Miracle-dz/UniFAR-FTUs huggingface dataset:
Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis.

OBJECTIVE T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell-derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc. METHODS To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation. RESULTS High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients. CONCLUSION Dysregulated IL-13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target.
Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans

A potent, heat-labile leukotoxic material was extracted from Actinobacillus actinomycetemcomitans (strain Y4), an anaerobic gram-negative microorganism originally isolated from subgingival plaque in a patient with juvenile periodontitis. The cytopathic effects of Y4 toxin on purified monocytes were studied by the extracellular release of radioactive cytoplasmic markers and cell enzymes and by time-lapse microcinematography. Y4 toxin rapidly bound to the cells, producing dose- and time-dependent alterations culminating in cell death and release of intracellular constituents into the culture medium. The evidence to be presented suggests that the cell membrane of the monocyte may be the primary target in the development of these phenomena. Previous studies have shown that Y4 toxin also kills human polymorphonuclear leukocytes but not other cell types. It is conceivable that disruption of polymorphonuclear leukocytes and monocytes by Y4 toxin in the gingival crevice area may be relevant in the pathogenesis of juvenile periodontitis.
Risk factors associated with high bulk milk antibody levels to common pathogens in UK dairies

Infectious diseases pose a severe economic burden on the UK dairy industry. This study used bulk milk antibody levels in 1088 UK dairy herds to estimate the current UK prevalence of bovine viral diarrhoea virus (BVDV), bovine herpes virus 1 (BHV-1) and Leptospira hardjo. Questionnaires collected under the DairyCheck scheme (MSD Animal Health) were used concurrently to gather information on farm demographics and management practices. The prevalence of active BVDV infection was 58.6 per cent, of historic BVDV exposure was 88.6 per cent, of BHV-1 infection was 69.2 per cent and of L hardjo was 71.9 per cent. An increasing herd size and the purchasing of replacement cattle were risk factors for the presence of all three agents. Year-round calving was associated with a 1.9 times increased risk for having BVDV (P<0.005). The presence of a bull was associated with a 1.5 times increased risk for having BHV-1 (P<0.005). When compared with previous results, this study indicates a slight fall in the prevalence of BVDV within the UK dairy herd; however, BHV-1 and L hardjo levels appear to have remained constant. This study shows that herds purchasing cattle are at greater risk of infectious agents being present and therefore, if possible, a closed herd system should be implemented.
Positive Versus Negative Modulation of Different Endogenous Chemokines for CC-chemokine Receptor 1 by Small Molecule Agonists through Allosteric Versus Orthosteric Binding*

7 transmembrane-spanning (7TM) chemokine receptors having multiple endogenous ligands offer special opportunities to understand the molecular basis for allosteric mechanisms. Thus, CC-chemokine receptor 1 (CCR1) binds CC-chemokine 3 and 5 (CCL3 and CCL5) with Kd values of 7.3 and 0.16 nm, respectively, as determined in homologous competition binding assays. However, CCL5 appears to have a >10,000-fold lower affinity in competition against 125I-CCL3. Mutational mapping revealed that CCL3 and CCL5 both are strongly affected by systematic truncations of the N-terminal extension, whereas only CCL5 and not CCL3 activation is affected by substitutions in the main ligand binding pocket including the conserved GluVII:06 anchor point. A series of metal ion chelator complexes were found to act as full agonists on CCR1 and to be critically affected by the same substitutions in the main ligand binding pocket as CCL5 but not by mutations in the extracellular domain. In agreement with the overlapping binding sites, the small non-peptide agonists displaced radiolabeled CCL5 with high affinity. Interestingly, the same compounds acted as allosteric enhancers of the binding of CCL3, with which they did not overlap in binding site, leading to an increased Bmax and affinity of this chemokine mainly due to an increased association rate. It is concluded that a small molecule agonist through binding deep in the main ligand binding pocket can act as an allosteric enhancer for one endogenous chemokine and at the same time as a competitive blocker of the binding of another endogenous chemokine.
Profitability of Momentum Strategies in Malaysia

