Miracle-dz/UniFAR-FTUs huggingface dataset:
The microbiome in PTEN hamartoma tumor syndrome

Germline PTEN mutations defining PTEN hamartoma tumor syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer history (P = 0.03, R 2 = 0.04). Fecal samples from PHTS cancer patients had relatively more abundant operational taxonomic units (OTUs) from family Rikenellaceae and unclassified members of Clostridia compared to those from non-cancer patients, whereas families Peptostreptococcaceae, Enterobacteriaceae, and Bifidobacteriaceae represented relatively more abundant OTUs among fecal samples from PHTS non-cancer patients. Functional metagenomic prediction revealed enrichment of the folate biosynthesis, genetic information processing and cell growth and death pathways among fecal samples from PHTS cancer patients compared to non-cancer patients. We found no major shifts in overall diversity and no clustering by cancer history among oral wash or urine samples. Our observations suggest the utility of an expanded study to interrogate gut dysbiosis as a potential cancer risk modifier in PHTS patients.
Glypicans: proteoglycans with a surprise.

The fact that membrane-bound heparan sulfate proteoglycans (HSPGs) regulate the activity of heparin-binding growth factor has been known for many years, but only during the last decade has the existence of two major families of membrane-bound HSPGs been established. One of these families, the glypicans, plays a critical a role in developmental morphogenesis. The interest in the study of glypicans has increased in the last few years as a result of the discovery that glypican-3 (GPC3) is mutated in an overgrowth and dysmorphic syndrome. The finding that GPC3 regulates body size was particularly surprising and suggested that this glypican may interact with signaling pathways that have not been traditionally associated with membrane-bound HSPGs. Here we will describe our current knowledge on the structure and function of glypicans. The involvement of these molecules in human pathologies will be discussed, including the different hypotheses with regard to the molecular basis of glypican function.
Is the accuracy of preoperative MRI stage in rectal adenocarcinoma influenced by tumour height?

Abstract Aim: To our knowledge, no prior studies have addressed the possible effects of tumour height on the accuracy of preoperative magnetic resonance imaging (MRI)-based staging relative to postoperative histopathological assessments in patients with adenocarcinoma of the rectum (RC). This study aimed to investigate whether the accuracy of preoperative MRI stage in RC is influenced by tumour height. Methods: A total of 489 consecutive RC patients scheduled for curative treatment between 2009 and 2013 were included. Of the 489 patients, 133 patients had preoperative chemoradiotherapy (CRT), and 356 patients underwent primary surgery. Low, mid and high RC were defined as a tumour <5 cm, 5–10 cm and >10 cm from the anal verge, respectively. Diagnostic MRI and, for patients with CRT, re-staging MRI features including tumour T-stage (mrT), distance between the tumour border and the distance to the mesorectal fascia (mrMRF), extramural tumour depth (mrEMD), extramural vascular invasion (mrEMVI) and nodal involvement (mrN) were correlated with the corresponding postoperative histopathological findings. Results: There were 115, 186 and 188 patients with low RC, mid RC and high RC, respectively. For all patients, the correlations between mrT and pT and between mrMRF and pCRM were not influenced by tumour height. None of the correlations between mrEMD, mrEMVI and mrN and the corresponding postoperative histopathological findings significantly differed for tumours of different heights. For patients with CRT, a remarkable proportion with low RC were overstaged as ymrT3 compared to ypT0-2. Conclusions: The ability to preoperatively use MRI to accurately stage is not influenced by tumour height. For patients with preoperative CRT, low RC may be MRI overstaged due to post-radiation fibrosis. We found that mrEMD predicts pEMD reliably and should therefore be considered in treatment decisions. Although new MRI techniques are emerging, preoperative RC staging remains incompletely definitive in daily clinical practice.
Objective tubal tinnitus: a report of two cases

Two patients with objective tinnitus due to continuous tubal opening are presented. The objective tubal tinnitus was found to be due to clonic spasm of the muscles of the pharynx and eustachian tube and it can be easily differentiated by means of sonotubometry alone. The acoustic events occurring during the clicking sound were analyzed and were similar to the swallowing sound. Movements of the tympanic membrane were not seen in any of these ears. However, the close relationship of the tensor tympani and tensor palati muscles could explain the movement of the tympanic membrane in some cases. I believe that stapedius muscle spasm or a patulous tube as such does not cause the clicking sound, but it can occur in association with palatal myoclonus. The objective tubal tinnitus is heard as a result of the walls of the eustachian tube snapping together. Transection of the tensor veli palatini muscle tendon may be a useful method of treatment if the patient experiences objective tinnitus which is very distressing.
Effect of food on the pharmacokinetics of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet in healthy volunteers

