Miracle-dz/UniFAR-FTUs huggingface dataset:
Species and genetic diversity are not congruent in fragmented dry grasslands

Abstract Biological diversity comprises both species diversity (SD) and genetic diversity (GD), and it has been postulated that both levels of diversity depend on similar mechanisms. Species‐genetic diversity correlations (SGDC) are therefore supposed to be generally positive. However, in contrast to theory, empirical data are contradictory. Furthermore, there is a pronounced lack of multispecies studies including also the ecological factors potentially driving species and genetic diversity. We analyzed the relationship between the species diversity of dry grasslands and the genetic diversity of several dry grassland plant species, therefore, in the context of habitat fragmentation and habitat conditions. Our study revealed a lack of correlation between species and genetic diversity. We demonstrated previously that SD mainly depends on habitat conditions (vegetation height and cover of litter), whereas GD is significantly affected by habitat fragmentation (distance to the nearest dry grassland in 1830 and connectivity in 2013). This seems to be the main reason why SD and GD are not congruent in fragmented grasslands. Our results support, hence, the observation that positive SGDCs can mainly be found in natural, island‐like study systems in equilibrium and at similar levels of heterogeneity. In fragmented dry grassland ecosystems, which differ in heterogeneity, this state of equilibrium may not have been reached mitigating the positive relationship between SD and GD. From our study, it can be concluded that in fragmented dry grasslands, the protection of SD does not necessarily ensure the conservation of GD.
Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on the ovarian cancer proliferation, formation and maintenance of the disseminated ovarian cancer cells. Roles of Notch and FSH in the ovarian cancer pathogenesis was investigated using ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in the ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. The spheroids from the ascites of the patients, as well as, the spheroids from the ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNAs and secreted the hormone into the medium. In contrast, the primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. The ovarian cancer cell spheroids also exhibited higher expression of the FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Further, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.
The Costs of Confronting Osteoporosis: Cost Study of an Australian Fracture Liaison Service

Fracture liaison services (FLS) are an accepted approach to lowering rates of osteoporotic refractures. However, resource allocations to FLS are open to challenge, as most relevant cost analyses are based on anticipated, rather than observed, benefits. To support informed decision making, we have estimated the cost of operating an FLS, from the perspective of the Australian health system, with real life costs. On the basis of hospital records, we compared total costs of two cohorts of patients presenting with minimal trauma fractures (MTFs) at two hospital emergency departments (EDs) across a 6‐month period (July to December 2010). The treatment cohort (FLS Cohort, n = 515) attended an ED at a hospital offering FLS post‐fracture care; the Usual Care Cohort (n = 416) attended an ED at a hospital without an FLS. Hospital records were reviewed for further attendance of both groups at their respective hospitals’ EDs with refractures for the subsequent 3 years. Costs were constructed from “bottom up” with a “microcosting” approach. Total costs for both cohorts included any FLS and the costs of refractures. Cohort costs were estimated for every 1000 patients over the 3 observed years. Compared with the Usual Care Cohort, the FLS Cohort had 62 fewer fractures per 1000 patients and $617,275 lower costs over 3 years. In a sensitivity analysis, where 20% of the Usual Care Cohort received FLS preventative treatment, FLS Cohort costs were lower by $880,154. As both hospitals consistently process around 2000 patients per year, the estimated annual saving is $1.2 million to $1.8 million (Australian dollars). From the perspective of the Australian public health system, investment in FLS can be a financially effective way of reducing the cost of osteoporotic fracture management. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Early diagnosis of cardiac involvement in systemic lupus erythematosus via global longitudinal strain (GLS) by speckle tracking echocardiography