This paper examines the profitability of momentum strategies within the Malaysian stock market. Its also investigates relationship between stock returns and past trading volume. The study finds weak but insignificant evidence of momentum returns for Malaysian equities which is pervasive across different combinations of formation and holding periods with a maximum average return of 1.76 % per quarter. A clear reversal pattern with greater volatility is observed when non-overlapping portfolios are used. The study also finds that momentum return is more pronounced among stocks with low trading volume which contradicts previous studies. The impact of Asian financial crisis on momentum return is marginal and trend in the stock returns remains relatively unchanged.
Novel predictors of women's surname retention at marriage

Women’s marital surname change was investigated as a potential marital commitment signal, and strategy for enhancing investment from in-laws and husband. Hyphenating or keeping premarital surname for all U.S. destination brides marrying in Hawai'i in 2010 was significantly correlated with a women’s income measure (r = .78, p < .000) and with the analogous statistic for men (r = .64, p < .000), by bride’s state of residence. The women’s measure, only, remained significant under regression of both predictors. The interaction of state Gini and the women’s income measure in a regression including the interaction components as predictors was positively predictive (adjusted-R 2 = .57). None of several other predictors suggested by previous research or related to Gini or income were significant under regression, alongside the women’s income measure. The older the bride, from any jurisdiction, marrying in Hawai'i in 2010, the more likely to hyphenate/keep premarital surname (χ 2 (1) for linear trend = 1754.65, p < . 000). Among all opposite-sex couples (N = 167 couples) divorcing in a Canadian county in an 8-month period, 2013-2014, marriages the women in which underwent marital surname change lasted 60% longer, controlling for wife’s age at the time of marriage. When the woman’s marital surname change/retention was used as a regression predictor of number of children of the marriage alongside marriage duration in years, only the latter was predictive. Brides-to-be from across especially western and central Canada (N = 184) were surveyed as to marital surname hyphenation/retention versus change (DV 1), and attitude towards such retention in general (DV 2). Among women engaged to men, the hypothesized predictors of income and number of future children desired were positively predictive of marital surname retention/hyphenation under univariate analysis. Under multiple regression analysis using these and other predictors from the literature also found to be predictive of this DV under univariate analysis, only some of these other predictors were predictive. An EFA factor score calculated from several attitude items concerning in-laws, conceptualizable as In-law avoidance motivation, was not predictive of general attitude toward or actual retention/hyphenation, contrary to prediction.
Air‐abrasive debridement with glycine powder versus manual debridement and chlorhexidine administration for the maintenance of peri‐implant health status: a six‐month randomized clinical trial

STUDY DESIGN This single-masked, randomized and six-month clinical intervention trial including two study groups was planned to evaluate the efficacy of maintenance treatment with glycine powder on the periodontal health of peri-implant tissues. METHODS A total of 46 patients with partial or total edentulism, carrying a total of 88 implants, were assigned either to an air abrasive with the glycine powder treatment group (AAD) or to a manual debridement and clorexidine administration treatment group (MDA). Clinical data were collected before treatment and at 3 and 6 months after the treatment. Plaque index (PI), bleeding index (BOP), probing depth (PD), clinical attachment level (CAL) and bleeding score (BS) were analysed. RESULTS After 3 months, AAD treatment statistically significantly improved BS (P < 0.05); at 6 months, AAD treatment statistically significantly improved indexes PD, PI, BOP and BS (P < 0.05). In addition, the AAD treatment proved to be more effective than MDA in maintaining the peri-implant health of PD at three and 6 months, and of PI at 6 months (P < 0.05). There were no significant changes of CAL in both groups, and all the indexes remained within the physiological levels. CONCLUSIONS Within the limits of the study, treatment with glycine seems appropriate in the maintenance of peri-implant health and more effective than the traditional treatment with plastic curette and chlorhexidine.
The dental safety net, its workforce, and policy recommendations for its enhancement.