ABSTRACT Objective: Vildagliptin is an orally active, potent and selective DPP-4 inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha- and beta-cell responsiveness to glucose. Research design and methods: This open-label, single-center, randomized, two-period crossover study in healthy subjects (n = 23) ages 18–45 years investigated the effect of food on the pharmacokinetics of vildagliptin and metformin following administration of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet. Results: Administration of the fixed-dose combination tablet following a high-fat meal had no effect on vildagliptin AUC0–∞ (ratio of geometric mean for fed:fasted state, 1.10 [90 % CI 1.03, 1.18]), Cmax (ratio of means 0.98 [90 % CI 0.85, 1.13]) or median tmax (2.5 h in fed and fasted states). The rate of absorption of metformin was decreased when given with food, as reflected by the prolonged tmax (2–4 h) and reduction in Cmax (by 26 % ), but the extent of absorption was not changed. The food effect on the metformin component of the fixed-dose combination tablets was consistent with, but of a lesser magnitude compared with data stated. Conclusions: The vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet can be administered in the same manner as metformin, and can be recommended to be taken with meals to reduce the gastrointestinal symptoms associated with metformin.
Enoxaparin Treatment for Vulvodynia: A Randomized Controlled Trial

OBJECTIVE: To estimate the effectiveness of enoxaparin—a low-molecular-weight heparin with antiheparanase properties—in treating localized provoked vulvodynia. METHODS: Forty women with severe localized provoked vulvodynia were randomly and blindly assigned to self-administer either 40 mg enoxaparin or saline subcutaneously for 90 days. Dyspareunia and local sensitivity were evaluated before, at the end, and 90 days after treatment. The most painful focus was biopsied at the beginning of the study and a parallel site at the end of study for mast cells, PGP 9.5 nerve fiber staining, and heparanase quantification. RESULTS: The enoxaparin-treated women showed a greater reduction in vestibular sensitivity at the end of treatment and 3 months later (29.6% compared with 11.2%, P=.004). Seventy-five percent (15 of 20) of them reported more than 20% pain reduction compared with 27.8% (five of 18) in the placebo group (P=.004). Seven enoxaparin-treated women compared with three in the placebo group had almost painless intercourse at the end of the study. In women who had improvement of sensitivity at the site parallel to the original biopsy site, there was a histologically documented reduction in the number of intraepithelial-free nerve fibers in the enoxaparin group. CONCLUSION: Enoxaparin reduced the vestibular sensitivity and dyspareunia, concomitant with a reduction in intraepithelial free nerve fibers, in women with localized provoked vulvodynia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials. gov, NCT00874484. LEVEL OF EVIDENCE: I
BIOPESTICIDAL ACTIVITY OF Calotropis procera L. AGAINST Macrophomina phaseolina

Background: Mungbean [Vigna radiata (L.) Wilczek] is an important pulse crop globally. This imperative crop is severely affected by charcoal rot disease caused by Macrophomina phaseolina (Tassi) Goid. In the present study, the leaves of Calotropis procera L. were tested for their antifungal potential against M. phaseolina. Materials and Methods: Various concentrations i.e. 1%, 2.5%, 4%, 5.5% and 7% of methanolic extract of C. procera leaves were prepared and their in vitro bioactivity was examined against the test fungus. Methnolic leaf extract was partitioned using n-hexane, chloroform, ethyl acetate and n-butanol and antifungal activity of each fraction was evaluated. n-Hexane fraction was subjected to GC-MS analysis. Results: The higher concentration of methanolic leaf extract (7%) caused maximum inhibition in the diameter of M. phaseolina i.e. 38%. The n-hexane fraction of methanolic leaf extract was found to be the most effective against M. phaseolina. Seven compounds belonging to classes of chlorocarbon, aromatic hydrocarbon, azocompounds, aromatic carboxylic acids and fatty acids were identified in GC-MS analysis of n-hexane fraction. Conclusion: Antifungal activity of the methanolic leaf extract of C. procera might be due to the presence of the identified compounds in n-hexane fraction of methanolic leaf extract.
Three essays on pricing and volume distributions of cross-listed stocks

