Miracle-dz/UniFAR-FTUs huggingface dataset:
Prolonged stabilization of platinum-refractory ovarian cancer in a single patient undergoing long-term Mistletoe extract treatment

Rationale: Advanced ovarian malignancies are associated with poor overall survival; thus, patients often turn to alternative treatments, despite the controversy surrounding their use. Mistletoe extract has been commonly used as complementary medicine to treat patients with cancer for several decades, and has proven benefits in integrative oncology. Patient concerns: A 47-year-old woman with stage IVB ovarian cancer who underwent optimal surgical cytoreduction, but whose disease persisted after adjuvant platinum-based combination chemotherapy and 2nd-line chemotherapy. Diagnosis and interventions: The patient discontinued chemotherapy due to her septic condition and acute kidney injury accompanied by acute pyelonephritis, and opted for adjuvant treatment with mistletoe extract. Outcomes: The patient has achieved good health without progression of cancer or ascites over the 42 months since the 1st diagnosis and 24 months since the last relapse. Lessions: Our case suggests that mistletoe extract can produce favorable outcomes in patients with platinum-refractory ovarian cancer.
NBI-assisted digital flexible ureteroscopy in transitional renal cell carcinoma - an evidence-based assessment "through the looking glass" of the pathological analysis.

INTRODUCTION Digital flexible ureteroscopy (FURS) increasingly became a routine diagnostic procedure in upper urinary tract transitional cell carcinoma (UUT-TCC). Identifying elements that may suggest the malignant nature of a lesion and obtaining biopsy specimens sufficient for a reliable pathological analysis remain difficult challenges. Narrow-band imaging (NBI) technology appears to provide a more accurate observation of the upper tract urothelium. PATIENTS, MATERIALS AND METHODS During this prospective analysis, white light (WL) and NBI-assisted digital FURS were performed in 87 consecutive patients admitted for primary suspicion of UUT-TCC. The endoscopic technique comprised digital WL FURS, followed by the NBI assessment of the renal collecting system' mucosa. All suspicious areas of the pyelocaliceal urothelium were biopsied using the grasping forceps, separately for WL and NBI findings. RESULTS A total of 113 UUT-TCC tumors (104 pTa and nine carcinoma in situ - CIS) were confirmed by pathology in 62 patients. The patients' detection rate was significantly improved in NBI mode when compared to standard FURS (98.4% versus 91.9%, respectively), due to cases either exclusively diagnosed with UUT-TCC (8.1%) or presenting additional urothelial tumors (12.9%). Overall, 13 pTa and two CIS lesions were solely observed in NBI, which was on the other hand characterized by a significantly increased proportion of unnecessary biopsies (NBI versus WL rate of false-positive results - 17.5% versus 10.1%, respectively). CONCLUSIONS As additional tool for the standard WL evaluation of the pyelocaliceal system' urothelium, NBI-guided biopsies were emphasized as providing a significant diagnostic improvement during digital FURS.
Prediction of COPD and Related Events Improves by Combining Spirometry and the Single Breath Nitrogen Test

Abstract Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N2-slope). The N2-slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV1) to 25% among those with low FEV1, while increasing from 4% among those with the lowest N2-slope to 26% among those with the highest. However, combining the N2-slope and FEV1 resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N2-slope and lowest FEV1, and less than 1% among never smokers with the lowest N2-slope and highest FEV1. Thus, combining the results of the single breath N2-slope and FEV1 considerably improved the prediction of COPD events as compared to either test alone.
Cohort profile: the Prospective Research In Stress-Related Military Operations (PRISMO) study in the Dutch Armed Forces

Purpose The Prospective Research in Stress-Related Military Operations (PRISMO) study was initiated to gain a better understanding of the long-term impact of military deployment on mental health, and to map the different biological and psychological factors that contribute to the development of stress-related mental health symptoms. Participants The PRISMO cohort consists of a convenience sample of Dutch military personnel deployed to Afghanistan between 2005 and 2008. Baseline data collection resulted in the recruitment of 1032 military men and women. Combat troops as well as non-combat support troops were recruited to increase the representativeness of the sample to the population as a whole. Findings to date The prevalence of various mental health symptoms increases after deployment in PRISMO cohort members, but symptom progression over time appears to be specific for various mental health symptoms. For post-traumatic stress disorder, we found a short-term symptom increase within 6 months after deployment (8.2%), and a long-term symptom increase at 5 years after deployment (12.9%). Several biological vulnerability factors associated with the development of stress-related conditions after deployment were identified, including predeployment glucocorticoid receptor sensitivity and predeployment testosterone level. Thus far, 34 publications have resulted from the cohort. Future plans Various analyses are planned that will include the prevalence of mental health symptoms at 10 years postdeployment, as well as trajectory analyses that capture the longitudinal development of symptoms. Furthermore, we will use a machine learning approach to develop predictive and network models for several mental health symptoms, incorporating biological, psychological and social factors.
Activin‐A receptor expression patterns in prepubertal goat oocytes and derived embryos

