Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic Effects of a Chalkophore, Methanobactin, on Microbial Methylation of Mercury

Some anaerobic microorganisms convert inorganic mercury (Hg) into the neurotoxin methylmercury, which can bioaccumulate and biomagnify in the food web. While the genetic basis of microbial mercury methylation is known, factors that control net methylmercury production in the environment are still poorly understood. Here, it is shown that mercury methylation can be substantially enhanced by one form of an exogenous copper-binding compound (methanobactin) produced by some methanotrophs, but not by another. This novel finding illustrates that complex interactions exist between microbes and that these interactions can potentially affect the net production of methylmercury in situ. ABSTRACT Microbial production of the neurotoxin methylmercury (MeHg) is a significant health and environmental concern, as it can bioaccumulate and biomagnify in the food web. A chalkophore or a copper-binding compound, termed methanobactin (MB), has been shown to form strong complexes with mercury [as Hg(II)] and also enables some methanotrophs to degrade MeHg. It is unknown, however, if Hg(II) binding with MB can also impede Hg(II) methylation by other microbes. Contrary to expectations, MB produced by the methanotroph Methylosinus trichosporium OB3b (OB3b-MB) enhanced the rate and efficiency of Hg(II) methylation more than that observed with thiol compounds (such as cysteine) by the mercury-methylating bacteria Desulfovibrio desulfuricans ND132 and Geobacter sulfurreducens PCA. Compared to no-MB controls, OB3b-MB decreased the rates of Hg(II) sorption and internalization, but increased methylation by 5- to 7-fold, suggesting that Hg(II) complexation with OB3b-MB facilitated exchange and internal transfer of Hg(II) to the HgcAB proteins required for methylation. Conversely, addition of excess amounts of OB3b-MB or a different form of MB from Methylocystis strain SB2 (SB2-MB) inhibited Hg(II) methylation, likely due to greater binding of Hg(II). Collectively, our results underscore the complex roles of microbial exogenous metal-scavenging compounds in controlling net production and bioaccumulation of MeHg in the environment. IMPORTANCE Some anaerobic microorganisms convert inorganic mercury (Hg) into the neurotoxin methylmercury, which can bioaccumulate and biomagnify in the food web. While the genetic basis of microbial mercury methylation is known, factors that control net methylmercury production in the environment are still poorly understood. Here, it is shown that mercury methylation can be substantially enhanced by one form of an exogenous copper-binding compound (methanobactin) produced by some methanotrophs, but not by another. This novel finding illustrates that complex interactions exist between microbes and that these interactions can potentially affect the net production of methylmercury in situ.
The Comparison of Detection Limits for Allergenic Foods between Total Adenylate (ATP+ADP+AMP) Hygiene Monitoring Test and Several Hygiene Monitoring Approaches.

Validation and verification of cleaning and inspection methods are essential in order to prevent the spread of allergens via cross-contact. Among the hygiene monitoring tests used onsite, the ATP test is rapid and provides quantifiable results. Nevertheless, since a wide variety of food contains significant amount of ADP and/or AMP due to the degradation of ATP, the ATP+ADP+AMP (A3) test is preferred for detecting food debris. Hence, the A3 test may be valuable in screening food debris that may contain residual allergens. In this study, the detection limits of the A3 test for 40 foods that are regulated in several countries as allergenic were compared to those of the other on-site used hygiene monitoring tests: the conventional ATP test with similar sensitivity for ATP, the protein swab test that detects as little as 50 mg protein, and the lateral flow immunoassay (LFI). The A3 test demonstrated lower detection limits than those of the ATP test. The detection sensitivity of the A3 test was greater than that of the protein swab test except for its use on gelatin (extracted protein). The cleaning validation performance using stainless steel model in fish and meat revealed that the A3 test is efficient in verifying the levels of remaining food debris. LFI displayed the best sensitivities for 10 of 14 foods; however, for some specific allergens, is not commercially available, but the A3 test can detect such food debris. Moreover, the detection limits of the A3 test were preferable or comparable to those of LFI for crustacean shellfish, and processed grains except for wheat flour and buckwheat. Undoubtedly, a field study in a food processing plant demonstrated that the amount of both A3 and milk protein (ELISA) considerably decreased as the cleaning steps progressed. Therefore, the A3 test is effective in detecting the risk for allergen cross-contact after inadequate cleaning.
Antihyperthermic treatment decreases perihematomal hypodensity