OBJECTIVE The dental safety net includes the facilities, providers, and payment programs that support dental care for underserved populations including those individuals disadvantaged by a variety of social, economic, and health conditions. Its components-health centers, dental schools, clinics, Medicaid-oriented dental practices, free-care programs, hospital emergency rooms, and others-vary in availability, comprehensiveness, continuity, and quality. The objective of this overview is to identify options and opportunities for policy changes to enhance oral health professional workforce in the safety net. METHODS Characteristics of the dental safety net and its components are reviewed and compared. RESULTS Professionals who now staff the dental safety net are a small subset of US dental providers and few current trainees anticipate practicing in these programs. Therefore, the safety net will continue to confront workforce challenges. CONCLUSIONS Multifactorial policy alternatives to increase the availability of dental professionals who care of the underserved include proposed changes in dental education, licensure, scope of practice for allied dental personnel, and federal and state financing of public insurance. Also needed are local efforts to establish social norms and activities among private dentists that engage more private practitioners in care of the underserved.
Clinical Outcome After Pedicled Segmental Pectoralis Major Island Flaps for Head and Neck Reconstruction

The pectoralis major is reliable for reconstruction of large defects in the head and neck area. In 2001, we introduced a muscle-sparing technique with preservation of the clavicular part of the muscle. So far, we did not report on its reliability and clinical outcome at the receptor site.Fifty-four pedicled segmental pectoralis major island flaps were used in 53 patients, from 2001 through 2006. As outcome measures, we studied the overall rate of complications, the rate of major complications, and the final outcome at the receptor sites. We differentiated for the types of complications and assessed operation indication (primary vs. salvage procedure), site of reconstruction, previous radiotherapy, and completeness of tumor excision as possible risk factors for complications. We compared our findings to those of a meta-analysis of 16 other studies.Complications at the receptor site were observed after 21 of the 54 operations (0.39). Eleven of these cases (0.52) required repeated surgery that was successful in 8 cases (0.72). Conservative treatment was successful in 8 cases (0.80). Final outcome was successful in 49 of the 54 operations (0.91). Previous radiotherapy was a significant risk factor for persisting complications. Salvage procedures were a significant risk factor for developing clinical fistulas and the risk of partial flap loss was significantly correlated with nonhypopharyngeal reconstructions. Our results were comparable with those found in the meta-analysis.Our muscle-sparing technique proved to be reliable with clinical results comparable with conventional techniques in addition to function preservation at the donor site.
How do young adults with cancer perceive social support? A qualitative study

ABSTRACT The social support of adolescents and young adults (AYA) has been studied very little. 18 interviews were conducted and evaluated with content analysis (inter-rater reliability = 0.87). All of the young adult cancer patients interviewed reported having received social support from at least two people (family, friends, and/or partner). Forms of emotional and instrumental support were more often reported than informational support. 12 participants described having received nonhelpful support, especially in areas of dealing with their situation, limited social participation, and distancing of friends. The participants considered social exchanges with other young adult cancer patients an important source of social support. AYA cancer patient networking should be improved.
Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection

ABSTRACT In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B′ with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.
Colour statistics of natural and man‐made surfaces

The reflectance spectra of natural and man‐made surfaces are highly constrained. Statistical analyses have been conducted that confirm that the surface reflectance spectra form a set of band‐limited functions with a frequency limit of approximately 0.02 cycles/nm. The reflectance spectra can be represented by a linear‐model framework and are adequately described by 6‐12 basis functions. However, the spectral properties of surfaces are not so constrained as to allow the human visual system to recover the surface properties from cone excitations. Furthermore, trichromatic colour devices such as scanners and cameras can only capture illumination‐specific colour information.
Congenital insensitivity to pain with anhidrosis (CIPA): Novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency

Congenital insensitivity to pain with anhidrosis is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self‐mutilating behavior, and mental retardation. The human TRKA gene (NTRK1), located on chromosome 1q21‐q22 encodes the receptor tyrosine kinase for nerve growth factor. We reported that TRKA is the gene responsible for CIPA and we developed a comprehensive strategy to screen for TRKA mutations and polymorphisms, as based on the gene’s structure and organization. Here we report eight novel mutations detected as either a homozygous or heterozygous state in nine CIPA families from five countries. Mendelian inheritance of the mutations was confirmed in seven families for which samples from either parent were available. However, non‐mendelian inheritance seems likely for the family when only samples from the mother and siblings, (but not from the father) were available. A paternal uniparental disomy for chromosome 1 is likely to be the cause of reduction to homozygosity of the TRKA gene mutation in this family. Interestingly, a Hispanic patient from the USA has two autosomal genetic disorders, CIPA and pyruvate kinase deficiency, whose genetic loci are both mapped to a closely linked chromosomal region. A splice mutation and a missense mutation were detected in the TRKA and PKLR genes from the homozygous proband, respectively. Thus, concomitant occurrence of two disorders is ascribed to a combination of two separate mutant genes, not a contiguous gene syndrome. This finding suggests a mechanism responsible for two autosomal genetic disorders in one patient. All these data further support findings that TRKA defects can cause CIPA in various ethnic groups. This will aid in diagnosis and genetic counseling of this painless but severe genetic disorder. Hum Mutat 18:308–318, 2001. © 2001 Wiley‐Liss, Inc.
Interprofessional support of mental well-being in schools: A Bourdieuan perspective

There is increasing international concern about the mental health and well-being of school-aged children, and the school is often seen as the optimum setting to deliver interagency interventions. This paper draws on a Scottish study examining the responses of local authorities, schools and other agencies to challenging behaviour related to poor mental health. It explores the ways in which the presence of workers from other agencies had an impact on the capacity of schools to respond to such issues. In Bourdieuan terms, the study showed that non-teaching workers imported into school developed new forms of ‘habitus’ leading to effective team work to support vulnerable pupils, but that they often operated in isolation from the wider teaching staff. Different professional cultures created significant barriers, which could be exacerbated by active resistance to meaningful engagement. Consequently, parallel working evolved, where staff from agencies other than education supported pupils experiencing difficulties, but there was little evidence of corresponding changes to ethos or pedagogy to meet the needs of pupils in school. Expertise pertaining to the mental well-being of pupils thus tended to be compartmentalized and was not readily transferred elsewhere, and this led to a disjointed experience for pupils. Our evidence strongly suggested that teachers preferred to learn from other teachers. This served to reinforce existing habitus and to isolate them from new ways of thinking. Potential ways of effecting culture change are suggested, through innovative training and development, linked to accountability, to challenge the new mode of parallel working before it becomes the status quo.
A Generative Model for Income and Capital Inequality

The purpose of this study is to formalize a generative model for income and capital inequality by focusing on the accumulation process of human and network capital. Using this model, we attempt to provide theoretical explanations to three empirical questions. First, why is the relationship between economic growth and income inequality expressed as an inverted U-curve? Second, why does societal relative deprivation increase when economic growth rises (the so-called China puzzle)? Third, why is income inequality stable despite the reduction of human capital inequality? The model assumes that people in a society experience repeatedly random chances of gaining capital interest with a success probability p . People gain additional capital as an interest when they succeed and incur a cost when they fail randomly. We show that the capital distribution approaches a lognormal distribution, and as an output of Cobb–Douglas production function, income distribution is also subject to a lognormal distribution. Analyzing the Gini coefficient and the average income as a function of parameters of the model, we derive the following implications. 1) The inverted U-curve is realized by the expansion of success chance. 2) The China puzzle occurs because the increase of average income and Gini coefficient are simultaneously followed by the expansion of success probability p under the range p ∈ (0,0.5). 3) The income inequality is stable, though human capital inequality decreases because of human and network capital elasticity and network capital diminishes the impact of human capital equalization on income inequality. In Section 4, we conclude the study and outline areas for further studies.