Miracle-dz/UniFAR-FTUs huggingface dataset:
Arginase‐II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling

Elevated arginase type II (Arg‐II) associates with higher grade tumors. Its function and underlying molecular mechanisms in melanoma remain elusive. In the present study, we observed a significantly higher frequency of Arg‐II expression in melanoma of patients with metastasis than those without metastasis. Silencing Arg‐II in two human melanoma cell lines slowed down the cell growth, while overexpression of native but not a catalytically inactive Arg‐II promoted cell proliferation without affecting cell death. Treatment of cells with arginase inhibitor also reduced melanoma cell number, demonstrating that Arg‐II promotes melanoma cell proliferation dependently of its enzymatic activity. However, results from silencing Arg‐II or overexpressing native or the inactive Arg‐II as well as treatment with arginase inhibitor showed that Arg‐II promotes melanoma metastasis‐related processes, such as melanoma cell migration and adhesion on endothelial cells, independently of its enzymatic activity. Moreover, the treatment of the cells with STAT3 inhibitor suppressed Arg‐II‐promoted melanoma cell migration and adhesion. Furthermore, catalase, but not superoxide dismutase, prevented STAT3 activation as well as increased melanoma cell migration and adhesion induced by overexpressing native or the inactive Arg‐II. Taken together, our study uncovers both activity‐dependent and independent mechanisms of Arg‐II in promoting melanoma progression. While Arg‐II enhances melanoma cell proliferation through polyamine dependently of its enzymatic activity, it promotes metastasis‐related processes, that is, migration and adhesion onto endothelial cell, through mitochondrial H2O2‐STAT3 pathway independently of the enzymatic activity. Suppressing Arg‐II expression rather than inhibiting its enzymatic activity may, therefore, represent a novel strategy for the treatment of melanoma.
Validation of laboratory tests for infectious diseases in wild mammals: review and recommendations

Evaluation of the diagnostic sensitivity (DSe) and specificity (DSp) of tests for infectious diseases in wild animals is challenging, and some of the limitations may affect compliance with the OIE-recommended test validation pathway. We conducted a methodologic review of test validation studies for OIE-listed diseases in wild mammals published between 2008 and 2017 and focused on study design, statistical analysis, and reporting of results. Most published papers addressed Mycobacterium bovis infection in one or more wildlife species. Our review revealed limitations or missing information about sampled animals, identification criteria for positive and negative samples (case definition), representativeness of source and target populations, and species in the study, as well as information identifying animals sampled for calculations of DSe and DSp as naturally infected captive, free-ranging, or experimentally challenged animals. The deficiencies may have reflected omissions in reporting rather than design flaws, although lack of random sampling might have induced bias in estimates of DSe and DSp. We used case studies of validation of tests for hemorrhagic diseases in deer and white-nose syndrome in hibernating bats to demonstrate approaches for validation when new pathogen serotypes or genotypes are detected and diagnostic algorithms are changed, and how purposes of tests evolve together with the evolution of the pathogen after identification. We describe potential benefits of experimental challenge studies for obtaining DSe and DSp estimates, methods to maintain sample integrity, and Bayesian latent class models for statistical analysis. We make recommendations for improvements in future studies of detection test accuracy in wild mammals.
Depression and Anxiety in Hong Kong during COVID-19

It has been three months since the first confirmed case of coronavirus disease 2019 (COVID-19) in Hong Kong, and people now have a more complete picture of the extent of the pandemic. Therefore, it is time to evaluate the impacts of COVID-19 on mental health. The current population-based study aimed to evaluate the depression and anxiety of people in Hong Kong during the COVID-19 pandemic. Respondents were randomly recruited and asked to complete a structured questionnaire, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), the global rating of change scale and items related to COVID-19. Of the 500 respondents included in the study, 19% had depression (PHQ-9 score ≥ 10) and 14% had anxiety (GAD score ≥ 10). In addition, 25.4% reported that their mental health had deteriorated since the pandemic. Multiple logistic regression analysis found that not experiencing the SARS outbreak in 2003, being worried about being infected by COVID-19, being bothered by having not enough surgical masks and being bothered by not being able to work from home were associated with a poorer mental health status. Psychological support, such as brief, home-based psychological interventions, should be provided to citizens during the pandemic.
Synthesis, Modification and Characterization of Antimicrobial Textile Surface Containing ZnO Nanoparticles

