Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing non‐melanoma skin cancer risk in renal transplant recipients

With an increasing number of renal transplant recipients (RTRs) and improving patient survival, a higher incidence of non‐melanoma skin cancer (NMSC) has been observed. NMSC in RTRs are often more numerous and biologically more aggressive than the general population, thus contributing towards an increase in morbidity and to a lesser degree, mortality. The resultant cumulative health and financial burden is a recognized concern. Proposed strategies in mitigating risks of developing NMSC and early therapeutic options thereof include tailored modification of immunosuppressants in conjunction with sun protection in all transplant patients. This review highlights the clinical and financial burden of transplant‐associated skin cancers, carcinogenic mechanisms in association with immunosuppression, importance of skin cancer awareness campaign and integrated transplant skin clinic, and the potential role of chemoprotective agents. A scheme is proposed for primary and secondary prevention of NMSC based on the available evidence.
Virus-associated disruption of mucosal epithelial tight junctions and its role in viral transmission and spread

ABSTRACT Oropharyngeal, airway, intestinal, and genital mucosal epithelia are the main portals of entry for the majority of human pathogenic viruses. To initiate systemic infection, viruses must first be transmitted across the mucosal epithelium and then spread across the body. However, mucosal epithelia have well-developed tight junctions, which have a strong barrier function that plays a critical role in preventing the spread and dissemination of viral pathogens. Viruses can overcome these barriers by disrupting the tight junctions of mucosal epithelia, which facilitate paracellular viral penetration and initiate systemic disease. Disruption of tight and adherens junctions may also release the sequestered viral receptors within the junctional areas, and liberation of hidden receptors may facilitate viral infection of mucosal epithelia. This review focuses on possible molecular mechanisms of virus-associated disruption of mucosal epithelial junctions and its role in transmucosal viral transmission and spread.
Addressing anaemia in pregnancy in rural plains Nepal: A qualitative, formative study

Abstract Maternal anaemia prevalence in low‐income countries is unacceptably high. Our research explored the individual‐, family‐ and community‐level factors affecting antenatal care uptake, iron folic acid (IFA) intake and consumption of micronutrient‐rich diets among pregnant women in the plains of Nepal. We discuss how these findings informed the development of a home visit and community mobilisation intervention to reduce anaemia in pregnancy. We used a qualitative methodology informed by the socio‐ecological framework, conducting semi‐structured interviews with recently pregnant women and key informants, and focus group discussions with mothers‐in‐law and fathers. We found that harmful gender norms restricted women's access to nutrient‐rich food, restricted their mobility and access to antenatal care. These norms also restricted fathers' role to that of the provider, as opposed to the caregiver. Pregnant women, mothers‐in‐law and fathers lacked awareness about iron‐rich foods and how to manage the side effects of IFA. Fathers lacked trust in government health facilities affecting access to care and trust in the efficacy of IFA. Our research informed interventions by (1) informing the development of intervention tools and training; (2) informing the intervention focus to engaging mothers‐in‐law and men to enable behaviour change; and (3) demonstrating the need to work in synergy across individual, family and community levels to address power and positionality, gender norms, trust in health services and harmful norms. Participatory groups and home visits will enable the development and implementation of feasible and acceptable strategies to address family and contextual issues generating knowledge and an enabling environment for behaviour change.
The multi-functional reovirus σ3 protein is a virulence factor that suppresses stress granule formation and is associated with myocardial injury

The mammalian orthoreovirus double-stranded (ds) RNA-binding protein σ3 is a multifunctional protein that promotes viral protein synthesis and facilitates viral entry and assembly. The dsRNA-binding capacity of σ3 correlates with its capacity to prevent dsRNA-mediated activation of protein kinase R (PKR). However, the effect of σ3 binding to dsRNA during viral infection is largely unknown. To identify functions of σ3 dsRNA-binding activity during reovirus infection, we engineered a panel of thirteen σ3 mutants and screened them for the capacity to bind dsRNA. Six mutants were defective in dsRNA binding, and mutations in these constructs cluster in a putative dsRNA-binding region on the surface of σ3. Two recombinant viruses expressing these σ3 dsRNA-binding mutants, K287T and R296T, display strikingly different phenotypes. In a cell-type dependent manner, K287T, but not R296T, replicates less efficiently than wild-type (WT) virus. In cells in which K287T virus demonstrates a replication deficit, PKR activation occurs and abundant stress granules (SGs) are formed at late times post-infection. In contrast, the R296T virus retains the capacity to suppress activation of PKR and does not mediate formation of SGs at late times post-infection. These findings indicate that σ3 inhibits PKR independently of its capacity to bind dsRNA. In infected mice, K287T produces lower viral titers in the spleen, liver, lungs, and heart relative to WT or R296T. Moreover, mice inoculated with WT or R296T viruses develop myocarditis, whereas those inoculated with K287T do not. Overall, our results indicate that σ3 functions to suppress PKR activation and subsequent SG formation during viral infection and that these functions correlate with virulence in mice.
Association between thyroid hormone levels and frailty in an older inpatient cohort: a cross-sectional study.

