Miracle-dz/UniFAR-FTUs huggingface dataset:
World Workshop on Oral Medicine VII: Targeting the oral microbiome Part 2: Current knowledge on malignant and potentially malignant oral disorders.

OBJECTIVE The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa? MATERIALS AND METHODS A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified. RESULTS Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies. CONCLUSIONS Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa.
Venous Leg Ulcers in the UK: The Local Burden of Illness and the Allocation of Resources

The precise UK prevalence of venous leg ulcers (VLU) is currently unclear. Prevalence data is essential in order to calculate the costs and, to measure the impact of any therapeutic intervention. A review of the literature was undertaken to assess the prevalence and costs of VLU in order to collate available data for baseline, or comparative purposes. Thereafter, information on compression bandaging products obtained from the QuintilesIMS database, prescribed for one large city was collected and calculations made to estimate known prevalence in that geographic locality. Results from the literature search showed the prevalence to vary from 0.1 to 1.1 in the studies identified. The prevalence of leg ulcers (LUs) in compression in the city reviewed was calculated to be 0.1 in 2015. There is a lack of reliable information on the prevalence and cost of LUs. The estimated prevalence reported is in keeping with those calculated by SIGN (2010) but less than those reported by Guest et al (2016). The annual cost of treating patients with LUs in the UK has recently been reported to be Â£1,938 million (Guest et al, 2016). Traditionally, regional clinical commissioning groups (CCGs) and local health authorities have not requested prevalence and outcome data on LUs and, therefore, there is a gap in understanding the extent of the problem. Consequently, the budgeting of services by CCGs is based more on estimates than on prevalence data. Without more accurate prevalence data it is impossible to truly understand the scale of the problem and develop a plan on how best to move forward with improving LU care.
Hostility, Sodium Consumption, and Cardiovascular Response to Interpersonal Stress

Objective Previous studies have reported poorer health behaviors in high vs. low hostile subjects. The role of stress in these observed differences has not been explored although interpersonal stress does increase cardiovascular response in high hostiles. Given evidence that stress may induce increased salt-intake, this study examined the role of hostility and interpersonal stress in increasing sodium consumption in addition to cardiovascular reactivity. Method Sixty-nine male undergraduates were categorized into high (HiHo) and low hostile (LoHo) groups based on Buss-Durkee Hostility Inventory scores. Subjects engaged in either a math task with harassment, math task without harassment, or a control/rest condition. Sodium intake was assessed posttask by having subjects ingest a sodium-free soup that was presented with a saltshaker without any comments. Cardiovascular measures were also recorded. Results HiHo subjects consumed more salt than LoHo subjects irrespective of experimental condition. HiHo subjects who were harassed also exhibited greater cardiac output, systolic blood pressure, and forearm blood flow than did HiHo nonharassed, HiHo control, or LoHo subjects. Conclusion HiHo subjects exhibited increased salt-intake, although evidence for stress-induced salt-intake was not obtained. Nonetheless, the combination of salt and stress may contribute to the cardiovascular hyperreactivity and risk for cardiovascular disease in hostile individuals.
Common reducing subspace model and network alternation analysis

Motivated by brain connectivity analysis and many other network data applications, we study the problem of estimating covariance and precision matrices and their differences across multiple populations. We propose a common reducing subspace model that leads to substantial dimension reduction and efficient parameter estimation. We explicitly quantify the efficiency gain through an asymptotic analysis. Our method is built upon and further extends a nascent technique, the envelope model, which adopts a generalized sparsity principle. This distinguishes our proposal from most xisting covariance and precision estimation methods that assume element‐wise sparsity. Moreover, unlike most existing solutions, our method can naturally handle both covariance and precision matrices in a unified way, and work with matrix‐valued data. We demonstrate the efficacy of our method through intensive simulations, and illustrate the method with an autism spectrum disorder data analysis.
Phenotypic Stability of Sex and Expression of Sex Identification Markers in the Adult Yesso Scallop Mizuhopecten yessoensis throughout the Reproductive Cycle