This study examines the presence of activin IIA and IIB receptors (ActR-IIA and ActR-IIB) by Western blotting and immunocytochemistry in immature and IVM-oocytes, 2 to 8-cells embryos and blastocysts from prepubertal goats. Western blotting revealed that activin receptors are synthesized during oocyte maturation and embryo development. In the immunocytochemistry experiments, no immunostaining for either receptor was detected in oocytes while both receptors were immunolabelled in all the cells of cleaved embryos. In blastocysts, while ActR-IIA expression appeared evenly distributed in the two cell lineages, inner cell mass and trophectoderm, the ActR-IIB immunosignal was restricted mainly to the inner cell mass. Our findings reveal the presence of activin type II receptors (ActR-IIA and ActR-IIB) in in vitro matured prepubertal goat oocytes and blastocyst-stage embryos. The expression of these receptors could be a key factor in understanding differences between competent and incompetent oocytes.
Transcriptomic Analysis for Indica and Japonica Rice Varieties under Aluminum Toxicity

Aluminum (Al) at high concentrations inhibits root growth, damage root systems, and causes significant reductions in rice yields. Indica and Japonica rice have been cultivated in distinctly different ecological environments with different soil acidity levels; thus, they might have different mechanisms of Al-tolerance. In the present study, transcriptomic analysis in the root apex for Al-tolerance in the seedling stage was carried out within Al-tolerant and -sensitive varieties belonging to different subpopulations (i.e., Indica, Japonica, and mixed). We found that there were significant differences between the gene expression patterns of Indica Al-tolerant and Japonica Al-tolerant varieties, while the gene expression patterns of the Al-tolerant varieties in the mixed subgroup, which was inclined to Japonica, were similar to the Al-tolerant varieties in Japonica. Moreover, after further GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the transcriptomic data, we found that eight pathways, i.e., “Terpenoid backbone biosynthesis”, “Ribosome”, “Amino sugar and nucleotide sugar metabolism”, “Plant hormone signal transduction”, “TCA cycle”, “Synthesis and degradation of ketone bodies”, and “Butanoate metabolism” were found uniquely for Indica Al-tolerant varieties, while only one pathway (i.e., “Sulfur metabolism”) was found uniquely for Japonica Al-tolerant varieties. For Al-sensitive varieties, one identical pathway was found, both in Indica and Japonica. Three pathways were found uniquely in “Starch and sucrose metabolism”, “Metabolic pathway”, and “Amino sugar and nucleotide sugar metabolism”.
EEG-Based Control for Upper and Lower Limb Exoskeletons and Prostheses: A Systematic Review

Electroencephalography (EEG) signals have great impact on the development of assistive rehabilitation devices. These signals are used as a popular tool to investigate the functions and the behavior of the human motion in recent research. The study of EEG-based control of assistive devices is still in early stages. Although the EEG-based control of assistive devices has attracted a considerable level of attention over the last few years, few studies have been carried out to systematically review these studies, as a means of offering researchers and experts a comprehensive summary of the present, state-of-the-art EEG-based control techniques used for assistive technology. Therefore, this research has three main goals. The first aim is to systematically gather, summarize, evaluate and synthesize information regarding the accuracy and the value of previous research published in the literature between 2011 and 2018. The second goal is to extensively report on the holistic, experimental outcomes of this domain in relation to current research. It is systematically performed to provide a wealthy image and grounded evidence of the current state of research covering EEG-based control for assistive rehabilitation devices to all the experts and scientists. The third goal is to recognize the gap of knowledge that demands further investigation and to recommend directions for future research in this area.
A Standardized Phlorotannin Supplement Attenuates Caffeine-Induced Sleep Disruption in Mice

In our previous studies, a standardized phlorotannin (brown seaweed polyphenol) supplement (PS) exhibited sleep-promoting effects via type A γ-aminobutyric acid-benzodiazepine receptors in mice. In addition, in human clinical trials, it decreased wake after sleep onset in adults with sleep disturbance. In this follow-up study, we investigated whether PS attenuates caffeine-induced sleep disruption in mice. The effects of PS were evaluated in a caffeine model by analyzing sleep architecture based on electroencephalogram and electromyogram findings, and were compared with the effects of a well-known sedative-hypnotic drug zolpidem (ZPD). As expected, oral administration of caffeine (25 mg/kg) significantly increased sleep latency and decreased the amount of non-rapid eye movement sleep (NREMS). In the caffeine + PS and caffeine + ZPD groups, PS (500 mg/kg) attenuated caffeine-induced sleep disruption, and its effects were comparable with those of ZPD (10 mg/kg). In particular, PS inhibited the arousal effects of caffeine without change in delta activity during NREMS, whereas ZPD produced a decrease in the delta activity. Considering global trends in coffee and energy drink consumption, our finding suggest that PS may be useful to relieve transitory insomnia symptoms caused by caffeine consumption, unlike the prescription drug ZPD.
Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non‐nucleoside hepatitis B virus inhibitors by exploring the solvent‐exposed region