BACKGROUND Frailty is a common biological syndrome in elderly people, and the aging process regulates thyroid function. The present study aimed to determine the prevalence of frailty in an older inpatient cohort using the FRAIL scale and to evaluate the association of frailty with thyroid hormone levels. METHODS This cross-sectional study was performed in the Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China. From November 2019 to April 2020, 146 inpatients aged ≥65 years were recruited for the study and demographic data, frailty, geriatric assessment, and thyroid hormone levels were evaluated. Frailty was determined by the FRAIL scale, and geriatric assessment was based on activities of daily living (ADL) and instrumental activities of daily living (IADL). The data were analyzed using appropriate parametric and nonparametric statistical tests. RESULTS At enrollment, 31 (21.23%) of the total participants were robust, 31 (21.23%) were pre-frail, and 84 (57.53%) were frail. The frail patients were significantly older than the robust patients and pre-frail patients (P<0.001 for both). The percentages of ADL disability differed significantly among the patients for frail versus robust, frail versus pre-frail, and pre-frail versus robust, as did the percentages of IADL disability among patients for frail versus robust and frail versus pre-frail (P<0.01 for all). In binary logistic regression analyses adjusted for age, sex, body mass index, HbA1c (%), and smoking, frailty was significantly associated with serum thyroid stimulating hormone (TSH) concentration [odds ratio (OR): 1.704], T3 concentration (OR: 0.102), ADL score (OR: 0.793), and IADL score (OR: 0.413). CONCLUSIONS In our study population, the prevalence of frailty was higher in older geriatric inpatients in China than other studies. Inpatients with high TSH levels were at increased risk of frailty. Conduction of future longitudinal studies is warranted to determine the relationship between thyroid hormone levels and frailty.
Antimicrobial resistance of the enteric protozoon Giardia duodenalis – A narrative review

Introduction As therapy-refractory giardiasis is an emerging health issue, this review aimed at summarizing mechanisms of reduced antimicrobial susceptibility in Giardia duodenalis and strategies to overcome this problem. Methods A narrative review on antimicrobial resistance in G. duodenalis was based upon a selective literature research. Results Failed therapeutic success has been observed for all standard therapies of giardiasis comprising nitroimidazoles like metronidazole or tinidazole as first line substances but also benznidazoles like albendazole and mebendazole, the nitrofuran furazolidone, the thiazolide nitazoxanide, and the aminoglycoside paromomycin. Multicausality of the resistance phenotypes has been described, with differentiated gene expression due to epigenetic and post-translational modifications playing a considerable bigger role than mutational base exchanges in the parasite DNA. Standardized resistance testing algorithms are not available and clinical evidence for salvage therapies is scarce in spite of research efforts targeting new giardicidal drugs. Conclusion In case of therapeutic failure of first line nitroimidazoles, salvage strategies including various options for combination therapy exist in spite of limited evidence and lacking routine diagnostic-compatible assays for antimicrobial susceptibility testing in G. duodenalis. Sufficiently powered clinical and diagnostic studies are needed to overcome both the lacking evidence regarding salvage therapy and the diagnostic neglect of antimicrobial resistance.
A standard of care for individuals with PIK3CA‐related disorders: An international expert consensus statement

Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous entities have been grouped as PIK3CA‐Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low‐level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient‐specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi‐system and often complex medical issues seen with PROS. In March 2019, macrocephaly‐capillary malformation (M‐CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M‐CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge.
Metabolic surgery in China: present and future

Abstract Obesity and its related complications comprise a serious public health problem worldwide, and obesity is increasing in China. Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications. The pathogenesis of obesity is complex and not yet fully understood. Here, we review the current efficacy and safety of metabolic surgery, as well as recent progress in mechanistic studies and surgical procedures in China. The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.
Effect of the ratio of vessel-specific volume to fractional myocardial mass on fractional flow reserve