Objective To investigate the effect on perihematomal hypodensity and outcome of a decrease in body temperature in the first 24 hours in patients with intracerebral hemorrhage (ICH). Methods In this retrospective study on a prospectively registered database, among the 1,100 patients, 795 met all the inclusion criteria. Temperature variations in the first 24 hours and perihematomal hypodensity (PHHD) were recorded. Patients ≥37.5°C were treated with antihyperthermic drugs for at least 48 hours. The main objective was to determine the association among temperature variation, PHHD, and outcome at 3 months. Results The decrease in temperature in the first 24 hours increased the possibility of good outcome 11-fold. Temperature decrease, lower PHHD volume, and a good outcome were observed in 31.8% of the patients who received antihyperthermic treatment. Conclusion The administration of early antihyperthermic treatment in patients with spontaneous ICH with a basal axillary temperature ≥37.5°C resulted in good outcome in a third of the treated patients.
Novel Dual BET and PLK1 Inhibitor WNY0824 Exerts Potent Antitumor Effects in CRPC by Inhibiting Transcription Factor Function and Inducing Mitotic Abnormality

Castration-resistant prostate cancer (CRPC) is a lethal disease with few treatment alternatives once patients become resistant to second-generation antiandrogens. In CRPC, BET proteins are key regulators of AR- and MYC-mediated transcription, while the PLK1 inhibitor potentially downregulates AR and MYC besides influencing the cell cycle. Therefore, synchronous inhibition of BET and PLK1 would be a promising approach for CRPC therapy. This study developed a dual BET and PLK1 inhibitor WNY0824 with nanomolar and equipotent inhibition of BRD4 and PLK1. In vitro, WNY0824 exhibited excellent antiproliferation activity on AR-positive CRPC cells and induced apoptosis. These activities are attributable to its disruption of the AR-transcriptional program and the inhibition of the ETS pathway. Furthermore, WNY0824 downregulated MYC and induced mitotic abnormality. In vivo, oral WNY0824 administration suppressed tumor growth in the CRPC xenograft model of enzalutamide resistance. These findings suggest that WNY0824 is a selective dual BET and PLK1 inhibitor with potent anti-CRPC oncogenic activity and provides insights into the development of other novel dual BET- and PLK1-inhibiting drugs.
Enriching the science of homoeopathy

Hippocrates wrote about the cure of diseases by following the principle of ‘like with like’more than 2000 years ago, but it was formally systematised by Hahnemann through heroic experimentation on self, friends, family members and patients. He viewed health as a dynamic process tending to maintain a state of optimum equilibrium. Homoeopathic medicines are aimed to direct and stimulate the body’s self-regulatory mechanisms. The Homoeopathy emerged not in opposition to the biosciences but rather as a humane and relatively safe-model of medical practice at a time when ‘conventional’ medicine was both primitive and brutal in form, frequently lethal for patients. [1] It can be stated that Homeopathy was eventually born as a most scientifi c system, based solely on the concepts and methods derived from scientifi c experiments. Single-blind, placebo-control designs, used today by both contemporary and CAM systems, were fi rst put to biomedical use by Homoeopathy. [2]
Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.
RÔLE DE POLYMORPHISMES NUCLÉOTIDIQUES DANS LES GÈNESDE L’INTERLEUKINE-4 ET SON RÉCEPTEUR ET DU CORÉCEPTEURCD40, ET DES ALLÈLES HLA-DR, DANS LA PROGRESSION DE LAPOLYARTHRITE INFLAMMATOIRE D’INSTALLATION RÉCENTE