Introduction: Systemic lupus erythematosus (SLE) myocarditis occurs in between 5% and 10% of patients with lupus. Global longitudinal strain (GLS) via speckle tracking echocardiography can detect cardiac involvement in patients suffering from SLE. We decided to determine the echocardiographic features and subsequent early diagnosis of cardiac involvement in patients with SLE utilizing the GLS index via speckle tracking echocardiography. Methods: In this cross-sectional study, we compared female patients with SLE of at least 2 years’ duration and healthy controls in terms of the left ventricular (LV) GLS via speckle tracking echocardiography. After data collection in both groups, the GLS index and the ejection fraction were evaluated. Results: We analyzed and compared the LV echocardiographic parameters of 33 patients with SLE (mean age=25.45±0.63 years) with those of 35 healthy controls (mean age=27±0.45 years). The apical 2-chamber view indicated a significant decrease in the LV GLS in the case group by comparison with the healthy controls (P=0.005). The LV GLS in the apical 3-chamber view was significantly lower in the case group than in the control group (P=0.006). The LV GLS in the apical 4-chamber view revealed no significant difference between the case and healthy control groups (P=0.2). While there was a significant difference between the case and control groups visà- vis the LV GLS (P=0.02), the LV ejection fraction measured with the Simpson method showed no significant difference between the 2 groups (P=0.96). Conclusion: GLS speckle tracking echocardiography is a noninvasive method with diagnostic and prognostic values; it may, therefore, be a sensitive marker for the diagnosis of myocarditis and other cardiac involvements in patients with SLE.
Resistance rates of non-albicans Candida infections in Taiwan after the revision of 2012 Clinical and Laboratory Standards Institute breakpoints

Purpose In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised its breakpoints for drugs and species because of the increase in non-albicans Candida infections and their drug resistance. Following global trends, the non-albicans candidemia resistance rate has increased in Taiwan as well. To update the antifungal susceptibility of non-albicans candidemia isolates, we conducted a multicenter study using the revised break points. Patients and methods Patients with non-albicans candidemia infections were identified at five tertiary hospitals in Taiwan from July 1, 2011, to June 30, 2014. The broth microdilution method using a Sensititre YeastOne system was performed for the determination of minimum inhibitory concentration (MIC). The susceptibility was interpreted based on the guidelines of the CLSI (CLSI M27-S4 and M27-S3). Results Candida tropicalis was the predominant non-albicans candidemia pathogen (42.4%), and it showed increased fluconazole non-susceptibility (36.3%) when compared to the results from previous studies. In particular, C. tropicalis showed high cross-resistance to azole agents. C. tropicalis isolates that were found to be resistant to fluconazole also showed increased resistance to voriconazole (82.2%) and posaconazole (100%). The increased non-susceptibility of Candida glabrata to multiple antifungal agents, based on the revised break points, resulted from an increase in dose-dependent susceptibility (94.4%) rather than from an increase in resistance (5.6%). Conclusion The resistance rate of non-albicans candidemia isolates is increasing, particularly for C. tropicalis and C. glabrata.
Comparing Serum and Salivary Levels of Vitamin D in Patients with Recurrent Aphthous Stomatitis and Healthy Individuals

Statement of the Problem: Recurrent aphthous stomatitis (RAS) is the most prevalent ulcerative condition of the oral mucosa. Many studies have emphasized on immunologic factors as the reason of inducing RAS; however, the exact etiologic cause of RAS has not been identified yet. Vitamin D has an endocrine function and regulatory effects on the immune system. It has potential therapeutic effects on autoimmune diseases, psoriasis, and neoplasms. Vitamin D deficiency has been detected in some autoimmune diseases such as rheumatoid arteritis. Purpose: The aim of the present study was to compare the serum and salivary levels of vitamin D in patients with RAS and healthy individuals. Materials and Method: In this cross sectional study, patients with RAS, referring to the Department of Oral Medicine, Tabriz Faculty of Dentistry, were evaluated after taking medical history, clinical examinations, and completing an informed consent form. The serum and salivary vitamin D levels were compared between case (n=26) and control (n=26) groups. Results: The mean serum vitamin D levels in the case and control groups were 33.0. 7±12.41 and 50.89±9.30 (ng/dL), respectively, with a statistically significant difference (p<0.001). On the other hand, the mean salivary vitamin D levels in the case and control groups were 17.36± 8.01 and 20.79±6.31 (ng/dL), respectively, with no statistically significant difference (p= 0.09). In addition, the correlation between the serum and salivary levels of vitamin D was 56%, being statistically significant (p< 0.001). Conclusion: The serum levels of vitamin D in patients with RAS were significantly less than that in healthy individuals; however, there were no significant differences in salivary vitamin D levels between patients with RAS and healthy individuals. In addition, there was a significant and positive correlation between serum and salivary levels of vitamin D in all patients.
Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder

Micropapillary carcinoma of the bladder (MPBC) is a variant type of infiltrating urothelial carcinoma, which portends a poor biological behavior in terms of disease stage at first diagnosis and clinical outcome; its peculiar morphology raises issues concerning the ability of tumor detection by imaging techniques and proper biopsy procedure, and the appropriate treatment for non-muscle infiltrating and muscle-infiltrating MPBC remains a matter of debate. On the basis of its established prognostic and therapeutic role in breast and gastro-esophageal cancer in the first instance, the human epidermal growth factor receptor-2 (HER2) has been investigated in selected case series of MPBC over the last 10 years. The aim of the present review was to summarize the existing evidence on HER2 status in MPBC, and to discuss its present and future utility in risk assessment and treatment choice of this uncommon, yet aggressive, disease.
Standing geographic variation in eclosion time and the genomics of host race formation in Rhagoletis pomonella fruit flies

Abstract Taxa harboring high levels of standing variation may be more likely to adapt to rapid environmental shifts and experience ecological speciation. Here, we characterize geographic and host‐related differentiation for 10,241 single nucleotide polymorphisms in Rhagoletis pomonella fruit flies to infer whether standing genetic variation in adult eclosion time in the ancestral hawthorn (Crataegus spp.)‐infesting host race, as opposed to new mutations, contributed substantially to its recent shift to earlier fruiting apple (Malus domestica). Allele frequency differences associated with early vs. late eclosion time within each host race were significantly related to geographic genetic variation and host race differentiation across four sites, arrayed from north to south along a 430‐km transect, where the host races co‐occur in sympatry in the Midwest United States. Host fruiting phenology is clinal, with both apple and hawthorn trees fruiting earlier in the North and later in the South. Thus, we expected alleles associated with earlier eclosion to be at higher frequencies in northern populations. This pattern was observed in the hawthorn race across all four populations; however, allele frequency patterns in the apple race were more complex. Despite the generally earlier eclosion timing of apple flies and corresponding apple fruiting phenology, alleles on chromosomes 2 and 3 associated with earlier emergence were paradoxically at lower frequency in the apple than hawthorn host race across all four sympatric sites. However, loci on chromosome 1 did show higher frequencies of early eclosion‐associated alleles in the apple than hawthorn host race at the two southern sites, potentially accounting for their earlier eclosion phenotype. Thus, although extensive clinal genetic variation in the ancestral hawthorn race exists and contributed to the host shift to apple, further study is needed to resolve details of how this standing variation was selected to generate earlier eclosing apple fly populations in the North.
Effects of coagulation factor VII polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and maintenance phases of warfarin therapy

Purpose This study aims to investigate the relationships between genetic polymorphisms of the coagulation factor VII (FVII) gene and warfarin responsiveness and sensitivity. Patients and methods The study population consisted of 417 subjects (207 Jordanian cardiovascular patients and 210 healthy individuals). Cardiovascular patients were classified into two groups: those sensitive to warfarin dosage (sensitive, moderate, and resistant) and those responsive to warfarin based on International Normalized Ratios (INRs; poor, good, and extensive responders). The HVR4 polymorphism of the FVII gene was genotyped. Results Our results showed that there are significant differences between patients and controls according to both genotypic and allelic frequencies (P<0.0001) in the genetic susceptibility study. Moreover, the pharmacogenetics study reported that HVR4 had no association with warfarin sensitivity or responsiveness during the initiation and maintenance phases of therapy, the only significant differences were in the INR outcome measured during the maintenance phase of therapy (P=0.012). Conclusion Our data suggests lacking of association between the HVR4 polymorphism in the FVII gene and warfarin sensitivity and responsiveness during the initiation and maintenance phases of therapy. It is possible that these patients carry additional mutations in genes involved in the coagulation pathway.
Alveolar blood clots and platelet-rich fibrin induce in vitro fibroblast proliferation and migration

Wound healing process comprises a complex network of cells and molecules that are regulated in order to pursue tissue regeneration. Our study focused on the capacity of alveolar blood clots (ABCs), platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) to induce in vitro fibroblasts proliferation and migration as a measure of alveolar regeneration. Using cellular impedance with xCELLigence technology we quantified the proliferation and the migration capacity of L929 fibroblast standard cell line in the presence of 4 different ABCs and 3 different PRFs harvested from healthy individuals during standard tooth extraction. We obtained a clear cellular proliferation induced by the compounds mainly after 24 h of cultivation, in a dose-dependent manner. After 48 h of cultivation we registered activated proliferation, but slightly decreased compared to the 24 h profile. Our data confirm that the presence of the blood clot is involved in the regenerative processes. The migratory capacity of fibroblasts was statistically activated by the PL compounds while not affected by the tested PRFs. The chemical mediators present within the blood clot, either produced by inflammatory cells captive within, or by endothelial or mesenchymal cells induced fibroblastic proliferation and subsequent collagen deposition.
Distribution and Characterization of Monilinia spp. Causing Apple Fruit Decay in Serbia.