In this research, a textile surface was modified by the sol–gel methodology with a new antimicrobial coating containing nanoparticles active against bacteria resistant to antibiotics. The effect of ultrasonic irradiation power (40 to 90 kHz), the concentration of reagents (nanoparticles, precursor and acids) and time (15 to 72 min) were investigated in relation to the structure, morphology and antimicrobial activity of coatings with zinc oxide nanoparticles. The relationship between the sonocatalytic performance and structure of the resultant modification was established by using various techniques, such as FTIR spectroscopy (FTIR) and scanning electron microscopy with an EDX detector (SEM-EDX), thin-layer chromatography (TLC) and antimicrobial effects were determined on selected model microorganisms. The homogeneity of layers with ZnO nanoparticles on samples was increased by increasing the ultrasonic irradiation power and time. The ultrasonic irradiation unify did not only unify both the structure and the morphology of samples, it also prevented the agglomeration of the nanoparticles. Moreover, under optimal conditions, an antimicrobial coating with ZnO nanoparticles, active against bacterial species S. aureus and E. coli was efficiently prepared. Results of the Time-kill methodology revieled excellent results starting after 6 hours of exposal to antimicrobialy functionalized cellulose polymer.
Cognitive profiles in persons with opioid use disorder enrolled in methadone treatment

Abstract Cognitive impairment is common in persons with opioid use disorder and associated with poor treatment outcomes, including elevated risk for relapse. Much less is known about the underlying structure of these deficits and the possible presence of cognitive phenotypes. A total of 177 adults (average 42.2 years of age, 52.0% male, 65.5% Caucasian) enrolled in a methadone maintenance treatment program completed the NIH Toolbox as part of a larger project. Cluster analyses revealed a 2-cluster solution–persons with intact cognitive function in all domains (n = 93; Intact) and those with impairments on tests of attention and executive function (n = 83; Impaired). Follow-up analyses revealed that the Impaired group was slightly older, more likely to self-identify as a racial/ethnic minority, and less likely to report consuming alcohol four or more times per week. These findings suggest the existence of distinct cognitive profiles in persons with opioid use disorder and encourage further examination, particularly studies to examine the possible benefits of routine screening for cognitive impairment as part of substance use treatment.
Comparison of Tissue-Based Molecular Markers in Younger versus Older Patients with Colorectal Neoplasia

Background: Emerging colorectal cancer trends demonstrate increased incidence and mortality in younger populations, prompting consideration of average-risk colorectal cancer screening initiation at age 45 versus 50 years. However, screening test performance characteristics in adults 45–49 years have been minimally described. To inform the biologic rationale for multi-target stool DNA (mt-sDNA) screening in younger patients, we analyzed and compared tissue levels of methylation (BMP3, NDRG4) and mutation (KRAS) markers included in the FDA-approved, mt-sDNA assay (Cologuard; Exact Sciences Corporation). Methods: Within 40–44, 45–49, and 50–64 year age groups, archived colorectal tissue specimens were identified for 211 sporadic colorectal cancer cases, 123 advanced precancerous lesions (APLs; adenomas >1 cm, high-grade dysplasia, ≥25% villous morphology, or sessile serrated polyp; 45–49 and 50–64 age groups only), and 204 histologically normal controls. Following DNA extraction, KRAS, BMP3, and NDRG4 were quantified using QuARTS assays, relative to ACTB (reference gene). Results: None of the molecular marker concentrations were significantly associated with age (P > 0.05 for all comparisons), with the exception of NDRG4 concentration in APL samples (higher in older vs. younger cases; P = 0.008). However, NDRG4 levels were also statistically higher in APL case versus normal control samples in both the 45–49 (P < 0.0001) and 50–64 (P < 0.0001) year age groups. Conclusions: Overall, these findings support the potential for earlier onset of average-risk colorectal cancer screening with the mt-sDNA assay. Impact: These novel data address an identified knowledge gap and strengthen the biologic basis for earlier-onset, average-risk screening with the mt-sDNA assay.
Systematic melittology: where to from here?

Those whose interest resides among the bees are truly fortunate. Among Hymenoptera, only the ants and some of the social wasps can boast of receiving comparable attention, but even these cannot compete if the full enormity of literature on the honey bee, specifically the western honey bee Apis mellifera L. , is taken into consideration. Naturally, this is not to say that bees as a whole have been studied evenly, as is more apparent when the same comparison is made between Apis and the remainder of the bees. Most work has gravitated to the conspicuously social lineages, to which Apis may be joined by its close relatives the bumble bees and stingless bees. Nonetheless, melittologists have a historical intensity of research, even excluding Apis, that is to be envied. In particular, a majestic, comprehensive and current account of the global supraspecific diversity is available (Michener, 2007), supplemented and enhanced by excellent regional treatments (e.g. Michener et al., 1994; Pauly et al., 2001; Silveira et al., 2002; Eardley et al., 2010). Such important guides, alongside annotated checklists for large regions or clades (e.g. Cardale, 1993; Gusenleitner & Schwarz, 2002; Moure et al., 2007; Ungricht et al., 2008; Ascher & Pickering, 2010; Eardley & Urban, 2010), render accessible a fauna that might otherwise be challenging to grasp. Hand-in-hand with these works has been a plethora of phylogenetic studies, rooted in a tradition of detailed comparative work, continually enhancing, expanding and revising the body of available data. Furthermore, bees are of such considerable biological interest and importance that melittological systematics has been enriched further by an organic synthesis with diverse and voluminous investigations into their behaviour, ecology and almost any conceivable aspect of their biology. It is no surprise then that bee phylogenetics is such a robust and active field. Hardly a season goes by without a
Floristic exchange between mainland Africa and Madagascar: case studies in Apocynaceae– Asclepiadoideae