Simple Summary Bivalve sex is thought to fluctuate depending on environmental conditions. So far, there has been no investigation on the phenotypic stability of sex in the commercially important Yesso scallop Mizuhopecten yessoensis. The present study revealed that the sex of the Yesso scallop is stable after initial sex differentiation and that this species maintains a sex-stable maturation system throughout its life. In addition, gonad differentiation for each sex was precisely characterized by using molecular markers throughout the maturational cycle. Abstract The objective of the present study was to analyze the phenotypic stability of sex after sex differentiation in the Yesso scallop, which is a gonochoristic species that has been described as protandrous. So far, no study has investigated in detail the sexual fate of the scallop after completion of sex differentiation, although bivalve species often show annual sex change. In the present study, we performed a tracking experiment to analyze the phenotypic stability of sex in scallops between one and two years of age. We also conducted molecular marker analyses to describe sex differentiation and gonad development. The results of the tracking experiment revealed that all scallops maintained their initial sex phenotype, as identified in the last reproductive period. Using molecular analyses, we characterized my-dmrt2 and my-foxl2 as sex identification markers for the testis and ovary, respectively. We conclude by proposing that the Yesso scallop is a sex-stable bivalve after its initial sex differentiation and that it maintains a sex-stable maturation system throughout its life. The sex-specific molecular markers identified in this study are useful tools to assess the reproductive status of the Yesso scallop.
ASSOCIATION OF TNF- α-308G>A POLYMORPHISM WITH SUSCEPTIBILITY TO CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND There is increasing evidence to show that TNF-α -308G>A polymorphism may be a risk factor for celiac disease, but the results are inconsistent. OBJECTIVE Thus, we aimed to perform a meta-analysis involving published studies up to January 2019 to elucidate the association. METHODS To assess the effect of TNF-α -308G>A polymorphism on celiac disease susceptibility, we searched PubMed, ISI Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI) databases to identify eligible studies, without restriction. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to celiac disease. RESULTS A total of 11 studies with 1147 cases and 1774 controls were selected for this meta-analysis. The pooled results indicated that TNF-α -308G>A polymorphism was associated with increased risk of celiac disease (A vs G: OR=2.077, 95% CI=1.468-2.939, P=≤0.001; AA vs GG: OR=8.512, 95% CI=3.740-19.373, P=≤0.001; AA+AG vs GG: OR=1.869, 95% CI=1.161-3.008, P=0.010; and AA+AG vs GG: OR=4.773, 95% CI=3.181-7.162, P≤0.001). Subgroup analysis by ethnicity also revealed significant association in Caucasians. In addition, there was a significant association between TNF-α -308G>A polymorphism and celiac disease risk in Italy, Spain and PCR-FRLP group studies. CONCLUSION Our meta-analysis suggests that the TNF-α -308G>A polymorphism plays an important role in celiac disease susceptibility. However, our results are still needed to strengthen by further studies in different ethnicities and larger sample sizes.
Isotopic synovectomy with P‐32 in paediatric patients with haemophilia

Isotopic synovectomy is being proposed as an option in the treatment of patients with haemophilic arthropathy. We present our experience with 11 paediatric patients who underwent 17, P‐32 isotopic synovectomies for chronic haemophilic arthropathy. P‐32 was injected into the joint per protocol, approved by the institutional review board. All our patients were male. Nine were factor VIII and two were factor IX deficient. The following joints were treated: ankle (n=10 procedures), elbow (n=5) and knee (n=2). The first procedure was performed on December 1993. None were human immunodeficiency virus positive. Mean age at the first procedure was 10.8 years (range, 5.2–15.2 years). Mean pretreatment joint clinical scores using the World Federation of Hemophilia guidelines for the ankle was 5.5 (SD ± 2.3), the elbow 4.2 (±2.5), and knee 5.5 (±3.5); the corresponding post‐treatment scores were 2.6 (±2.0), 1.4 (±0.5) and 2.5 (±3.5) respectively. Presynovectomy mean radiological scores using the Pettersson method were: ankle 1.8, elbow 1.8, and knee 1.5. A scoring system used in our centre for evaluating joints using magnetic resonance imaging (MRI) gave the following mean pretreatment scores: ankle 9.5, elbow 8.4, and knee 5.0. A marked decrease (an 80–100% decrease) in bleeding was seen in 13 of 17 procedures, and a moderate decrease (51–79% decrease) in two procedures, accounting for 85% reduction in bleeding into the target joints. The procedure was well tolerated and no untoward side‐effects were noted as of May 1999, with a median follow‐up of 40 months (range 19–65 months). None had any clinical evidence of cancer. Three patients had their joints retreated [elbow (one), ankle (two)]. These procedures were also well tolerated. In conclusion, in our study, isotopic synovectomy using P‐32 appears to be feasible, safe and efficacious in the treatment of haemophilic arthropathy in paediatric patients who have been followed for a median of 40 months. As previously shown, MRI appears to give more detailed information about joint arthropathy than plain radiographs.
Combination Therapy for Treating Advanced Drug-Resistant Acute Lymphoblastic Leukemia