This dissertation provides empirical evidences in global cross-listed stocks trading volume and pricing. The first essay documents the global trading volume distribution of cross-listed stocks and examines factors that make a host market competitive in attracting order flows from the counterpart domestic market. The results show that host markets are more successful in attracting trading volume when they have a higher information factor, have lower bid-ask spreads, provide better investor protection and information disclosure, share the common language or legal origin with the counterpart home markets and locate closer to the home market. The second essay investigates the market competitiveness among rival host markets based on a unique sample of global firms simultaneously cross-listed in multiple foreign countries. I present the global cross-listings and trading volume distributions cross host-home markets as well as over time, and provide robust evidences that host markets are more successful in attracting trading volume from other competing markets when they have lower bid-ask spreads, better legal protection, more market liquidity, higher level of financial development, and where the firms with longer listing history. Interesting,
Expression of Th1 and Th2 Immunoregulatory Cytokines by Human Eosinophils

Besides cytotoxic mediators, human eosinophils can produce proinflammatory and anti–inflammatory cytokines, as well as growth factors and chemokines. The demonstration that eosinophils from patients could produce IL–5, IL–4 and IL–2 suggested their participation in the regulation of immune response. In the present work, we have examined the presence of Th1 (IFN–γ, IL–2) and Th2 (IL–4, IL–5, IL–10 and IL–13) cytokines in eosinophils from patients or donors by intracellular flow cytometry, and by immunocytochemistry. Whereas almost 100% eosinophils expressed intracellular IFN–γ, IL–2 and IL–10, the expression of IL–4, IL–5 and IL–13 is more variable and increased in patients versus donors. The differential release by eosinophils of Th2 versus Th1 cytokines is suggested both by the decrease of the intracellular content after culture, restricted to IL–4, IL–5 and IL–13, associated with an accumulation of IL–4 and IL–5 in the presence of Brefeldin. These results indicate that, through the preferential release of Th2 cytokines, human eosinophils can participate in the polarization of the immune response.
Mega-Events and Globalization: Capital and Spectacle in a Changing World Order

Since the turn of the twenty first century, there has been a trend for urban "mega events" to be awarded to cities and nations in the East and Global South. Such events have been viewed as economic stimulant as well as opportunities to promote national identity, gain greater international recognition and exercise a form of 'soft power. ' However, there has also been on-going controversy about the value, impact and legacy of global mega events in these cities and nations. This book provides a critical examination of the ambition for spectacle that has emerged across the East and Global South. The chapters explore the theoretical and conceptual issues associated with mega-events and new forms of globalization, from the critical political economy of mega-events in a changing world order to the contested social and economic legacies of mega-events and the widespread opposition that increasingly accompanies these events. The book also explores questions of urban development and governance, the role of new communications technologies in global economic expansion, the high security State, and the growing global influence of international non-governmental organizations. This book offers a rich collection of original theoretical contributions and global case studies from leading international scholars from the social sciences and humanities. It offers a fresh and unique interdisciplinary perspective that synthesizes cutting edge research on mega-events and urban spectacles while simultaneously contributing to a broader understanding of the dynamics of global capitalism and international political power in the early twenty first century.
Observability analysis and active control for airborne SLAM

An unmanned aerial vehicle (UAV) is tasked to explore an unknown environment and to map the features it finds, but must do so without the use of infrastructure-based localisation systems such as GPS, or any a priori terrain data. The UAV navigates using a statistical estimation technique known as simultaneous localisation and mapping (SLAM) which allows for the simultaneous estimation of the location of the UAV as well as the location of the features it sees. SLAM offers a unique approach to vehicle localisation with potential applications including planetary exploration, or when GPS is denied (for example under intentional GPS jamming, or applications where GPS signals cannot be reached), but more importantly can be used to augment already existing systems to improve robustness to navigation failure. One key requirement for SLAM to work is that it must reobserve features, and this has two effects: firstly, the improvement of the location estimate of the feature; and secondly, the improvement of the location estimate of the platform because of the statistical correlations that link the platform to the feature. So our UAV has two options; should it explore more unknown terrain to find new features, or should it revisit known features to improve localisation quality. These options are instantiated into the online path planner for the UAV. We present the SLAM algorithm and evaluate two important properties about the algorithm which assist in developing a path planning module for the UAV. The first of these is the use of the probabilistic measure of "entropy" as an information-based measure of the certainty in the map and vehicle locations, and is used as a utility function for planning the UAVs trajectory and determining the order in which features in the map are observed. The second is an observability analysis of SLAM which presents the unobservable states which are dependent on vehicle maneuvers. The analysis dictates the type of manoeuvres required by the UAV while observing features in order to maintain accurate statistical estimates of the map and vehicle location. This has the effect of reducing the action space that the path planner needs to search over. Using these two properties, we demonstrate an online path planner that intelligently plans the vehicle's trajectory while exploring unknown terrain in order to maximise the quality of both the map and vehicle location. Results of the online path planning algorithm are presented using a 6-DoF simulator of our UAV. The results show that the vehicle localisation errors are constrained and that the number of features and the size of the map steadily grows during the flight.
Does Lymphadenectomy Improve Survival in Uterine Leiomyosarcoma?