Jusqu’a 1% de la population canadienne est affectee par la polyarthrite rhumatoide, une maladie causant de la douleur, un handicap progressif, et des manifestations systemiques importantes. La progression tres heterogene de la polyarthrite rhumatoide et les effets secondaires graves associes a certains traitements mettent en valeur l’importance d’identifier des marqueurs pronostiques fiables permettant de predire la progression de la maladie chez les patients individuels. Ce projet de recherche visait a identifier des marqueurs immunogenetiques, specifiquement au niveau des genes HLA-DR, IL4, IL4R et CD40, associes a des issues particulieres de la maladie chez les patients de la cohorte EUPA, et s’insere dans un projet plus vaste explorant diverses avenues pour identifier des biomarqueurs pronostiques additionnels. Le genotypage des alleles HLA-DR des patients a ete effectue, et les patients ont ete tries selon la presence ou l'absence de deux epitopes d’interet, soient l'epitope partage (shared epitope) et l'epitope protecteur DERAA. Une technique de genotypage des polymorphismes nucleotidiques a ete developpee, validee, et appliquee. Enfin, des analyses statistiques ont etabli des correlations entre le genotype et diverses issues de la maladie. Nos resultats demontrent l’effet protecteur hautement significatif de l’epitope DERAA, present dans certains alleles HLA-DR chez nos patients. Nous demontrons aussi une association significative entre des alleles atypiques au niveau de polymorphismes dans IL4, IL4R et CD40 et des issues de la maladie, soient le dommage radiographique, a l’incapacite fonctionnelle, et a la probabilite d’entrer en remission chez les patients de la cohorte EUPA. Globalement, nous avons demontre l’importance du genotypage de ces marqueurs chez les patients atteints de polyarthrite inflammatoire d’inflammation recente, puisque les indices tires de ces typages fournissent de l’information additionnelle permettant aux cliniciens d’identifier les patients chez qui un traitement agressif serait benefique et, inversement, les patients qui pourraient etre epargnes des traitements plus agressifs. Nos donnees viennent s’ajouter a celles obtenues par les etudes effectuees dans le cadre des plusieurs autres volets de ce projet multi-institutionnel concernant les biomarqueurs pronostiques de la polyarthrite rhumatoide.
Cataract blindness in a Nigerian tertiary hospital- A one year review

Blindness negatively affects quality of life and le ads to increased mortality. Available community bas ed studies showed that three quarters of the causes of blindness majorly by cataract, is avoidable. This study was conducted so as to have hospital based da ta on cataract as a cause of blindness in University of Port Harcourt Teaching Hospital, (UPT H), Nigeria. The case records of all blind patient s (visual acuity of less than 3/60 or corresponding v isual field of less than 10 0 in the better eye with the best possible correction) presenting at the out pat ient clinic for year 2008 were reviewed. Of 214 patients, Cataract was responsible for about one th ird (n=82.38.3%). The age 40-60 years had the highest proportion of bilaterally cataract blind pa tients (40%). More males were bilaterally cataract blind (n=12.60%). Most bilaterally cataract blind patient s lived in the rural areas (n=12.60%). The uptake o f surgery was poorer among bilaterally cataract blind patients with only 30% (n=6) presenting for surger y. Cataract is a leading cause of blindness in the UPT H, Nigeria and is commoner in the older age group especially among males. The rural dwellers present late especially when bilaterally blind from catarac t. Subsidizing the costs may improve the uptake of ca taract surgery in our center.
T‐cell exhaustion interrelates with immune cytolytic activity to shape the inflamed tumor microenvironment

Direct quantification of exhausted T cells in human cancer is lacking, and its predictive value for checkpoint‐based treatment remains poorly investigated. We sought to systematically characterize the pan‐cancer landscape and molecular hallmarks of T‐cell dysfunction for the purpose of precision immunotherapy. Here, we defined a transcriptional signature for T‐cell exhaustion through analyzing differential gene expression between PD‐1‐high and PD‐1‐negative CD8+ T lymphocytes from primary non‐small cell lung cancer (NSCLC), followed by positive correlation tests with PDCD1 in TCGA lung carcinomas. A 78‐gene signature for exhausted CD8+ T cells (GET) was identified and validated to reflect dysfunctional immune state spanning different species and disease models. We discovered that GET estimation significantly correlated with intratumoral immune cytolytic activity (CYT) and T‐cell‐inflamed gene expression profile (GEP) across 30 solid tumor types. Miscellaneous tumor‐intrinsic and ‐extrinsic properties, in particular leukocyte proportions, genomic abnormalities, specific mutational signatures, and signaling pathways, were notably associated with GET levels. Furthermore, higher GET expression predicted an increased likelihood of clinical response to immune checkpoint inhibitors. These findings highlight the interrelation between T‐cell exhaustion and immune cytolytic activity at the pan‐cancer scale. The resulting inflamed tumor microenvironment may further crosstalk with other molecular and clinicopathological factors, which should be properly considered during immunotherapy biomarker development. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Temperament, Character, and Subjective Well-Being in Croatian War Veterans Suffering From Posttraumatic Stress Disorder