Blocking BAFF-R early in ALL promotes killing of leukemic cells. However, if given at later disease stages, efficacy is limited due to TGFβ. Combining VAY736 and a TGFβR1 inhibitor improved treatment efficacy in advanced and drug-resistant ALL. Drug-resistant acute lymphoblastic leukemia (ALL) patients do not respond to standard chemotherapy, and an urgent need exists to develop new treatment strategies. Our study exploited the presence of B-cell activating factor receptor (BAFF-R) on the surface of drug-resistant B-ALL cells as a therapeutic target. We used anti–BAFF-R (VAY736), optimized for natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity (ADCC), to kill drug-resistant ALL cells. VAY736 antibody and NK cell treatments significantly decreased ALL disease burden and provided survival benefit in vivo. However, if the disease was advanced, the ADCC efficacy of NK cells was inhibited by microenvironmental transforming growth factor-beta (TGFβ). Inhibiting TGFβ signaling in NK cells using the TGFβ receptor 1 (R1) inhibitor (EW-7197) significantly enhanced VAY736-induced NK cell–mediated ALL killing. Our results highlight the potential of using a combination of VAY736 antibody with EW-7197 to treat advance-stage, drug-resistant B-ALL patients.
Similar but different: virtual memory CD8 T cells as a memory‐like cell population

Immunological memory is a phenomenon where the immune system can respond more rapidly to pathogens and immunological challenges that it has previously encountered. It is defined by several key hallmarks. After an initial encounter, immune cells (1) expand and (2) differentiate to form memory cell populations. Memory cells are (3) long‐lived and (4) facilitate more rapid immune responses to subsequent infection because of (i) an increase in cell number, (ii) a decrease in the signaling threshold required for entry into cell cycle or effector function and (iii) localization of cells to tissue sites for surveillance. Classically, immunological memory has been antigen specific but it is becoming apparent that mechanisms of immunological memory can be co‐opted by innate or antigen‐inexperienced immune cells to generate heterogeneity in immune responses. One such cell is the virtual memory CD8 T (TVM) cell, which is a semi‐differentiated but antigen‐naïve CD8 T‐cell population. This review will summarize current knowledge of how TVM cells are generated, their memory‐like hallmarks, how they are maintained during steady state, infection and aging, and propose a model to integrate key signaling pathways during their generation.
Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma

Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regarding their PD-1, PD-L1, and CTLA-4 expression by immunohistochemistry (IHC). The prognostic values for cancer-specific survival (CSS) and overall survival (OS) were analyzed for those not exposed to CI therapy. The expression of PD-1 in tumor-infiltrating mononuclear cells (TIMC) and PD-L1 in tumor cells was detected in 9.4% and 12.3%, respectively (Immune reactive score (IRS) > 0). Furthermore, PD-L1 expression in TIMC (IRS > 0) and CTLA-4 expression in TIMC (>1% positive cells) was detected in 4.8% and 6.3%. PD-1 expression and CTLA-4 expression were significantly associated with a worse OS and CSS in log rank survival analysis and univariate Cox regression analysis. CTLA-4 expression is a prognostic marker that is independently associated with a worse outcome in multivariate Cox regression analysis in the whole cohort (OS: p = 0.013; CSS: p = 0.048) as well as in a non-metastatic subgroup analysis (OS: p = 0.028; CSS: p = 0.022). Patients with combined CTLA-4 expression and PD-1-expression are at highest risk in OS and CSS. In RCC patients, PD-1 expression in TIMC and CTLA-4 expression in TIMC are associated with a worse OS and CSS. The combination of PD-1 expression in TIMC and CTLA-4 expression in TIMC might identify high risk patients. This is, to our knowledge, the first description of CTLA-4 expression to be a prognostic marker in RCC.
Low intake of vitamins B6, C, E and folate from dietary sources may lead to a higher risk of developing frailty in older adults

Commentary on: Balboa-Castillo R, Struijk EA, Lopez-Garcia E et al . Low vitamin intake is associated with risk of frailty in older adults. Age and Ageing 2018;47(6):872–879. There is growing evidence that inadequate nutrition is a determining factor in the development of frailty among older adults, both in terms of the quantity of calories consumed and the quality of nutrients taken.1 Frailty leads to reduced quality of life, loss of function and independence, and increased morbidity and mortality. …
Childhood circumstances, psychosocial factors and the social impact of adult oral health.