The Apocynaceae–Asclepiadoideae (c. 125 species) of Madagascar's flora are highly endemic, and floristic conformity between Madagascar and Africa (and Asia) is low. Of the c. 1250 Old World Asclepiadoideae species, only ten species are shared between mainland Africa and Madagascar. Our comprehensive data elaborated during the last 15 years of systematic research in Asclepiadoideae were used to (1) examine Leroy's hypothesis that Madagascar's flora resulted from an autochthonous Gondwanean stock and natural introduction of taxa in time, (2) check the probability of our phylogentic considerations against the direction of the floristic exchange traced, and (3) present evidence for successful long‐distance dispersal events.
Cytokine Blood Filtration Responses in COVID-19

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.
Oviductal Extracellular Vesicles Improve Post-Thaw Sperm Function in Red Wolves and Cheetahs

Artificial insemination (AI) is a valuable tool for ex situ wildlife conservation, allowing the re-infusion and dissemination of genetic material, even after death of the donor. However, the application of AI to species conservation is still limited, due mainly to the poor survival of cryopreserved sperm. Recent work demonstrated that oviductal extracellular vesicles (oEVs) improved cat sperm motility and reduced premature acrosomal exocytosis. Here, we build on these findings by describing the protein content of dog and cat oEVs and investigating whether the incubation of cryopreserved red wolf and cheetah sperm with oEVs during thawing improves sperm function. Both red wolf and cheetah sperm thawed with dog and cat oEVs, respectively, had more intact acrosomes than the non-EV controls. Moreover, red wolf sperm thawed in the presence of dog oEVs better maintained sperm motility over time (>15%) though such an improvement was not observed in cheetah sperm. Our work demonstrates that dog and cat oEVs carry proteins important for sperm function and improve post-thaw motility and/or acrosome integrity of red wolf and cheetah sperm in vitro. The findings show how oEVs can be a valuable tool for improving the success of AI with cryopreserved sperm in threatened species.
Resting-state network dysconnectivity in ADHD: A system-neuroscience-based meta-analysis

Abstract Objectives Neuroimaging studies report altered resting-state functional connectivity in attention deficit/hyperactivity disorder (ADHD) across multiple brain systems. However, there is inconsistency among individual studies. Methods We meta-analyzed seed-based resting state studies of ADHD connectivity within and between four established resting state brain networks (default mode, cognitive control, salience, affective/motivational) using Multilevel Kernel Density Analysis method. Results Twenty studies with 944 ADHD patients and 1121 controls were included in the analysis. Compared to controls, ADHD was associated with disrupted within-default mode network (DMN) connectivity – reduced in the core (i.e. posterior cingulate cortex seed) but elevated in the dorsal medial prefrontal cortex sub-system (i.e. temporal pole-inferior frontal gyrus). Connectivity was elevated between nodes in the cognitive control system. When the analysis was restricted to children and adolescents, additional reduced connectivity was detected between DMN and cognitive control and affective/motivational and salience networks. Conclusions Our data are consistent with the hypothesis that paediatric ADHD is a DMN-dysconnectivity disorder with reduced connectivity both within the core DMN sub-system and between that system and a broad set of nodes in systems involved in cognition and motivation.
A Machine-learning Approach for the Assessment of the Proliferative Compartment of Solid Tumors on Hematoxylin-Eosin-Stained Sections