In continuation of our efforts toward the discovery of potent non‐nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent‐exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non‐nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti‐HBV DNA replication activity compared to lamivudine. In particular, compound II‐1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure–activity relationships of the new compounds were summarized, which may help in discovering more potent anti‐HBV agents via rational drug design.
Monte Carlo Analysis of Optical Interactions in Reflectance and Transmittance Finger Photoplethysmography

Photoplethysmography (PPG) is a non-invasive photometric technique that measures the volume changes in arterial blood. Recent studies have reported limitations in developing and optimising PPG-based sensing technologies due to unavailability of the fundamental information such as PPG-pathlength and penetration depth in a certain region of interest (ROI) in the human body. In this paper, a robust computational model of a dual wavelength PPG system was developed using Monte Carlo technique. A three-dimensional heterogeneous volume of a specific ROI (i.e., human finger) was exposed at the red (660 nm) and infrared (940 nm) wavelengths in the reflectance and transmittance modalities of PPG. The optical interactions with the individual pulsatile and non-pulsatile tissue-components were demonstrated and the optical parameters (e.g., pathlength, penetration depth, absorbance, reflectance and transmittance) were investigated. Results optimised the source-detector separation for a reflectance finger-PPG sensor. The analysis with the recorded absorbance, reflectance and transmittance confirmed the maximum and minimum impact of the dermis and bone tissue-layers, respectively, in the formation of a PPG signal. The results presented in the paper provide the necessary information to develop PPG-based transcutaneous sensors and to understand the origin of the ac and dc components of the PPG signal.
The risk of secondary cancer in pediatric medulloblastoma patients due to three-dimensional conformal radiotherapy and intensity-modulated radiotherapy.

BACKGROUND Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. The aim of this study was to estimate and compare the lifetime risk of radiation-induced secondary cancer in pediatric medulloblastoma patients using three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS 3D-CRT and IMRT plans were performed for 10 CSI pediatric patients. The average absorbed doses for organs at risk (OARs) was calculated from dose-volume histograms on the treatment planning system. The average lifetime risk of radiation-induced secondary cancer was then calculated. RESULTS Lifetime risk of secondary cancer for CSI pediatric patients treated using IMRT decreases in some OARs compared with those treated using 3D-CRT. This is attributable to the decrease in the average absorbed dose in some OARs when using IMRT technique. CONCLUSION Follow-up of medulloblastoma pediatric patients should be performed after ending the treatment course in order to diagnose early secondary tumors. IMRT technique is substantially better than 3D-CRT in terms of lifetime risk of radiation-induced secondary cancer, probably due to reduced dose to OARs especially to the thyroid, which is the most sensitive organ to radiation.
A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families

The triggering and development of Rheumatoid Arthritis (RA) is conditioned by environmental and genetic factors. Despite the identification of more than one hundred genetic variants associated with the disease, not all the cases can be explained. Here, we performed Whole Exome Sequencing in 9 multiplex families (N=30) to identify rare variants susceptible to play a role in the disease pathogenesis. We pre-selected 73 genes which carried rare variants with a complete segregation with RA in the studied families. Follow-up linkage and association analyses with pVAAST highlighted significant RA association of 24 genes (p-value < 0.05 after 106 permutations) and pinpointed their most likely causal variant. We re-sequenced the 10 most significant likely causal variants (p-value ≤ 0.019 after 106 permutations) in the extended pedigrees and 9 additional multiplex families (N=110). Only one SNV in SUPT20H, c.73T>A (p.Lys25*), presented a complete segregation with RA in an extended pedigree with early-onset cases. In summary, we identified in this study a new variant associated with RA in SUPT20H gene. This gene belongs to several biological pathways like macro-autophagy and monocyte/macrophage differentiation, which contribute to RA pathogenesis. In addition, these results showed that analyzing rare variants using a family-based approach is a strategy that allows to identify RA risk loci, even with a small dataset. Author summary Rheumatoid arthritis (RA) is one of the most frequent auto-immune disease in the world. It causes joint swellings and pains which can lead to mobility impairment. To date, the scientific community has identified a hundred genes carrying variants predisposing to RA, in addition to the major gene HLA-DRB1. However, they do not explain all cases of RA. By examining nine families with multiple RA cases, we identified a new rare nonsense variant in SUPT20H gene, c.73T>A (p.Lys25*). This finding is supported by the literature as the SUPT20H gene regulates several biological functions, such as macro-autophagy or monocyte/macrophage differentiation, that contribute to RA pathogenesis.
SCD1 methylation in subcutaneous adipose tissue associated with menopausal age

