Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer

Simple Summary A biomarker to predict survival is a critical need in pancreatic cancer treatment. We hypothesized that a four-gene score, which was previously reported to reflect cell proliferation, can be used as a predictive biomarker for pancreatic cancer. A total of 954 patients were analyzed for both discovery and validation of the four-gene score from publicly available datasets for pancreatic cancer, in order to investigate the relationship between the score and clinical features of pancreatic cancer, such as metastasis, cancer aggressiveness, immune cell infiltration, patient survival, and resectability. We found that the score correlated with clinical aggressiveness in pancreatic cancer, and did so to a higher degree compared to breast cancer cohorts. We found that the four-gene score identified poor survival in pancreatic cancer, and has potential as a predictive biomarker of treatment response in metastatic pancreatic cancer, as well completion of a pathologically complete (R0) resection. Appropriately utilized, the four-gene score could be a valuable prognostic and predictive tool for pancreatic cancer in the future. Abstract Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-β, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8+ T cell infiltration of tumors, but with high levels of interferon-γ and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.
Assault Deterrents and Educators’ Risk of Physical Assault: A Case–Control Study

The study purpose was to identify associations between assault deterrent presence in kindergarten through 12th (K–12) grade schools and physical assaults (PAs) against educators. Data collected through a two-phase study identified physical and nonphysical violent events and utilized a nested case–control study to identify PA risk/protective factors. Analyses included multivariable modeling. Adjusted analyses demonstrated a significant decreased risk of PA with routine locker searches (odds ratio [OR] = 0.49, 95% confidence interval [CI] [0.29, 0.82]). Also important, although not statistically significant, were presence of video monitors (OR = 0.72, 95% CI [0.50, 1.03]), intercoms (OR = 0.77, 95% CI [0.55, 1.06]), and required school uniforms/dress codes (OR = 0.74, 95% CI [0.52, 1.07]). These findings are integral to school nursing practice in which there is opportunity to influence application of relevant pilot intervention efforts as a first step in determining the potential efficacy of broad-based interventions that can positively impact the problem of school-related violence.
Absorption spectra and cyclic voltammograms of uranium species in molten lithium molybdate–sodium molybdate eutectic at 550 ºC

Abstract Absorption spectra of uranium species dissolved in molten lithium molybdate–sodium molybdate eutectic of 0.51Li2MoO4–0.49Na2MoO4 mixture at 550 ºC were measured by UV/Vis/NIR spectrophotometry, and their redox reactions were investigated by cyclic voltammetry. We found that the major ions of uranium species dissolved in the melt were uranyl penta-valent. After purging dry oxygen gas into the melt, penta-valent species were oxidized to the uranyl hexa-valent. In the cyclic voltammetry of the melt without uranium species, it was confirmed that the lithium-sodium molybdenum oxide compounds were deposited on the working electrode at the negative potential and the lithium molybdenum oxide compounds were deposited on the counter electrode at positive potential. When UO2 was dissolved into the melt, the reductive reaction of the uranium species was observed at the reductive potential of the pure melt. This suggests that the uranium species dissolved in the melts could be recovered as mixed uranium-molybdenum oxides by electrolysis.
Technologies for Pharmacogenomics: A Review

The continuous development of new genotyping technologies requires awareness of their potential advantages and limitations concerning utility for pharmacogenomics (PGx). In this review, we provide an overview of technologies that can be applied in PGx research and clinical practice. Most commonly used are single nucleotide variant (SNV) panels which contain a pre-selected panel of genetic variants. SNV panels offer a short turnaround time and straightforward interpretation, making them suitable for clinical practice. However, they are limited in their ability to assess rare and structural variants. Next-generation sequencing (NGS) and long-read sequencing are promising technologies for the field of PGx research. Both NGS and long-read sequencing often provide more data and more options with regard to deciphering structural and rare variants compared to SNV panels—in particular, in regard to the number of variants that can be identified, as well as the option for haplotype phasing. Nonetheless, while useful for research, not all sequencing data can be applied to clinical practice yet. Ultimately, selecting the right technology is not a matter of fact but a matter of choosing the right technique for the right problem.
NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data