Abstract Subjective well-being is decreased in war-affected populations. However, no previous research has investigated the role of temperament and character dimensions in life satisfaction among war veterans with posttraumatic stress disorder (PTSD). This study enrolled 148 Croatian male war veterans being treated for combat-related PTSD. The participants completed the Beck Depression Inventory–Second Edition, Satisfaction with Life Scale, and Temperament and Character Inventory–Revised. Two multivariate regression analyses with life satisfaction as a dependent variable and temperament and character dimensions, respectively, as predictor variables, were performed. Temperament dimensions harm avoidance and novelty seeking as well as character dimensions self-directedness and cooperativeness were unique predictors of life satisfaction, while controlling for the influence of depressive symptoms, education level, and employment status. Given the influence of personality dimensions on life satisfaction, the routine assessment of these dimensions might help to establish the individually tailored treatment among war veterans with PTSD.
Sex Determination by Two Y-Linked Genes in Garden Asparagus[OPEN]

Y chromosome in garden asparagus determines sex via two Y-linked genes, one that suppresses female pistil development and another that promotes male anther development. The origin and early evolution of sex chromosomes have been hypothesized to involve the linkage of factors with antagonistic effects on male and female function. Garden asparagus (Asparagus officinalis) is an ideal species to investigate this hypothesis, as the X and Y chromosomes are cytologically homomorphic and evolved from an ancestral autosome pair in association with a shift from hermaphroditism to dioecy. Mutagenesis screens paired with single-molecule fluorescence in situ hybridization directly implicate Y-specific genes that respectively suppress female (pistil) development and are necessary for male (anther) development. Comparison of contiguous X and Y chromosome assemblies shows that hemizygosity underlies the loss of recombination between the genes suppressing female organogenesis (SUPPRESSOR OF FEMALE FUNCTION) and promoting male function (TAPETAL DEVELOPMENT AND FUNCTION1 [aspTDF1]). We also experimentally demonstrate the function of aspTDF1. These findings provide direct evidence that sex chromosomes can function through linkage of two sex determination genes.
Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.

BACKGROUND The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30). CONCLUSIONS Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
Consensus guidelines for managing the airway in patients with COVID‐19

Severe acute respiratory syndrome‐corona virus‐2, which causes coronavirus disease 2019 (COVID‐19), is highly contagious. Airway management of patients with COVID‐19 is high risk to staff and patients. We aimed to develop principles for airway management of patients with COVID‐19 to encourage safe, accurate and swift performance. This consensus statement has been brought together at short notice to advise on airway management for patients with COVID‐19, drawing on published literature and immediately available information from clinicians and experts. Recommendations on the prevention of contamination of healthcare workers, the choice of staff involved in airway management, the training required and the selection of equipment are discussed. The fundamental principles of airway management in these settings are described for: emergency tracheal intubation; predicted or unexpected difficult tracheal intubation; cardiac arrest; anaesthetic care; and tracheal extubation. We provide figures to support clinicians in safe airway management of patients with COVID‐19. The advice in this document is designed to be adapted in line with local workplace policies.
COVID-19 Global Pandemic: Options for Management of Gynecologic Cancers

Our world is facing a devastating crisis in the growing pandemic associated with the coronavirus (COVID-19) disease. As many nations take steps to implement strategies to contain the spread of this disease, we continue to see the tremendous impact this is having on the numerous healthcare workers who unite to overcome this tragic infection. We also recognize the concerns by both physicians and patients as it pertains to the management of patients diagnosed with cancer. We recognize that in this special situation we must continue to provide our gynecologic oncology patients with the highest quality of medical services and at the same time assure that we maximize the safety not only of our patients and their families but also of the medical staff and all associated teams that care for patients both in the inpatient and outpatient settings. To that end, the Editorial Team of the International Journal of Gynecological Cancer have compiled evidence-based data using established guidelines to propose strategies to optimize care of our patients while at the same time offering potential options to alleviate the burden to the healthcare system when resources may need to be diverted to the direct care of patients affected by the coronavirus (COVID-19) disease. Our proposal is intended as a tool for consideration and certainly not as a strategy for permanent change in patterns of practice. The goal is to share options, as gathered collectively by our team, in both the management and surveillance of patients diagnosed with gynecologic cancers during this time of global crisis.