This study aimed to examine whether the ratio of vessel-specific coronary arterial lumen volume to the fraction of myocardial mass (VR/MR) affects myocardial ischemia. We proposed a calculation method for VR/MR, and compared the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) with VR/MR in predicting myocardial ischemia. VR/MR and V/M were computed using data from 205 patients with 241 stenosis vessel who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography, and fractional flow reserve. The vessel-specific coronary arterial lumen volume (VR) was obtained from CTA by segmenting the coronary arterial lumen volume, while the vessel-specific fraction of myocardial mass (MR) was obtained by allometric scaling. The VR/MR was then calculated. The cut-off values of V/M (23.55 mm3/g) and VR/MR (12.98 mm3/g) were used to define equal groups of ischemic and non-ischemic patients, respectively. Using these cut-off values, the accuracy, specificity, sensitivity, positive predictive value, and negative predictive value of V/M were 60%, 76%, 45%, 57%, and 66%, and of VR/MR were 87%, 92%, 77%, 89%, and 83%, respectively. Patients have different VR/MR values in different stenotic coronary arteries. Clinically, VR/MR is a quantitative indicator of the risk of myocardial ischemia.
Three in One: The Versatility of Hydrogen Bonding Interaction in Halide Salts with Hydroxy‐Functionalized Pyridinium Cations

Abstract The paradigm of supramolecular chemistry relies on the delicate balance of noncovalent forces. Here we present a systematic approach for controlling the structural versatility of halide salts by the nature of hydrogen bonding interactions. We synthesized halide salts with hydroxy‐functionalized pyridinium cations [HOC n Py]+ (n=2, 3, 4) and chloride, bromide and iodide anions, which are typically used as precursor material for synthesizing ionic liquids by anion metathesis reaction. The X‐ray structures of these omnium halides show two types of hydrogen bonding: ‘intra‐ionic’ H‐bonds, wherein the anion interacts with the hydroxy group and the positively charged ring at the same cation, and ‘inter‐ionic’ H‐bonds, wherein the anion also interacts with the hydroxy group and the ring system but of different cations. We show that hydrogen bonding is controllable by the length of the hydroxyalkyl chain and the interaction strength of the anion. Some molten halide salts exhibit a third type of hydrogen bonding. IR spectra reveal elusive H‐bonds between the OH groups of cations, showing interaction between ions of like charge. They are formed despite the repulsive interaction between the like‐charged ions and compete with the favored cation‐anion H‐bonds. All types of H‐bonding are analyzed by quantum chemical methods and the natural bond orbital approach, emphasizing the importance of charge transfer in these interactions. For simple omnium salts, we evidenced three distinct types of hydrogen bonds: Three in one!
Effects of small size-fractionated fish protein hydrolysate substitution of fish meal in high plant protein diets on the growth performance and non-specific immunity of Japanese flounder,Paralichthys olivaceus

A 63-day feeding experiment was conducted to evaluate the effects of fish protein hydrolysate as feed ingredient in high plant-protein diets on growth performance and non-specific immunity for Japanese flounder,Paralichthys olivaceus.Fish protein hydrolysates respectively replaced 0(FM1,negative control,containing 55% soybean meal and 19% fish meal),0(FM2,positive control,containing 45% soybean meal and 25% fish meal),6%(FPH6),11%(FPH11),16%(FPH16),21%(FPH21),and 26%(FPH26)of the total protein.The results showed that specific growth rate and protein retention of fish fed with FPH11 was significantly higher than FM1(P0.05),but was not significantly different from FM2(P0.05). For protein digestibility,all the hydrolyzed protein diets were significantly higher than FM1(P0.05),but was not significantly different from FM2(P0.05). Feeding rates of FPH11,FPH16,FPH21 and FPH26 were significantly higher than FM2(P0.05). The relative activities of acid phosphatase(ACP) in fish fed with FM1 was significantly lower than FPH26(P0.05). SOD relative activities in all the hydrolyzed protein diet were higher than FM1(P0.05),and SOD relative activities in FPH11 was significantly higher than FM2(P0.05). Total antioxidative capacity of FPH6,FPH11and FPH16 were significantly higher than FM1 and lower than FM2(P0.05).
Efficacy of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND There is a close relationship between cardiovascular risk factors and polycystic ovary syndrome (PCOS), and omega-3 fatty acids may have a key role in improving cardiovascular risk factors. We conducted the current systematic review and meta-analysis to evaluate the effect of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with PCOS. METHODS We searched 4 databases including PubMed (MEDLINE), Cochrane Library, Embase, and Web of Science from inception to February 2021. We included randomized controlled trials (RCTs) that reported the effects of omega-3 fatty acid treatment for PCOS. According to the Cochrane system evaluation guide manual, 2 researchers independently assessed the methodological quality of the included studies. We pooled results using either a fixed effect model or random effect model. RESULTS We identified 314 articles, of which 10 met the criteria for inclusion, involving 778 participants. The pooled results suggested an association between the supplementation of omega-3 fatty acids and a reduction in serum insulin [-2.58 pmol/L, 95% confidence interval (CI): -3.34 to -1.82 pmol/L, P<0.00001, I2=0], homeostatic model assessment of insulin resistance (HOMA-IR) (-0.57, 95% CI: -0.75 to -0.40 L, P<0.00001, I2=2%), serum total cholesterol (TC) (-6.87 mg/dL, 95% CI: -10.28 to -3.47 mg/dL, P<0.0001, I2=95%), serum triglyceride (-4.03 mg/dL, 95% CI: -5.53 to -2.52 mg/dL, P<0.00001, I2=97%), serum low-density lipoprotein cholesterol (LDL-C) (-6.64 mg/dL, 95% CI: -11.58 to -1.70 mg/dL, P=0.008, I2=99%), serum very low-density lipoprotein cholesterol (VLDL-C) (-3.29 mg/L, 95% CI: -6.54 to -0.05 mg/L, P=0.05, I2=72%), serum high-sensitivity C-reactive protein (hs-CRP) (-8.97mg/dL, 95% CI: -17.66 to -0.28 mg/dL, P=0.04, I2=99%), an improvement in serum high-density lipoprotein cholesterol (HDL-C) (2.94 mg/dL, 95% CI: 0.63 to 5.26 mg/dL, P=0.01, I2=87%), but no effect on serum glucose (-0.76 mg/dL, 95% CI: -1.71 to 0.19 mg/dL, P=0.12, I2=73%) was found. DISCUSSION The current meta-analysis demonstrated that omega-3 fatty acid supplementation for women with PCOS resulted in a statistical improvement in insulin, HOMA-IR, TC, triglyceride, LDL-C, VLDL-C, and HDL-C, but did not affect serum glucose. The limitation of this paper is due to the lack of included research literature.
Matrix-trapped viruses can prevent invasion of bacterial biofilms by colonizing cells