Brown rot, caused by Monilinia spp. , is an economically important pre- and postharvest disease of pome and stone fruits worldwide. In Serbia, apple is the most widely grown pome fruit, and the distribution of economically important Monilinia spp. responsible for apple brown rot is unknown. Hence, we conducted a three year survey, from 2010 to 2012, where 349 isolates were obtained from six orchards and four storage facilities from five different apple cultivars with brown rot symptoms. Morphological characterization of the isolates, multiplex PCR, and phylogenetic analysis revealed four species: M. fructigena, M. laxa, M. fructicola, and Monilia polystroma. All species were found in the orchard and in storage, with M. fructigena predominating, followed by M. polystroma. Representative isolates were analyzed in vitro and in vivo where differences in growth rate, sporulation, and virulence on apple fruit were observed. Findings from this investigation demonstrate diversity in the species responsible for pre- and postharvest apple brown rot, which has significant implications for pathogen detection and for developing disease-specific management strategies.
Adaptive NK cell reconstitution is associated with better clinical outcomes.

BACKGROUND Human cytomegalovirus (CMV) reactivation is a common occurrence early after transplant and is associated with heterogeneous NK cell subset expansion. These adaptive NK cell expansions are highly variable between recipients, with respect to magnitude and relative frequencies of adaptive NK cell subsets. METHODS To gain insight into the factors that influence adaptive NK cell expansion from a CMV naive graft source, we performed a high-resolution NK cell and CD8+ T cell phenotypic analysis of 215 patients with hematological malignancies that were transplanted with 2 partially HLA matched CMV negative umbilical cord blood units. RESULTS We found that adaptive NK cells were significantly higher in recipients who received nonmyeloablative conditioning (NMAC) relative to myeloablative conditioning (MAC), and high CMV neutralizing antibody titers correlated with the degree of adaptive NK cell expansion. The frequencies of adaptive NK cell subsets (defined by NKG2C, FcεRγ, EAT-2, and SYK expression) that reconstitute from donor hematopoietic progenitor cells largely matched the frequencies observed in the NK cell compartment of the recipient prior to conditioning, suggesting that host - as well as viral reactivation factors - may determine the phenotypic diversification after transplant. Additionally, multivariable analyses show that higher adaptive NK cell expansion associated with better disease-free survival. CONCLUSIONS Our findings provide important insights into adaptive NK cell reconstitution after transplant and support a role for adaptive NK cells in promoting better clinical outcomes. FUNDING The NIH and the National Marrow Donor Program.
Maternal witness to intimate partner violence during childhood and prenatal family functioning alter newborn cortisol reactivity

Abstract Witnessing intimate partner violence (IPV) during childhood is a risk factor for mental health problems across the lifespan. Less is known about the intergenerational consequences of witnessing IPV, and if the current family climate buffers intergenerational effects of witnessing violence. The mother’s experience of witnessing IPV against her own mother during childhood, prenatal family dysfunction, and prenatal perceived stress were examined as predictors of offspring cortisol in the first month of life (N = 218 mother–infant dyads). Mothers reported on witnessing IPV in their childhoods, prenatal family dysfunction, and prenatal perceived stress in pregnancy. At 2 days and again at 1 month postpartum, infants engaged in a neurobehavioral exam to assess infant cortisol reactivity. Infants whose mothers witnessed IPV in childhood exhibited alterations in their baseline cortisol and their cortisol reactivity at 1 month of age, whereas family dysfunction during pregnancy was associated with baseline cortisol and cortisol reactivity at 2 days of age. Prenatal perceived stress was not associated with infant cortisol at 2 days or 1 month. Prenatal family dysfunction and perceived stress did not moderate effects of the mother’s experience of witnessing IPV. Results support the view that maternal experiences in childhood and during pregnancy exert intergenerational effects on the HPA stress response system.