Abstract Objective: This study was designed to investigate associations between menopausal age and the DNA methylation levels of stearoyl-coenzyme A desaturase 1 (SCD1, selected by the Illumina Human Methylation 450 K Bead Chip) and explore the changes in mRNA levels of SCD1 and DNA methyltransferases (DNMTs) in response to estrogen replacement therapy (ERT). Methods: In the human experiment, we performed subcutaneous adipose tissue DNA extraction on 85 menopausal women. Methylation of SCD1 was measured by MethyLight polymerase chain reaction. In the rat experiment, we established models of menopause (ovariectomy group) and ERT (ovariectomy + 17β-estradiol group). The mRNA levels of SCD1, DNMT1, DNMT3A, and DNMT3B were determined. Results: The results showed that DNA methylation of SCD1 was inversely correlated with menopausal age (r = 0.370, P < 0.001). In the rat study, the mRNA levels of SCD1 decreased (P < 0.001) and those of DNMT3A (P < 0.001) and DNMT3B increased (P < 0.001) after ERT. Conclusion: Methylation levels of SCD1 were significantly associated with menopausal age. DNMT3A and DNMT3B may be involved in the methylation of SCD1.
Facets of Communication: Gap Junction Ultrastructure and Function in Cancer Stem Cells and Tumor Cells

Gap junction proteins are expressed in cancer stem cells and non-stem cancer cells of many tumors. As the morphology and assembly of gap junction channels are crucial for their function in intercellular communication, one focus of our review is to outline the data on gap junction plaque morphology available for cancer cells. Electron microscopic studies and freeze-fracture analyses on gap junction ultrastructure in cancer are summarized. As the presence of gap junctions is relevant in solid tumors, we exemplarily outline their role in glioblastomas and in breast cancer. These were also shown to contain cancer stem cells, which are an essential cause of tumor onset and of tumor transmission into metastases. For these processes, gap junctional communication was shown to be important and thus we summarize, how the expression of gap junction proteins and the resulting communication between cancer stem cells and their surrounding cells contributes to the dissemination of cancer stem cells via blood or lymphatic vessels. Based on their importance for tumors and metastases, future cancer-specific therapies are expected to address gap junction proteins. In turn, gap junctions also seem to contribute to the unattainability of cancer stem cells by certain treatments and might thus contribute to therapeutic resistance.
MS2 Labeling of Endogenous Beta-Actin mRNA Does Not Result in Stabilization of Degradation Intermediates

The binding of MS2 bacteriophage coat protein (MCP) to MS2 binding site (MBS) RNA stem-loop sequences has been widely used to label mRNA for live-cell imaging at single-molecule resolution. However, concerns have been raised recently from studies with budding yeast showing aberrant mRNA metabolism following the MS2-GFP labeling. To investigate the degradation pattern of MS2-GFP-labeled mRNA in mammalian cells and tissues, we used Northern blot analysis of β-actin mRNA extracted from the Actb-MBS knock-in and MBS×MCP hybrid mouse models. In the immortalized mouse embryonic cell lines and various organ tissues derived from the mouse models, we found no noticeable accumulation of decay products of β-actin mRNA compared with the wild-type mice. Our results suggest that accumulation of MBS RNA decay fragments does not always happen depending on the mRNA species and the model organisms used.
Applying Enhanced Recovery Pathways to Unique Patient Populations

Abstract Enhanced Recovery after Surgery (ERAS) pathways have become popular in colorectal surgery due to their associated decrease in length of stay (LOS), complications, and readmission rate. However, it is unclear if these pathways are safe, feasible, or effective in unique patient populations such as elderly patients, urgent/emergent surgeries, patients with specific comorbidities, inflammatory bowel disease, or pediatric patients. Enhanced recovery pathways appear safe in elderly patients, associated with decreased complications, though with slightly lower rates of adherence and increased LOS and readmission rates. Modified ERAS pathways have been applied to urgent and emergent surgeries, resulting in decreased morbidity and LOS. There have been no studies that performed subgroup analyses of ERAS pathways in patients with specific comorbidities. Studies investigating patients with inflammatory bowel disease on enhanced recovery pathways are extremely limited, but suggest that they are safe and feasible. Data on ERAS pathways in pediatric patients are still emerging. Therefore, though data are sparse, enhanced recovery pathways appear to be safe in unique patient populations, with similar efficacy in decreasing LOS and complications. There is an urgent need for more studies investigating these specific patient groups to aid perioperative decision making by colorectal surgeons.