions was used. Logistic regression analysis was carried out to assess the determinants of stress. Odds ratio, 95% confidence interval was calculated. P < 0.05 was considered statistically significant. RESULTS: The overall response rate was 79.11%, with 356 out of 450 students returning the questionnaire. Among 356 participants, 324 participants (91%) were suffering from high levels of stress. Factors such as curriculum vastness, frequency of examination, competition with peer, performance in examinations, worry about future, loneliness, relation with opposite sex, and quality of food played a major role in creating additional stress. CONCLUSIONS: The perceived stress was higher among female medical students. Academic factors are greater perceived cause of stress in medical students in this study. A substantial proportion of medical undergraduate students were found to be stressed which necessitates appropriate and timely interventions. Reframing the academic curriculum along with examination and evaluation patterns, incorporating extracurricular activities, and establishment of counselling cells in the institution is the need of the hour.
Point-of-Care Testing for Multiple Cardiac Markers Based on a Snail-Shaped Microfluidic Chip

Existing methods for detecting cardiac markers are difficult to be applied in point-of-care testing (POCT) due to complex operation, long time consumption, and low sensitivity. Here, we report a snail-shaped microfluidic chip (SMC) for the multiplex detection of cTnI, CK-MB, and Myo with high sensitivity and a short detection time. The SMC consists of a sandwich structure: a channel layer with a mixer and reaction zone, a reaction layer coated with capture antibodies, and a base layer. The opening or closing of the microchannels is realized by controlling the downward movement of the press-type mechanical valve. The chemiluminescence method was used as a signal readout, and the experimental conditions were optimized. SMC could detect cTnI, CK-MB, and Myo at concentrations as low as 1.02, 1.37, and 4.15. The SMC will be a promising platform for a simultaneous determination of multianalytes and shows a potential application in POCT.
Development of Coriandrum sativum Oil Nanoemulgel and Evaluation of Its Antimicrobial and Anticancer Activity

This study is aimed at developing coriander oil into a nanoemulgel and evaluating its antimicrobial and anticancer effects. Coriander (Coriandrum sativum) oil was developed into a nanoemulgel by using a self-nanoemulsifying technique with Tween 80 and Span 80. Hydrogel material (Carbopol 940) was then incorporated into the nanoemulsion and mixed well. After this, we evaluated the particle size, polydispersity index (PDI), rheology, antimicrobial effect, and cytotoxic activity. The nanoemulsion had a PDI of 0.188 and a particle size of 165.72 nm. Interesting results were obtained with the nanoemulgel against different types of bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 2.3 μg/ml, 3.75 μg/ml, and 6.5 μg/ml, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the nanoemulgel when applying it to human breast cancer cells (MCF-7), hepatocellular carcinoma cells (Hep3B), and human cervical epithelioid carcinoma cells (HeLa) was 28.84 μg/ml, 28.18 μg/ml, and 24.54 μg/ml, respectively, which proves that the nanoemulgel has anticancer effects. The development of C. sativum oil into a nanoemulgel by using a self-nanoemulsifying technique showed a bioactive property better than that in crude oil. Therefore, simple nanotechnology techniques are a promising step in the preparation of pharmaceutical dosage forms.
Comparison of the effect of traditional Chinese medicine injection combined with chemotherapy and chemotherapy alone on the prognosis, quality of life and immune function in patients with ovarian carcinoma

Abstract Background: The effectiveness of traditional Chinese medicine (TCM) in assisting the reduction of the toxic effects of chemotherapy and enhancing the efficacy of chemotherapy is gradually being recognized. Traditional Chinese medicine injection (TCMJ) has been widely used as a promising adjuvant drug in the treatment of ovarian carcinoma. However, the exact clinical efficacy and safety of TCMJ have not been well studied due to the wide variety. This study aims to conduct a network meta-analysis of randomized controlled trials (RCTs) about comparing the effect of TCMJ combined with chemotherapy and chemotherapy alone on the treatment of ovarian cancer, thus summarizing the effects of TCMJ on the prognosis, quality of life and immune function of ovarian carcinoma patients, and providing a reference for developing therapeutic regimens for ovarian carcinoma. Methods: Randomized controlled trials reporting the effect of TCMJ combined with chemotherapy and chemotherapy alone on the prognosis, quality of life and immune function in patients with ovarian carcinoma published before September 2021 will be screened out from online databases like PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database. Subsequently, 2 researchers will be independently responsible for literature screening, data extraction and assessment of their quality. All data will be processed by R.4. 1.0. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusions: Evidence-based medicine supports the efficacy and safety of TCMJ combined with chemotherapy for the treatment of ovarian carcinoma, which is better than that of chemotherapy alone. Ethics and dissemination: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/P93VJ.