Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein–Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis

Introduction: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world’s population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India. Methodology: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)– EBV PCR and Epstein–Barr virus latent membrane protein 1 (LMP1) IHC. Results: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection. Conclusion: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.
Quality of Life of Family Caregivers of Cancer Patients in a Developing Nation

Background: Quality of life (QOL) of family caregivers of cancer patients is usually affected due to increase in caregiver burden. Their QOL has not garnered much attention by many including the health professionals and community. This study aims to explore the QOL of family caregivers of cancer patients in a multi-ethnic country in Asia and to investigate its associate factors. Methods: This is a cross-sectional study where family caregivers and patients who were diagnosed of cancers within 12 months were recruited. QOL of caregivers were measured using The Caregiver Quality of Life Index-Cancer (CQOLC). Psychological distress was measured using Hospital anxiety and depressive scale. Logistic regression analysis was performed to determine the related factors of QOL of caregivers. Results: A total of 458 patients/caregiver pairs were included. Symptoms of anxiety and depression reported by caregivers were 24.9% and 24.2% respectively. Caregivers of patients with solid tumors have better CQOLC score compared to those who cared for patients with hematological cancers (91.25 vs 86.75). Caregivers of non-Malay ethnicity, those caring for patients with advanced stage cancer and with hematological cancers had significantly poorer QOL. QOL of caregivers are also significantly affected when patients demonstrated anxiety symptoms. Conclusion: This study provides detailed evaluation of the QOL of caregivers of cancer patients in Malaysia. The significant psychological distress and low caregiver QOL indicate the urgent need for comprehensive supports for caregivers with cancer patients, especially those caring for patients with haematological cancers.
The Spectrum of Infections in Patients with Lung Cancer

Abstract Although diagnostic and therapeutic advances in lung cancer (LC) have increased the survival of patients, infection and its complications are still among the most important causes of mortality. The disruption of tissue caused by tumor mass, management of cancer therapy and alteration in the humoral/cellular immune systems due to both cancer itself and therapy considerably increase susceptibility to infection in cancer patients. Particularly, opportunistic microorganisms should be considered, then applying rapid and sensitive diagnostic methods for them. Thus, cancer patients who are already exposed to difficult, long-term and expensive treatments can be prevented from dying from complications related to infections.
Interfacial characteristics of BIOfactor MTA and Biodentine with dentin

The objective of this study was to characterize the interface between dentin and MTA‐Angelus (Angelus, Londrina, Brasil), Biodentine (Septodont, France) and BIOfactor MTA (Imicryl, Konya, Turkey) using scanning electron microscopy (SEM), energy disperse X‐ray spectroscopy (SEM‐EDS) and confocal laser scanning microscopy (CLSM). Fifteen dentin segments were obtained from previously extracted single‐rooted human teeth. Canal lumens were instrumented with diamond burs and then randomly filled with MTA‐Angelus, Biodentine or BIOfactor MTA and placed in distilled water or Hanks' Balanced Salt Solution (HBSS) for 28‐days. The samples were examined with SEM and the thickness of the interfacial layer measured. SEM‐EDS analysis was performed to determine principal elemental composition of the material, dentin, and interfacial area. The marginal adaptation of cements to dentin was assessed by confocal microscopy and the percentage of material penetration was calculated. An interfacial layer was evident in approximately 70% of SEM images in both MTA‐Angelus and BIOfactor samples. The thickness of interfacial layer was significantly higher in HBSS than in distilled water for all groups. MTA Angelus resulted in the thickest interfacial layer in distilled water while Biodentine had the thickest interfacial layer in HBSS. Calcium levels within the BIOfactor MTA–dentin interface were higher than both dentin and cement. Dentin penetration was higher in BIOfactor MTA and silicon was evident in all material‐dentin interfaces. All calcium silicate‐based materials promoted the formation of an interfacial layer. BIOfactor MTA exhibited promising characteristics with its good marginal adaptation even though it presented a moderately thick interfacial layer.
Feasibility and tolerability of sintilimab plus anlotinib as the second‐line therapy for patients with advanced biliary tract cancers: An open‐label, single‐arm, phase II clinical trial

Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first‐line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second‐line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first‐line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1‐14.5). Only four (20%) patients were observed of the grade 3 treatment‐related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti‐tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently.
A study of the threshold method utilizing raingage data