We introduce a machine learning-based analysis to predict the immunohistochemical (IHC) labeling index for the cell proliferation marker Ki67/MIB1 on cancer tissues based on morphometrical features extracted from hematoxylin and eosin (H&E)-stained formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. We provided a proof-of-concept prediction of the Ki67/MIB1 IHC positivity of cancer cells through the definition and quantitation of single nuclear features. In the first instance, we set our digital framework on Ki67/MIB1-stained OSCC (oral squamous cell carcinoma) tissue sample whole slide images, using QuPath as a working platform and its integrated algorithms, and we built a classifier in order to distinguish tumor and stroma classes and, within them, Ki67-positive and Ki67-negative cells; then, we sorted the morphometric features of tumor cells related to their Ki67 IHC status. Among the evaluated features, nuclear hematoxylin mean optical density (NHMOD) presented as the best one to distinguish Ki67/MIB1 positive from negative cells. We confirmed our findings in a single-cell level analysis of H&E staining on Ki67-immunostained/H&E-decolored tissue samples. Finally, we tested our digital framework on a case series of oral squamous cell carcinomas (OSCC), arranged in tissue microarrays; we selected two consecutive sections of each OSCC FFPE TMA (tissue microarray) block, respectively stained with H&E and immuno-stained for Ki67/MIB1. We automatically detected tumor cells in H&E slides and generated a “false color map” (FCM) based on NHMOD through the QuPath measurements map tool. FCM nearly coincided with the actual immunohistochemical result, allowing the prediction of Ki67/MIB1 positive cells in a direct visual fashion. Our proposed approach provides the pathologist with a fast method of identifying the proliferating compartment of the tumor through a quantitative assessment of the nuclear features on H&E slides, readily appreciable by visual inspection. Although this technique needs to be fine-tuned and tested on larger series of tumors, the digital analysis approach appears to be a promising tool to quickly forecast the tumor’s proliferation fraction directly on routinely H&E-stained digital sections.
Evaluating the nutrient status and fertilization response potential of planted spruce in the interior of British Columbia

Factorial combinations of nitrogen (0, 100, and 200 kg/ha) and a "complete" fertilizer (0 and 1170 kg/ha) were applied to 10 spruce (Piceaglauca (Moench) Voss and hybrids) plantations in the central interior of British Columbia. Postfertilization patterns of foliar nutrient concentration and needle weight were used to evaluate the nutrient status and fertilization response potential of treated stands. When applied alone, N and the complete fertilizer generally had little effect on the weight of needles produced in the first year after treatment. Combined applications, however, often resulted in large responses. In 8 of the 10 installations, combined applications of N + complete fertilizer were significantly more effective than N alone in stimulating first-year needle weight. Which nutrient in the complete fertilizer is responsible for the increased needle-weight response cannot be stated conclusively. However, examination of foliar nutrient concentration data, combined with graphical analyses of relative .
Biocatalytic Production of a Potent Inhibitor of Adipocyte Differentiation from Phloretin Using Engineered CYP102A1.

In this study, we investigated an efficient enzymatic strategy for producing potentially valuable phloretin metabolites from phlorizin, a glucoside of phloretin that is rich in apple pomace. Almond β-glucosidase efficiently removed phlorizin's glucose moiety to produce phloretin. CYP102A1 engineered by site-directed mutagenesis, domain swapping, and random mutagenesis catalysed the highly regioselective C-hydroxylation of phloretin into 3-OH phloretin with high conversion yields. Under the optimal hydroxylation conditions of 15 g cells L-1 and a 20 mM substrate for whole-cell biocatalysis, phloretin was regioselectively hydroxylated into 3.1 mM 3-OH phloretin each hour. Furthermore, differentiating 3T3-L1 preadipocytes into adipocytes and lipid accumulation was dramatically inhibited by 3-OH phloretin but promoted by phloretin. Consistent with these inhibitory effects, the expression of adipogenic regulator genes was downregulated by 3-OH phloretin. We propose a platform for the sustainable production and value creation of phloretin metabolites from apple pomace capable of inhibiting adipogenesis.
Factors associated with loss to follow-up of outpatients with depression in general hospitals

Objective We aimed to understand the reasons behind outpatient loss to follow-up and the views of Chinese patients with depression regarding disease diagnosis and antidepressant therapy. Methods Consecutive outpatients with newly diagnosed depressive disorder between September 2012 and August 2013 at the Shanghai First People’s Hospital (a tertiary hospital) were categorized into follow-up and lost-to-follow-up groups. We collected information on demographics, the Hamilton depression (HAMD) scale, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale, and Symptom Checklist-90. Patients were routinely followed at 2, 4, 8, and 12 weeks. Any missed appointment was considered lost to follow-up. Results After 12 weeks of treatment, only 42.2% (70/166) of patients were continuing follow-up. Patients lost to follow-up were significantly younger (median, 42.5 vs. 56.5 years), had different marital status, higher education level, higher SDS score (43.8 ± 10.8 vs. 40.2 ± 10.9), and higher HAMD score (median, 21 vs. 19). Age (odds ratio (OR) = 0.97, 95% confidence interval (CI): 0.95–0.997), and HAMD score (OR = 1.14, 95% CI: 1.01–1.29) were independently associated with loss to follow-up. Conclusion Young age, higher HAMD score, and poor knowledge of depression and treatment were the main factors associated with loss to follow-up during depression management among our Chinese patients.
Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease

Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non‐alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity.