Miracle-dz/UniFAR-FTUs huggingface dataset:
A network pharmacological approach to reveal the multidrug resistance reversal and associated mechanisms of acetogenins against colorectal cancer

Abstract Multidrug Resistance (MDR) in tumors is caused by the over-expression of ATP Binding Cassette transporter proteins such as Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein 1. This in silico study focuses on identifying a MDR inhibitor among acetogenins (AGEs) of Annona muricata and also aims at predicting colorectal cancer (CRC) core targets of AGEs through a network pharmacological approach. Twenty-four AGEs were initially screened for their ADME properties. Molecular interaction studies were performed with the two proteins MRP1 and BCRP1. As the structure of MRP1 was not available, an inward-facing conformation of MRP1 was modeled. A Protein-protein interaction network was constructed for the correlating targets of CRC. KEGG pathway and Gene Ontology analysis were performed for the predicted CRC targets. We identified four lead AGEs: Muricatocin B, Annonacinone, Annonacin A and Annomuricin E having a higher binding affinity towards MDR proteins. MD simulation studies performed with the three lead AGEs and the MDR proteins showed that MRP1(DBD): Annomuricin E complex was stable throughout the simulation. Our analysis revealed ABCG2, ERBB2, STAT3, AR, SRC and ABCC1 as CRC targets of the lead molecules. The top 10 signaling pathways and functions of correlative CRC targets were also predicted. We conclude that the identified lead molecules might act as competitive inhibitors for reversing MDR in CRC. Additionally, network pharmacological studies established the correlative CRC targets and their mechanisms of action. Further experimental studies are needed to validate our findings. Communicated by Ramaswamy H. Sarma
A single-center analysis of patients with extranodal marginal zone lymphoma of the breast

Abstract Breast extranodal marginal zone lymphoma (EMZL) is a rare malignancy. We performed the largest published to date single-center retrospective analysis of 13 patients with breast EMZL focusing on clinical characteristics and treatment-related outcomes. The rarity of this disease at our center was concordant with the prevalence reported in the literature, with breast EMZL comprising 2% of 654 MZL cases. Most patients presented with stage I-II disease however four (30.8%) patients had stage IV disease mostly due to occult bone marrow (BM) involvement. Interestingly, EMZL was frequently non-FDG avid (66.7%) on staging PET/CT. With a median follow-up of 3.1 years (range 5 months to 10.2 years), the 3-year progression free survival was 68.7% (95%CI 30.2%–88.9%) and overall survival 80.2% (95%CI 40.3%-94.8%). No patient experienced higher-grade transformation. Herein we show that localized breast EMZL can be effectively treated with radiation therapy providing long term disease control.
Continuous Online Adaptation of Bioinspired Adaptive Neuroendocrine Control for Autonomous Walking Robots

Walking animals can continuously adapt their locomotion to deal with unpredictable changing environments. They can also take proactive steps to avoid colliding with an obstacle. In this study, we aim to realize such features for autonomous walking robots so that they can efficiently traverse complex terrains. To achieve this, we propose novel bioinspired adaptive neuroendocrine control. In contrast to conventional locomotion control methods, this approach does not require robot and environmental models, exteroceptive feedback, or multiple learning trials. It integrates three main modular neural mechanisms, relying only on proprioceptive feedback and short-term memory, namely: 1) neural central pattern generator (CPG)-based control; 2) an artificial hormone network (AHN); and 3) unsupervised input correlation-based learning (ICO). The neural CPG-based control creates insect-like gaits, while the AHN can continuously adapt robot joint movement individually with respect to the terrain during the stance phase using only the torque feedback. In parallel, the ICO generates short-term memory for proactive obstacle negotiation during the swing phase, allowing the posterior legs to step over the obstacle before hitting it. The control approach is evaluated on a bioinspired hexapod robot walking on complex unpredictable terrains (e.g., gravel, grass, and extreme random stepfield). The results show that the robot can successfully perform energy-efficient autonomous locomotion and online continuous adaptation with proactivity to overcome such terrains. Since our adaptive neural control approach does not require a robot model, it is general and can be applied to other bioinspired walking robots to achieve a similar adaptive, autonomous, and versatile function.
Linking Physical Activity to Breast Cancer via Sex Steroid Hormones, Part 2: The Effect of Sex Steroid Hormones on Breast Cancer Risk

We undertook a systematic review and appraised the evidence for an effect of circulating sex steroid hormones and sex hormone–binding globulin (SHBG) on breast cancer risk in pre- and postmenopausal women. Systematic searches identified prospective studies relevant to this review. Meta-analyses estimated breast cancer risk for women with the highest compared with the lowest level of sex hormones, and the DRMETA Stata package was used to graphically represent the shape of these associations. The ROBINS-E tool assessed risk of bias, and the GRADE system appraised the strength of evidence. In premenopausal women, there was little evidence that estrogens, progesterone, or SHBG were associated with breast cancer risk, whereas androgens showed a positive association. In postmenopausal women, higher estrogens and androgens were associated with an increase in breast cancer risk, whereas higher SHBG was inversely associated with risk. The strength of the evidence quality ranged from low to high for each hormone. Dose–response relationships between sex steroid hormone concentrations and breast cancer risk were most notable for postmenopausal women. These data support the plausibility of a role for sex steroid hormones in mediating the causal relationship between physical activity and the risk of breast cancer. See related reviews by Lynch et al., p. 11 and Swain et al., p. 16
Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations.
Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes

Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron‐dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis‐related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs‐based signature which could stratify patients with LUSC.
Prevalence and Associated Factors of Antenatal Anxiety Symptoms in Bangladesh: A Repeated Measures Cluster Data Analysis.

BACKGROUND Antenatal Anxiety affects the mothers and their child. Spontaneous abortion, preeclampsia, preterm birth, and low birth weight are the most common consequences. In Bangladesh, we have very limited understanding about the burden of antenatal anxiety and its associated factors. We conducted a prospective longitudinal study to estimate the prevalence of anxiety symptoms and identify associated factors in pregnant women. SUBJECTS AND METHODS A total of 1360 pregnant women were enrolled from 14 antenatal care (ANC) hospitals during September 2015 to August 2017. All selected women were assessed longitudinally at first, second and third trimesters of pregnancy. The State Anxiety Inventory (STAI-S) scale was used to measure the antenatal anxiety symptom. Generalize estimating equations (GEE) and alternating logistic regression (ALR) model were used to measure the risk factors and repetitive anxiety symptom measurements, respectively. RESULTS Over the study period, more than half (53.18%) of the women reported anxiety in at least one antenatal assessment. The prevalence of anxiety symptom in the first, second, and third trimesters was 29.5%, 23.5%, and 37.5%, respectively. Maternal anxiousness was significantly associated with the trimester, poor education, low blood hemoglobin, and low family income. CONCLUSION Women were at high risk of getting anxious during first and third trimesters of pregnancy. Findings of the study can be useful in developing and designing intervention to reduce anxiety in women during pregnancy.
Low mortality from COVID-19 at a nursing facility in France following a combined preventive and active treatment protocol.

BACKGROUND The aim of this study was to retrospectively describe the evolution of symptoms, infections, and mortality at a nursing facility in France that had implemented a protocol for the prevention and treatment of COVID-19. METHODS A database was created on 21 March 2020 to store all information related to residents, including co-morbidities, as well as COVID-19 symptoms, incidence, and mortality. Residents followed a COVID-19 protocol, consisting of preventive (administering vitamins and zinc, social distancing, and temperature checks) and active (antibiotics, anticoagulants, and corticosteroids) measures. RT-PCR and serology testing were performed on residents. A new coefficient, named the Zemgor coefficient, was calculated as the haemoglobin-to-albumin ratio at 2 time points 15 days apart, to monitor hypoxemia. RESULTS In January 2020, the nursing facility housed 192 residents, 75 men and 117 women, aged 80±11. One or more co-morbidities were present in 94% of residents, with the most common being dementia. The COVID-19 protocol provided 61% of residents with anticoagulants, 51%with antibiotics, 21% with oxygen therapy, and 3% with corticosteroids. The COVID-19 incidence was 51% based on presence of COVID-19 symptoms, 35% based on positive RT-PCR (amongst residents tested for RT-PCR) and 41% based on positive serology (amongst residents tested for serology), and the COVID-19 mortality rate was 8%. The Zemgor coefficient was 0.049±0.053 for patients with hypoxemia compared to 0.011±0.041 for patients without hypoxemia (P=0.001). CONCLUSIONS The protocol for the prevention and treatment of COVID-19 implemented at this nursing facility resulted in a COVID-19 incidence and mortality at the lower end of that reported by other nursing facilities.
Modified Medical Research Council and COPD Assessment Test Cutoff Points

BACKGROUND: The modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) are assessment instruments associated with level of physical activity of daily living (PADL) in patients with COPD. This study aimed to identify mMRC and CAT cutoff points to discriminate sedentary behavior and PADL level of subjects with COPD and verify whether these cutoff points differentiate pulmonary function, health-related quality of life (HRQOL), functional status, and mortality index in subjects with COPD. METHODS: Subjects (N = 131, FEV1: 36.7 ± 16.1% predicted) were assessed for lung function, mMRC, CAT, HRQOL, functional status, and mortality index. PADL was monitored using a triaxial accelerometer, and subjects were classified as sedentary/nonsedentary (cutoff point of 8.5 h/d in PADL < 1.5 metabolic equivalent of task [MET]), physically active/inactive (cutoff point of 80 min/d in PADL ≥ 3 METs), and with/without severe physical inactivity (cutoff point of 4,580 steps/d), according to variables provided by accelerometer. RESULTS: ROC curve indicated mMRC cutoff point of ≥ 2 (P < .05) for physical inactivity (sensitivity = 66%, specificity = 56%, AUC = 0.62), severe physical inactivity (sensitivity = 81%, specificity = 66%, AUC = 0.76), and sedentary behavior (sensitivity = 61%, specificity = 70%, AUC = 0.65). The identified CAT cutoff points were ≥ 16 and ≥ 20, considering severe physical inactivity (sensitivity = 76%, specificity = 54%, AUC = 0.69, P < .001) and sedentary behavior (sensitivity = 51%, specificity = 90%, AUC = 0.71, P = .001), respectively. Subjects who had mMRC ≥ 2 and CAT ≥ 16 or ≥ 20 presented worse pulmonary function, HRQOL, functional status, and mortality index compared with those who scored mMRC < 2 and CAT <16 or < 20. CONCLUSIONS: mMRC cutoff point of ≥ 2 is recommended to discriminate PADL level and sedentary behavior, whereas CAT cutoff points of ≥ 16 and ≥ 20 discriminated severe physical inactivity and sedentary behavior, respectively. These cutoff points differentiated subjects with COPD regarding all the outcomes assessed in this study.
Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration

Purpose The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model. Materials and Methods We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy. Results Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation. Conclusion Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.
The Significance of Interleukin-6 and Tumor Necrosis Factor-Alpha Levels in Cognitive Impairment among First-Ever Acute Ischaemic Stroke Patients.

BACKGROUND Acute ischemic stroke (AIS) frequently results in the development of cognitive impairment, which quite often persists. The pathophysiological mechanisms involved in the development of cognitive impairment are only partially elucidated. The aim of this study was to evaluate the correlation between interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) serum levels with cognitive impairment in AIS patients. SUBJECTS AND METHODS This hospital-based case-control study was performed during December 2014 - May 2018. A total number of 130 randomly selected patients were prospectively recruited from the Department of Neurology, Clinical Center University of Sarajevo. The study examined 100 first-ever AIS patients, while 30 comprised the non-stroke control group of patients with discogenic lumbosacral radiculopathy. All participants were evaluated using the Mini-Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery, and the Addenbrooke's Cognitive Examination-Revised. Cognitive testing and laboratory analyses were performed within the first three days of admission in all patients while AIS patients were reassessed on the 15thday of hospitalization. RESULTS Female stroke patients with cognitive impairment had significantly higher baseline levels of IL-6 (p<0.017), and TNF-α (p<0.017) than those without cognitive impairment. In the control measurement, a significant difference in IL-6 levels (p=0.037) in male and TNF-α levels (p=0.042) in female stroke patients with cognitive impairment was observed. CONCLUSIONS These findings indicate that pro-inflammatory cytokines are probably implicated in the pathogenesis of cognitive decline in AIS patients.
ALDH2 promotes uterine corpus endometrial carcinoma proliferation and construction of clinical survival prognostic model