Abstract The threshold method for estimation of area-average rain rate relies on determination of the fractional area where rain rate exceeds a preset level of intensity. Previous studies have shown that the optimal threshold level depends on the climatological rain-rate distribution (RRD). It has also been noted, however, that the climatological RRD may be composed of an aggregate of distributions, one for each of several distinctly different synoptic conditions, each having its own optimal threshold. In this study, the impact of RRD variations on the threshold method is shown in an analysis of 1-min rain-rate data from a network of tipping-bucket gauges in Darwin, Australia. Data are analyzed for two distinct regimes: the premonsoon environment, having isolated intense thunderstorms, and the active monsoon rains, having organized convective cell clusters that generate large areas of stratiform rain. It is found that a threshold of 10 mm h−1 results in the same threshold coefficient for both regimes, sug.
On the nature of the dark mass in the centre of the Milky Way

We discuss constraints on the properties and nature of the dark mass concentration at the core of the Milky Way. We present 0.15-arcsec astrometric K-band maps in five epochs beween 1992 and 1996. From these we derive imposed stellar proper motions within 3 arcsec of the compact radio source Sgr A * whose infrared counterpart may have been detected, for the first time, in a deep image in 1996 June. We also report AI AA '" 35 speckle spectroscopy and show that several of the Sgr A * (infrared) cluster members are likely early-type stars of mass '" 15 to 20 M 0 . All available checks, including a first comparison with high-resolution maps that are now becoming available from other groups, support our previous conclusion that there are several fast-moving stars (2::: 10 3 km S-I) in the immediate vicinity (0.01 pc) of Sgr A * . From the stellar radial and proper motion data, we infer that a dark mass of 2.61 (± 0.15 stat)( ± 0.35 stat+sys) X 10 6 M0 must reside within about one light-week of the compact radio source. Its density must be 2.2 x 10 12 M0 pc- 3 or greater. There is no stable configuration of normal stars, stellar remnants or sub stellar entities at that density. From an equipartition argument we infer that at least 5 per cent of the dark mass ( 2::: 10 5 M 0 ) is associated with the compact radio source Sgr A * itself and is concentrated on a scale of less than 15 times the Schwarzschild radius of a 2.6 x 106-M0 black hole. The corresponding density is 3 x 10 20 M0 pc- 3 or greater. If one accepts these arguments it is hard to escape the conclusion that there must be a massive black hole at the core of the Milky Way.
Effect of an mHealth intervention on physical activity outcomes among young adult cancer survivors: The IMPACT randomized controlled trial

Physical inactivity is common in young adult cancer survivors (YACS), but evidence regarding effects of physical activity (PA) interventions among YACS is limited. The IMproving Physical Activity after Cancer Treatment (IMPACT) trial evaluated a theory‐based mobile PA intervention on total PA minutes/week (primary) and secondary outcomes (moderate‐to‐vigorous PA [MVPA], light PA, steps, sedentary behaviors) at 6 months in YACS.
Diabetes, metformin use and risk of non‐Hodgkin's lymphoma in postmenopausal women: A prospective cohort analysis in the Women's Health Initiative

Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non‐Hodgkin's lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women's Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow‐up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B‐cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable‐adjusted Cox proportional hazards models. During a median follow‐up of 18.86 years (range, 0.01‐25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self‐reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable‐adjusted model HR = 1.38, 95% CI (1.06‐1.81) and HR = 1.55, 95% CI (1.16‐2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable‐adjusted model: HR = 1.28, 95% CI (1.06‐1.54) and HR = 1.56, 95% CI (1.13‐2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13‐2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well‐designed research is needed to confirm our findings.
Statistical studies of flux transfer events

Previous studies have revealed that flux transfer events (FTEs) have a clear dependence on the interplanetary magnetic field Bz component. Herein we examine other solar wind parameters, beta, dynamic pressure, and Mach number that possibly control the formation of FTEs. None of these other parameters appear to exercise strong control of the rate of FTE occurrence. Hence we conclude that the occurrence of FTEs is probably controlled by some intrinsic property of the magnetospheric system itself rather than by these solar wind parameters. In order to examine whether the bipolar signatures observed in the magnetosheath or magnetosphere are the same phenomenon, magnetosheath FTEs and magnetospheric FTEs are studied separately. The similar results for the two types of FTEs indicate that they do belong to the same statistical population.
Molecular dynamics simulation study on Bacillus subtilis EngA: the presence of Mg2+ at the active-sites promotes the functionally important conformation

Abstract EngA, a GTPase contains two GTP binding domains [GD1, GD2], and the C-terminal KH domain shown to be involved in the later stages of ribosome maturation. Association of EngA to the ribosomal subunit in the intermediate stage of maturation is essential for complete ribosome maturation. However, this association was shown to be dependent on the nucleotide bound combinations. This nucleotide dependent association tendency is attributed to the conformational changes that occur among different nucleotide bound combinations. Therefore, to explore the conformational changes, all-atom molecular dynamics simulations for Bacillus subtilis EngA in different nucleotide bound combinations along with the presence or absence of Mg2+ in the active-sites were carried out. The presence of Mg2+ along with the bound nucleotide at the GD2 active-site dictates the GD2-Sw-II mobility, but the GD1-Sw-II mobility has not shown any nucleotide or Mg2+ dependent movement. However, the GD1-Sw-II secondary conformations are shown to be influenced by the GD2 nucleotide bound state. This allosteric connection between the GD2 active-site and the GD1-Sw-II is also observed through the dynamic network analysis. Further, the exploration of the GD1-KH interface interactions exhibited a more attractive tendency when GD1 is bound to GTP-Mg2+. In addition, the presence of Mg2+ stabilizes active-site water and also increases the distances between the α- and γ- phosphates of the bound GTP. Curiously, three water molecules in the GD1 active-site and only one water molecule in the GD2 active-site are stabilized. This indicates that the probability of GTP hydrolysis is more in GD1 compared to GD2. Communicated by Ramaswamy H. Sarma
The multifaceted role of GCM1 during trophoblast differentiation in the human placenta

Significance Proper placental development is critical for pregnancy success. Placental maldevelopment is linked with serious pregnancy complications that jeopardize the health of both mother and child. The parenchymal cells of the placenta are trophoblasts, which arise from trophoblast stem cells differentiating through one of two distinct lineage pathways: syncytiotrophoblast, which regulates maternal-fetal nutrient transfer, and extravillous trophoblasts (EVTs), which remodel the uterine vasculature. Glial cells missing-1 (GCM1) is a transcription factor classically associated with syncytiotrophoblast formation, but GCM1 is also expressed in EVTs. In this study, human trophoblast stem cells were used to corroborate the role of GCM1 in syncytiotrophoblast formation and uncover its critical role in EVT development. We conclude that GCM1 contributes to multiple aspects of human placentation.
Longitudinal health behaviour patterns among adults aged ≥50 years in China and their associations with trajectories of depressive symptoms

Abstract Objectives Against the background of the growing recognition of the need for a holistic perspective on health behaviour, we aim to identify longitudinal patterns of multiple health behaviours, and to assess associations of such patterns with depressive symptoms among older people in China. Methods Using three waves of China Health and Retirement Longitudinal Study data (n = 8439), we performed latent class growth analyses (LCGAs) to identify longitudinal patterns of multiple health behaviours. Random-effects models were estimated to assess associations between health behaviour patterns and depressive symptoms. Results The best fitting LCGA model had seven classes: (1) connected active non-smokers (average posterior probability: 21.8%), (2) isolated active non-smokers (24.7%), (3) isolated inactive non-smokers (17.0%), (4) isolated active smokers (14.5%), (5) connected active smokers (12.2%), (6) increasingly connected and active non-smokers (5.4%), and (7) moderately connected inactive smokers (4.4%). Depressive symptoms were highest in the four classes with lower probabilities of social participation across waves. No evidence was found of change over time in depressive symptomatology gaps between people with different health behaviour trajectories. Conclusion Health behaviour patterns characterized by consistently low social participation were associated with raised depressive symptomatology, suggesting that focusing on social participation may benefit later-life mental health promotion strategies.
Joint Analysis of Phenotypic and Genomic Diversity Sheds Light on the Evolution of Xenobiotic Metabolism in Humans