Ionotropic GABA transmission is mediated by anion (mainly Cl−)-permeable GABAA receptors (GABAARs). In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl− by the Na-K-2Cl cotransporter NKCC1. While functional evidence firmly shows NKCC1-mediated ion transport in immature and diseased neurons, molecular detection of NKCC1 in the brain has turned out to be extremely difficult. In this review, we describe the highly inconsistent data that are available on the cell type-specific expression patterns of the NKCC1 mRNA and protein in the CNS. We discuss the major technical caveats, including a lack of knock-out-controlled immunohistochemistry in the forebrain, possible effects of alternative splicing on the binding of antibodies and RNA probes, and the wide expression of NKCC1 in different cell types, which make whole-tissue analyses of NKCC1 useless for studying its neuronal expression. We also review novel single-cell RNAseq data showing that most of the NKCC1 in the adult CNS may, in fact, be expressed in non-neuronal cells, especially in glia. As future directions, we suggest single-cell NKCC1 mRNA and protein analyses and the use of genetically tagged endogenous proteins or systematically designed novel antibodies, together with proper knock-out controls, for the visualization of endogenous NKCC1 in distinct brain cell types and their subcellular compartments.
Effect of a Long Exercise Program in the Reduction of Musculoskeletal Discomfort in Office Workers

The purpose of this study was to assess the effect of a six week exercise program to reduce the muscle tone of the trapezius and musculoskeletal discomfort (MED) of office workers. Twenty-six workers performed an exercise program based on: (1) stretching of cervical and/or dorsal region; (2) joint mobility of shoulders and rachis; (3) strengthening deep stabilizer and core muscles; and (4) scapula stabilizing exercises. A Myoton device was used to evaluate trapezius tone and the Cornell Musculoskeletal Discomfort Questionnaire was used to assess changes in MED at three points of evaluation: at the beginning (Pre_1) and at the end of the workday (Post_1), and after the training program (Pre_2). The Wilcoxon test and Cohen’s d were performed to examine differences and effect sizes between evaluations. Main results show that trapezius tone remained constant during the workday, but decreased in the dominant upper trapezius (p = 0.003, ES = −0.60) and increased in the non-dominant middle trapezius (p = 0.016, ES = 0.45) after the exercise program, which eliminated significant muscle asymmetries. MED significantly decreased in the neck (p = 0.027, ES = −0.60) and upper back (p = 0.046, ES = −0.67). In conclusion, MED appears to improve in office workers after a six week training program, which may be explained by a decrease in trapezius tone and increase in the left middle trapezius tone.
Anticancer Potential of Doxorubicin in Combination with GreenSynthesized Silver Nanoparticle and its Cytotoxicity Effects on CardioMyoblast Normal Cells.

BACKGROUND The use of DOX as an anticancer agent is associated with serious side effects on normal cells especially in cardiovascular tissue. OBJECTIVE Here, it was proposed suggested the combination of low dose of DOX with AgNPs provide ideal cytotoxicity against cancer cells and decrease side effects against normal human cells. This study evaluated evaluates the cytotoxic effects of green-synthetized AgNPs (GS-AgNPs) in combination with DOX in cancerous cells (MCF7) and investigated investigates its influences on cell growth and apoptosis in a normal cell line of heart (H9c2). METHODS We used of coffee extracts, as a reducing and stabilizing agent, for green-synthesis of AgNPs. GS-AgNPs were characterized by using various analytical methods. MTT assay was used for cell toxicity analysis in cancerous and normal cells. Moreover, Annexin-V /PI staining and mRNA expression of Bax, Bcl2 and p53 were performed for apoptosis measurement in heart normal cell line. RESULTS GS-AgNPs showed more biocompatibility for normal cells and higher cytotoxicity for cancerous cells compared to that reported for chemical synthesized nanoparticles. Our results also demonstrated that a selected combination of DOX and AgNPs, 20 µM AgNPs / 0.3 µM DOX, has a suitable cytotoxic effect against cancerous cells with a minimum toxic effect on normal cells. So, no significant alteration was observed in cell migration capacity, apoptosis and gene expression of BAX, Bcl-2 and P53 when H9c2 cells were treated with 20 µM AgNPs / 0.3 µM DOX relative to the non-treated control. CONCLUSION Finally, it seems that the combination of GS-AgNPs and DOX could be a potent strategy to combat cancer.
MicroRNA-139-5p upregulation is associated with diabetic endothelial cell dysfunction by targeting c-jun