OBJECTIVES The aim of this study was to determine whether childhood familial conditions are associated with the social impact of adult oral health and to investigate the role of psychosocial attributes as potential mechanisms by which risk might be conveyed from childhood to adulthood. METHODS Using a cross-sectional design, self-report data were obtained from a representative sample of adults in Australia with a telephonic interview and a self-completed questionnaire. The dependent variable was the sum of impacts on the short-form Oral Health Impact Profile (OHIP-14). Childhood familial conditions included socioeconomic position assessed by paternal occupation group, family structure and quality of rearing. Current adult sense of control, perceived stress and satisfaction with life were assessed with standard scales and social support was evaluated with four items. RESULTS Data were obtained for 3678 dentate adults aged 18-91 years. In bivariate analysis controlling for sex, age and household income in adulthood, parenting style was significantly associated with OHIP-14 scores (anova, P < 0.001). Adults who were reared supportively had more favourable scores on all four current psychosocial attributes (anova, P < 0.001). All four psychosocial attributes were associated with summed OHIP scores in the expected directions (anova, P < 0.001). In the multiple regression, parental rearing style was significantly associated with social impact after adjusting for sex, age and household income in adulthood, but was no longer significant in the presence of the psychosocial factors. CONCLUSION The importance of parental rearing to adult oral health may be mediated through the quality and nature of psychosocial attributes.
Dietary intake, physical activity and energy expenditure of Malaysian adolescents.

INTRODUCTION Paediatric obesity is a public health concern worldwide as it can track into adulthood and increase the risk of adult morbidity and mortality. While the aetiology of obesity is multi-factorial, the roles of diet and physical activity are controversial. Thus, the purpose of this study was to report on the differences in energy intake, diet composition, time spent doing physical activity and energy expenditure among underweight (UW), normal weight (NW) and at-risk of overweight (OW) Malaysian adolescents (317 females and 301 males) aged 11-15 years. METHODS This was a cross-sectional study with 6,555 adolescents measured for weights and heights for body mass index (BMI) categorisation. A total of 618 subjects were randomly selected from each BMI category according to gender. The subjects' dietary intake and physical activity were assessed using self-reported three-day food and activity records, respectively. Dietary intake components included total energy and macronutrient intakes. Energy expenditure was calculated as a sum of energy expended for basal metabolic rate and physical activity. Time spent (in minutes) in low, medium and high intensity activities was also calculated. RESULTS The OW adolescents had the highest crude energy intake and energy expenditure. However, after adjusting for body weight, the OW subjects had the lowest energy intake and energy expenditure (p-value is less than 0.001). The study groups did not differ significantly in time spent for low, medium and high intensity activities. Macronutrient intakes differed significantly only among the girls where the OW group had the highest intakes compared to UW and NW groups (p-value is less than 0.05). All study groups had greater than 30 percent and less than 55 percent of energy intake from fat and carbohydrate, respectively. CONCLUSION The data suggested that a combination of low energy expenditure adjusted for body weight and high dietary fat intake may be associated with overweight and obesity among adolescents. To prevent overweight and obesity among children and adolescents, strategies that address eating behaviours and physical activity are required. Various segments of the society must be involved in efforts to promote healthful dietary intakes and active lifestyle in children and adolescents.
Cost–effectiveness analysis for multinational clinical trials

Clinical trials of cost–effectiveness are often conducted in more than one country. The two most common ways of dealing with the multinational nature of the data are either to calculate a pooled estimate or to stratify results by country. Since the between‐country heterogeneity in costs is potentially substantial, pooled estimates may be difficult to interpret for any one country. Policy decisions are often made at a national level, and so country‐specific results are important. However, country‐specific analyses will be based on fewer patients and will often fail to provide adequate precision for statistical analyses.
Carbon Dots-Decorated Bi2WO6 in an Inverse Opal Film as a Photoanode for Photoelectrochemical Solar Energy Conversion under Visible-Light Irradiation

This work focuses on the crystal size dependence of photoactive materials and light absorption enhancement of the addition of carbon dots (CDs). mac-FTO (macroporous fluorine-doped tin oxide) films with an inverse opal structure are exploited to supply enhanced load sites and to induce morphology control for the embedded photoactive materials. The Bi2WO6@mac-FTO photoelectrode is prepared directly inside a mac-FTO film using a simple in situ synthesis method, and the application of CDs to the Bi2WO6@mac-FTO is achieved through an impregnation assembly for the manipulation of light absorption. The surface morphology, chemical composition, light absorption characteristics and photocurrent density of the photoelectrode are analyzed in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV–vis diffuse reflectance spectra (DRS), Energy dispersive X-ray analysis (EDX) and linear sweep voltammetry (LSV).