Abstract Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to a therapeutic treatment. The study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is, however, scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein (P-gp) activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East, and Europe (349 healthy Ethiopian, Omani, Greek, and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. Genome-wide association studies (GWAS) evidenced that the variability of phenotypes measuring CYP2B6, CYP2C9, CYP2C19, and CYP2D6 activity was associated with genetic variants linked to the corresponding encoding genes, and additional genes for the latter three. Instead, GWAS did not indicate any association between genetic diversity and the phenotypes measuring CYP1A2, CYP3A4, and P-gp activity. Genome scans of selection highlighted multiple candidate regions, a few of which included ADME genes, but none overlapped with the GWAS candidates. Our results suggest that different mechanisms have been shaping the evolution of these phenotypes, including phenotypic plasticity, and possibly some form of balancing selection. We discuss how these contrasting results highlight the diverse evolutionary trajectories of ADME genes and proteins, consistent with the wide spectrum of both endogenous and exogenous molecules that are their substrates.
Clerodane diterpene induces apoptosis/anoikis and suppresses migration and invasion of human bladder cancer cells through the histone deacetylases, integrin–focal adhesion kinase, and matrix metalloproteinase 9 signalling pathways

Clerodane diterpene, a class of bicyclic diterpenoids, is found in hundreds of plant species. 16-hydroxycleroda-3,13-dien-15,16-olide (CD) can be isolated from the plant Polyalthia longifolia and has been applied against oral cancer and glioma by xenograft model. In this study, we aim to explore its antitumour action by examining its histone deacetylase (HDAC) activity and integrin-associated intracellular signalling pathway on T24 human bladder cancer (BC) cells. Our results revealed that CD-inhibited colony formation, HDAC activity, HDAC (1, 2 and 3) mRNA and cell spreading on fibronectin-coated surfaces in a concentration-dependent manner. Furthermore, decreased cFLIP and increased caspase-8 cleavage accompanied CD-induced cell death. At non-toxic concentrations, CD blocked the migration and invasion of T24 cells. CD hindered migration and invasion by the downregulation of fibronectin, integrin α5β1, β-catenin, FAK, vinculin and Rho A, as well as by reduction of phosphorylated glycogen synthase kinase 3β (pGSK3β), pSrc, pstat3 and pNFκB. We observed that the MMP9 gene was closely linked with prognosis of patients with bladder cancer. MMP9 protein levels and activity were largely attenuated by CD in a concentration-dependent manner. In conclusion, CD-induced caspase-8-dependent apoptosis and suppressed migration and invasion by blocking several intracellular signalling pathways, including downregulation of HDAC activity and integrin–FAK and MMP9 pathways.
E-Cigarette Use among University Students from One University in Hanoi, Vietnam, and Associated Factors

Objective: Describe the use of e-cigarettes and factors associated with e-cigarette use among university students from one university in Vietnam in 2021. Methods: This cross-sectional study was conducted with a total of 554 full-time undergraduate students recruiting for the study. Data was collected using a structured self-administered questionnaire. A logistic regression analysis was performed to identify factors with significant association with students’ use of e-cigarettes. Results: The study revealed that 13.2% of students were current users. Students who had e-cigarette smokers in the family (aOR=6.1, 95% CI: 2.5-15.4; p<0.001), used traditional cigarettes (aOR=23.6, 95% CI: 10.5-53.4; p<0.001), consumed alcohol (aOR=5, 95%CI: 1.6 – 15.9; p<0.01), were exposed to e-cigarette advertising (aOR=2.6; 95%CI: 1.1-5.9; p<0.01), and had inadequate knowledge about e-cigarettes (aOR=2.2; 95%CI: 1-4.7; p<0.01) were more likely to use e-cigarettes. Conclusion: This study updates the status of e-cigarette use among students in one university in Vietnam, thereby suggesting strategies to reduce the use of e-cigarettes among university students.
Magnetic-field asymmetry of nonlinear transport in a small ring

We have investigated the magnetic-field asymmetry of the conductance in the nonlinear regime in a small Aharonov-Bohm ring. We have found that the odd-in B and linear in V (the DC bias) correlation function of the differential conductance exhibits periodical oscillations with the Aharonov-Bohm flux. We have deduced the electron interaction constant and analyzed the phase rigidity of the Aharonov-Bohm oscillations in the nonlinear regime.