UCEC is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. In our research, we explored the expression of the ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.
Somatic variant analysis suite: copy number variation clonal visualization online platform for large-scale single-cell genomics

The recent advance of single-cell copy number variation (CNV) analysis plays an essential role in addressing intratumor heterogeneity, identifying tumor subgroups and restoring tumor-evolving trajectories at single-cell scale. Informative visualization of copy number analysis results boosts productive scientific exploration, validation and sharing. Several single-cell analysis figures have the effectiveness of visualizations for understanding single-cell genomics in published articles and software packages. However, they almost lack real-time interaction, and it is hard to reproduce them. Moreover, existing tools are time-consuming and memory-intensive when they reach large-scale single-cell throughputs. We present an online visualization platform, single-cell Somatic Variant Analysis Suite (scSVAS), for real-time interactive single-cell genomics data visualization. scSVAS is specifically designed for large-scale single-cell genomic analysis that provides an arsenal of unique functionalities. After uploading the specified input files, scSVAS deploys the online interactive visualization automatically. Users may conduct scientific discoveries, share interactive visualizations and download high-quality publication-ready figures. scSVAS provides versatile utilities for managing, investigating, sharing and publishing single-cell CNV profiles. We envision this online platform will expedite the biological understanding of cancer clonal evolution in single-cell resolution. All visualizations are publicly hosted at https://sc.deepomics. org.
Optimal Tissue Reperfusion Estimation by Computed Tomography Perfusion Post-Thrombectomy in Acute Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion. However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI. Methods: We conducted a single-center retrospective analysis of patients with acute ischemic strokes who had endovascular therapy between 2018 and 2019. Computer tomography perfusion or magnetic resonance perfusion was performed before and after endovascular therapy. Tmax+6 volume reduction of >90% was defined as TOR. Comparisons of proportions of TOR in different grades of mTICI were performed. In the present study, the requirement for informed consents was waived. Results: Eighty-two patients were included. The difference in the proportion of TOR for TICI categories was statistically significant (mTICI score 0, 0%, mTICI score 2A, 0%, mTICI score 2b, 50.0%, mTICI score 2c, 80.0%, mTICI score 3, 81.3%, χ2=14.035, P=0.003). Multivariable logistic regression showed that lower age (odds ratio, 0.932, P=0.017), onset-to-tissue-type plasminogen activator time (odds ratio, 0.980, P=0.005) and TOR (odds ratio, 8.764, P=0.031) were associated with favorable functional outcome. Conclusions: The proportion of TOR achieved by mTICI score of 2b was significantly lower than mTICI score of 2c and mTICI score of 3. TOR was associated with favorable functional outcome, and the degree of reperfusion was more strongly correlated with outcomes than the mTICI scores.
Wearable Printed Temperature Sensors: Short Review on Latest Advances for Biomedical Applications

The rapid growth in wearable biosensing devices is driven by the strong desire to monitor the human health data and to predict the symptoms of chronic diseases at an early stage. Different sensors are developed for continuous monitoring of various biomarkers through wearable and implantable sensing patches. Temperature sensor has proved to be an important physiological parameter amongst the various wearable biosensing patches. This paper highlights the recent progresses made in printing of functional nanomaterials for developing wearable temperature sensors on polymeric substrates. A special focus is given to the advanced functional nanomaterials as well as their deposition through printing technologies. The geometric resolutions, shape, physical and electrical characteristics as well as sensing properties using different materials are compared and summarized. Wearability is the main concern of these newly developed sensors, which is summarized by discussing representative examples. Finally, the challenges concerning the stability, repeatability, reliability, sensitivity, linearity, ageing, and large-scale manufacturing are discussed with future outlook of the wearable systems.