Bacteriophages can be trapped in the matrix of bacterial biofilms, such that the cells inside them are protected. It is not known whether these phages are still infectious and whether they pose a threat to newly arriving bacteria. Here, we address these questions using Escherichia coli and its lytic phage T7. Prior work has demonstrated that T7 phages are bound in the outermost curli polymer layers of the E. coli biofilm matrix. We show that these phages do remain viable and can kill colonizing cells that are T7-susceptible. If cells colonize a resident biofilm before phages do, we find that they can still be killed by phage exposure if it occurs soon thereafter. However, if colonizing cells are present on the biofilm long enough before phage exposure, they gain phage protection via envelopment within curli-producing clusters of the resident biofilm cells.
Cubosomes: Versatile Nanosized Formulation for Efficient Delivery of Therapeutics.

Cubosomes are bicontinuous cubic phase nanoparticles with a size range from 10-500 nm. They offer various advantages with some limitations at the production level, e.g., cubosomes have the feature to encapsulate a large amount of the drug due to its large internal area owing to cuboidal shape thus has a larger area but limited in large scale production due to its high viscosity which is associated with the problem in homogenization. This nanoparticulate formulation is compatible for administration by various routes like oral, transdermal, topical, buccal, etc. The drug release mechanism from cubosomes was reported to be dependent on the partition coefficient and diffusion process. Compared with liposomes, cubosomes show many differences in various aspects like shape, size, ingredients, and mode of action. The main ingredients for the preparation of cubosomes include lipids, stabilizer, aqueous phases, and therapeutic agents. Several methods have been reported for cubosomes, including the top-down method, the bottom-up method, and the adopted coarse method. For the optimization of cubosomes, the key factors to be considered, which will affect the cubosomes characteristics include; the concentration of lipid, temperature, and pH. At present, many research groups are exploring the potential of cubosomes as biosensors and nanocarriers. Based on the latest reports and research, this review illuminates the structure of the Cubosomes, mechanism of the drug release, different methods of preparation with factors affecting the cubosomes, application of cubosomes in different sectors, differences from the liposomes, and advantages.
Pulmonary Vascular Remodeling Is an Early Feature of Fatal and Nonfatal Asthma.

Increased bronchial vascularization in patients with asthma is a welldocumented feature of airway remodeling (1) that has been shown to correlate with airflow limitation, bronchial hyperresponsiveness, and disease severity (2, 3). It has been proposed that the increased bronchial vasculature may promote airway inflammation and remodeling in asthma through chronic inflammatory cell recruitment, pooling of inflammatorymediators, andabnormalcell growthandproliferation. It remainsunknownwhether both the bronchial andpulmonary vascular systems supplying the lung are remodeled and at what stage the vascular changes occur. The contribution of the current study is to quantitatively assess the structure and extracellularmatrix composition (elastin and collagen) of distal pulmonary arteries and veins from pediatric andadultpatientswithasthmacomparedwithhealthycontrol subjects.