Introduction The role of lymphadenectomy in the management of uterine leiomyosarcoma (LMS) is controversial. We aimed to identify whether lymph node dissection (LND) has any survival benefit in uterine LMS. Methods Data of 95 patients with histologically proven uterine LMS from 2 tertiary centers (1993 through 2009) were retrospectively analyzed. Kaplan-Meier and Cox proportional hazards regression models were used for analyses. Results Mean age was 51.5 years. Thirty-six (37.9%) underwent LND. The median lymph node count was 54. Eight (22.2%) patients had lymphatic metastasis. Median follow-up was 26 months. Sixty-two (65%) patients had recurrence and 48 (50.5%) died. Median disease-free survival (DFS) was 19 months for both group of patients who had or did not have LND, and median overall survival (OS) was 29 and 26 months, respectively (P = 0.4). Five-year DFS was 35.9% vs 26.8% (P = 0.4), and 5-year OS was 45.4% vs 43.8% (P = 0.22) for the groups. Multivariate analyses did not reveal a single independent prognostic factor in respect to DFS or OS. Conclusion Higher rate of lymph node metastasis in patients with extrauterine disease indicated the importance of LND in LMS. However, the survival benefit of lymphadenectomy could not be shown.
HLA-class I antigens in patients with unexplained recurrent abortion

Abstract In order to clarify the genetic background of recurrent spontaneous abortion, the frequency of HLA-A, -B, and -C alleles was analyzed in eighty-nine patients with a history of unexplained primary recurrent abortion. The frequency of each HLA-A, -B, and -C antigen allele was calculated in patients with recurrent abortion and their husbands, and compared with the frequencies in the general population represented by 207 individuals in the Niigata district of Japan. The incidence of individuals homozygous for the HLA-A, -B, and -C alleles was also compared between the patient group and the control group. The frequency of HLA-B35 in the patient group (5 of 89, 5.6 %) was significantly lower than in the general population (40 of 207, 19.3 %) (Odds Ratio, 0.25; 95 % Confidence Interval, 0.0920.65; P < 0.005; Pc, not significant). The fre- quencies of other HLA-A, -B, and -C alleles were not significantly different between the patient group and the general population. No significant difference in the frequency of HLA-A, -B, and -C alleles was observed between the husband group and the general population. The incidence of individuals homozygous for HLA-A, -B, or -C alleles in the patient group was not significantly different from the general population. The significantly lower frequency of HLA-B35 in patients with unexplained recurrent abortion suggests that the Th2- associated immune reactions may be lacking in such patients, as it has been reported that an enhanced Th2 response in conjunction with a decreased T Th1 response is a common immune reaction in HLA-B35-positive individuals.
B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.

OBJECTIVES To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation. METHODS BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied. RESULTS A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 +/- 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 +/- 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data. CONCLUSIONS BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies.
Prognostic significance of serous and clear cell adenocarcinoma in surgically staged endometrial carcinoma

Background. The serous adenocarcinoma (SA) and clear cell adenocarcinoma (CCA) of endometrium have been shown to be associated with high relapse rate and poor survival. It is not clear whether prognostic significance of these specific cell types of tumor is independent of retroperitoneal lymph node metastasis and other histopathologic prognostic factors in endometrial carcinoma.
Management Strategies for Pyoderma Gangrenosum: Case Studies and Review of Literature

Pyoderma gangrenosum (PG) is a systemic disease with cutaneous manifestations consisting of necrotizing ulceration. The etiology of PG is controversial, and optimal management strategies have not been established. Current management is primarily medical to control the systemic inflammatory process, with occasional surgical intervention at the ulcer site. Based on the current literature and on the authors’ clinical experience, the optimal outcome depends on early diagnoses and a combination of medical and surgical therapy. Initial management is directed toward medical control of the inflammatory process and local wound care. Surgical strategies involve recipient site preparation via local wound care and serial allograft followed by autologous skin graft or muscle flap coverage when necessary. Long-term wound stabilization is obtained only through control of the systemic and local inflammatory process.