Dysfunction of endothelial cells (ECs) and their progenitor cells is an important feature of diabetic vascular disease. MicroRNA (miR)-139-5p is involved in inhibiting the metastasis and progression of diverse malignancies. However, the role of miR-139-5p in ECs still remains unclarified. Here we demonstrated that miR-139-5p expression was elevated in endothelial colony-forming cells (ECFCs) isolated from patients with diabetes, ECs derived from the aorta of diabetic rodents, and human umbilical vein endothelial cells (HUVECs) cultured in high glucose media. MiR-139-5p mimics inhibited tube formation, migration, proliferation, and down-regulated expression of c-jun, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF)-B, in ECFCs and HUVECs, respectively; moreover, miR-139-5p inhibitors reversed the tendency. Further, gain- and-loss function experiments and ChIP assay indicated that miR-139-5p regulate functions of ECFCs by targeting c-jun-VEGF/PDGF-B pathway. In vivo experiments (Matrigel plug assay and hindlimb ischemia model) showed that miR-139-5p downregulation further promoted ECFC-mediated angiogenesis and blood perfusion. In conclusion, diabetes-mediated high miR-139-5p expression inhibits the c-jun-VEGF/PDGF-B pathway, thus decreasing ECFCs migration, tube formation and proliferation, which subsequently reduces ECs survival. Therefore, miR-139-5p might be an important therapeutic target in the treatment of diabetic vasculopathy in the future.
Guanine, a high-capacity and rapid-turnover nitrogen reserve in microalgal cells.

Nitrogen (N) is an essential macronutrient for microalgae, influencing their productivity, composition, and growth dynamics. Despite the dramatic consequences of N starvation, many free-living and endosymbiotic microalgae thrive in N-poor and N-fluctuating environments, giving rise to questions about the existence and nature of their long-term N reserves. Our understanding of these processes requires a unequivocal identification of the N reserves in microalgal cells as well as their turnover kinetics and subcellular localization. Herein, we identified crystalline guanine as the enigmatic large-capacity and rapid-turnover N reserve of microalgae. The identification was unambiguously supported by confocal Raman, fluorescence, and analytical transmission electron microscopies as well as stable isotope labeling. We discovered that the storing capacity for crystalline guanine by the marine dinoflagellate Amphidinium carterae was sufficient to support N requirements for several new generations. We determined that N reserves were rapidly accumulated from guanine available in the environment as well as biosynthesized from various N-containing nutrients. Storage of exogenic N in the form of crystalline guanine was found broadly distributed across taxonomically distant groups of microalgae from diverse habitats, from freshwater and marine free-living forms to endosymbiotic microalgae of reef-building corals (Acropora millepora, Euphyllia paraancora). We propose that crystalline guanine is the elusive N depot that mitigates the negative consequences of episodic N shortage. Guanine (C5H5N5O) may act similarly to cyanophycin (C10H19N5O5) granules in cyanobacteria. Considering the phytoplankton nitrogen pool size and dynamics, guanine is proposed to be an important storage form participating in the global N cycle.
PERCISTence: Strength or Stubbornness?

> History is the unfolding of miscalculation. > > —Barbara W. Tuchman, American historian In celebrating 60 years of JNM, it is hard to conceive of molecular imaging without 18F-FDG PET, particularly in oncology. Recognizing the importance of metabolic reprogramming in malignant transformation
Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse in HPV-Positive Women with Normal Cytology and Five-Year Type Concordance: A Randomized Comparison

Background: In human papillomavirus (HPV)-based cervical screening programs, management of HPV-positive women with normal cytology is debated. Longitudinal information on HPV type persistence may be employed for risk stratification. Methods: We assessed the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after repeatedly testing positive for the same HPV type(s) in the randomized population-based screening study Amsterdam (POBASCAM). We compared 18-month CIN3+ risks in HPV-positive women (intervention, n = 1,066) to those in HPV-positive/cytology-negative women who tested HPV-positive in the next screening round (control, n = 111) five years later, stratified for HPV type concordance. Results: The 18-month CIN3+ risk was 15% in HPV-positive women in the intervention group, 40% in the control group after two-round type concordance (relative risk 2.6, 95% confidence interval 1.9–3.4), and 20% in the control group after a type switch (1.3, 0.5–3.2). The relative increase in CIN3+ risk after two-round type concordance was similar in <35-year-old (3.0, 2.0–4.4) and older women (2.2, 1.4–3.5), and was high in high-risk HPV-positive women who were HPV16/18/31/33/45-negative in both rounds (9.9, 4.4–21.9). Conclusions: Five-year HPV type concordance signals high CIN3+ risk and warrants referral for colposcopy without additional cytology triage. Impact: HPV screening programs become highly efficient when HPV-positive women with negative triage testing at baseline are offered repeat HPV genotyping after five years.
Essential Role for FtsL in Activation of Septal Peptidoglycan Synthesis

A critical step in bacterial cytokinesis is the activation of septal peptidoglycan synthesis at the Z ring. Although FtsN is the trigger and acts through FtsQLB and FtsA to activate FtsWI the mechanism is unclear. ABSTRACT Spatiotemporal regulation of septal peptidoglycan (PG) synthesis is achieved by coupling assembly and activation of the synthetic enzymes (FtsWI) to the Z ring, a cytoskeletal element that is required for division in most bacteria. In Escherichia coli, the recruitment of the FtsWI complex is dependent upon the cytoplasmic domain of FtsL, a component of the conserved FtsQLB complex. Once assembled, FtsWI is activated by the arrival of FtsN, which acts through FtsQLB and FtsA, which are also essential for their recruitment. However, the mechanism of activation of FtsWI by FtsN is not clear. Here, we identify a region of FtsL that plays a key role in the activation of FtsWI which we designate AWI (activation of FtsWI) and present evidence that FtsL acts through FtsI. Our results suggest that FtsN switches FtsQLB from a recruitment complex to an activator with FtsL interacting with FtsI to activate FtsW. Since FtsQLB and FtsWI are widely conserved in bacteria, this mechanism is likely to be also widely conserved. IMPORTANCE A critical step in bacterial cytokinesis is the activation of septal peptidoglycan synthesis at the Z ring. Although FtsN is the trigger and acts through FtsQLB and FtsA to activate FtsWI the mechanism is unclear. Here, we find an essential role for FtsL in activating septal peptidoglycan (PG) synthesis and find that it acts on FtsI. Our results suggest a model where FtsWI is recruited in an inactive form by FtsQLB, and upon the arrival of FtsN, FtsQLB undergoes a conformational change so that a region of FtsL, which we designate the AWI domain, becomes available to interact with FtsI and activate the FtsWI complex. This mechanism for activation of the divisome has similarities to the activation of the elongasome and is likely to be widely conserved in bacteria.
Anxiety, Depression and Quality of Life in Older Adults: Trajectories of Influence across Age

This study focuses on the influence of anxiety and depression on individual trajectories of quality of life in old age through a longitudinal approach. A representative sample of adults aged 50+ living in Portugal and participating in wave 4 (W4) and wave 6 (W6) of the Survey of Health, Ageing and Retirement in Europe (SHARE) project was considered. Participants, 1765 at baseline (W4) and 1201 at follow up (W6), were asked about their quality of life (CASP-12) and emotional status (Euro-D scale; five items from the Beck Anxiety Inventory). Linear Mixed Effects models were performed to identify factors associated with changes in quality of life across age. Increasing age was found to have a significant negative effect on quality of life. Lower education and higher levels of depression and anxiety at baseline were also associated with worse quality of life; 42.1% of the variation of CASP-12 across age was explained by fixed and random effects, being depression followed by anxiety as the factors that presented with the highest relative importance. Both depression and anxiety play an important role in quality of life in older adults and must be acknowledged as important intervention domains to foster healthy and active aging.
D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.
DURIAN LEATHER: DEVELOPMENT, PROPERTIES AND STORAGE STABILITY

Three formulations of durian leather were developed and evaluated for their physicochemical, microbiological, sensory properties and storage stability. Proximate composition is reported. Vitamin C contents of the leather were relatively high and ranged between 21.6–26.6 mg/100 g. Water activity (Aw) of all formulations ranged between 0.57–0.62 and caloric content, 431–473 Kcal/100 g. After 12 weeks’ storage, all durian leather formulations were stable and showed low mold counts. The results from sensory evaluation revealed that the three formulations were acceptable in all attributes studied.
The role of the gut microbiome and diet in the pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with a prevalence that is increasing in parallel with the global rise in obesity and type 2 diabetes mellitus. The pathogenesis of NAFLD is complex and multifactorial, involving environmental, genetic and metabolic factors. The role of the diet and the gut microbiome is gaining interest as a significant factor in NAFLD pathogenesis. Dietary factors induce alterations in the composition of the gut microbiome (dysbiosis), commonly reflected by a reduction of the beneficial species and an increase in pathogenic microbiota. Due to the close relationship between the gut and liver, altering the gut microbiome can affect liver functions; promoting hepatic steatosis and inflammation. This review summarises the current evidence supporting an association between NAFLD and the gut microbiome and dietary factors. The review also explores potential underlying mechanisms underpinning these associations and whether manipulation of the gut microbiome is a potential therapeutic strategy to prevent or treat NAFLD.