Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucocorticoid‐induced tumour necrosis factor receptor family‐related receptor signalling exacerbates hapten‐induced colitis by CD4+ T cells

The glucocorticoid‐induced tumour necrosis factor receptor family related gene (GITR) has been reported to be expressed on the activated T and CD4+CD25+ regulatory T cells (Treg). Signalling triggered by GITR not only neutralizes the suppressive effect of Treg cells, but also augments activation, proliferation and cytokine production of effector T cells. To test the role of GITR in 2,4,6‐trinitrobenzene sulphonic acid (TNBS)‐induced colitis − a murine model of mucosal inflammation − TNBS‐injected Balb/c mice were treated with agonistic anti‐GITR monoclonal antibody (mAb). Anti‐GITR treatment increased the death rate compared to rat IgG‐treated mice. Typically, death occurred within 4 days after the TNBS injection when the mice were treated with anti‐GITR. The mice that survived anti‐GITR treatment suffered from severe inflammation in their entire intestines. CD4+ T‐depletion protected the mice from colitis; even an anti‐GITR effect was not apparent. In contrast, CD8+ T depletion showed less protective than did CD4+ T depletion. Stimulation of GITR enhanced the production of proinflammatory cytokines including interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐12. It also enhanced the humoral response such as serum levels of IgG2b and IgA, which was completely dependent on CD4+ T cells. Taken together, this study demonstrated that GITR signalling on CD4+ T cells is involved in the development and progress of colitis by enhancing both T helper type 1 (Th1) and Th2 type responses.
Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease characterized by endocrine tumors of the parathyroids, the pancreatic islets, and the anterior pituitary. The MEN1 gene encodes menin, a nuclear protein interacting with JunD/AP1, Smad3, NFκB, and other proteins involved in transcription and cell growth regulation. Here, by exhaustive sequence analysis of 170 probands/families collected through a French clinical network, we identified 165 mutations located in coding parts of the MEN1 gene, which represent 114 distinct MEN1 germline alterations. These mutations have been included in a MEN1‐locus specific database available on the world wide web together with ≈240 germline and somatic MEN1 mutations listed from international published data. Our mutation series included 56 frameshifts, 23 nonsense, 27 missense, and eight deletion or insertion in‐frame mutations. Mutations were spread over the entire coding sequence. Taken together, most missense and in‐frame MEN1 genomic alterations affect one or all domains of menin interacting with JunD [codons 1–40; 139–242; 323–428], Smad3 [distal to codon 478], and NFκB [codons 276–479], three major effectors in transcription and cell growth regulation. No correlation has been observed between genotype and MEN1 phenotype. We suggest that the knowledge of structure and location of a specific mutation has not been useful in clinical practice for the follow‐up of affected patients and asymptomatic gene carriers. Our results provide the largest series of MEN1 mutations published to date. They will be a useful tool for further studies focusing on the functional effects of missense mutations and understanding which mechanisms or pathways related to multiple menin interactions might be involved in tumorigenesis of endocrine cells. © 2002 Wiley‐Liss, Inc.
Plerixafor on‐demand combined with chemotherapy and granulocyte colony‐stimulating factor: significant improvement in peripheral blood stem cells mobilization and harvest with no increase in costs

To date, no prospective study on Plerixafor ‘on‐demand’ in combination with chemotherapy and granulocyte colony‐stimulating factor (G‐CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on‐demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G‐CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34+ cells in peripheral blood was reduced by ‘on‐demand’ strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34+ cells 2 × 106/kg decreased from 20·9 to 4·0% (P = 0·0001). The on‐demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a ‘bias‐adjusted set of controls’. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G‐CSF, the ‘on‐demand’ use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.
A Framework for Developing a Curriculum Regarding Autism Spectrum Disorders for Primary Care Providers.

INTRODUCTION The prevalence of Autism Spectrum Disorders (ASDs) has increased and varies across age groups. Thus there is an increasing need for educational opportunities for General Practitioners (GPs) and other Primary Care providers to help in early identification and referral to specialist services. An earlier survey of GPs in New South Wales (Australia) demonstrated two broad domains for educational activities: (1) a general knowledge (important for early identification and referral) and (2) surveillance (important for ongoing management). AIM To seek further evidence to these domains and synthesize the important contents for educational programs for GPs. MATERIALS AND METHODS We conducted a (1) Confirmatory Factor Analysis (CFA) on our original survey data and (2) systematic review of the literature to identify important educational topics, using a life cycle approach. RESULTS CFA and literature review support theoretical framework of two domains. Alerts and red flags for ASDs, knowledge of simple surveillance tools, communication of diagnosis with parents, referral pathways particularly to speech pathologists before a formal diagnosis is confirmed, and appreciation of vulnerabilities for identifying supports were important in the general knowledge domain, while supporting the families through transition points such as from pre-school to school entry, secondary school and adolescence, role of psychopharmacology such as medications for sleep issues, and for common co-morbidities of anxiety were important in the surveillance dimension. CONCLUSION GP supervisors and medical and nursing educators can use findings from this paper for developing structured learning activities for training primary health care workforce regarding ASD's.
Cost-utility analysis of preoperative radiotherapy in patients with rectal cancer undergoing total mesorectal excision: a study of the Dutch Colorectal Cancer Group.

PURPOSE To compare the societal costs and the (quality-adjusted) life expectancy of patients with rectal cancer undergoing total mesorectal excision (TME) with or without short-term preoperative radiotherapy (5 x 5 Gy). PATIENTS AND METHODS We used a Markov model to project the clinical and economic outcomes of preoperative radiotherapy. Data on local recurrence rates, quality of life, and costs were obtained from the patients of a multicenter randomized clinical trial. In this trial, 1,861 patients with resectable rectal cancer from 108 hospitals were randomly assigned for TME surgery with or without preoperative radiotherapy. Outcome measures of the model were life expectancy, quality-adjusted life expectancy, lifetime costs per patient, and the incremental cost-effectiveness ratio. RESULTS The base case model estimates that the loss of quality of life due to preoperative radiotherapy is outweighed by the gain in life expectancy. Life expectancy increases by 0.67 years; quality-adjusted life expectancy, by 0.39 years; and costs, by $9,800 per patient. The corresponding cost-effectiveness ratio is $25,100 per quality-adjusted life year. Sensitivity analyses indicate that the cost-effectiveness ratio remains acceptable under a wide range of assumptions. CONCLUSION Assuming that the reduced local recurrence rate does lead to a survival advantage, the cost-utility analysis estimates that the improved survival outweighs the impaired quality of life and the increased costs. We conclude that short-term preoperative radiotherapy in patients with rectal cancer undergoing TME is both effective and cost-effective.
DAL PLURALISMO POLARIZZATO AL PLURALISMO MODERATO. IL MODELLO DI SARTORI E LA TRANSIZIONE ITALIANA

Introduzione Negli anni novanta, l'Italia è entrata in un processo di transizione che è ormai divenuto oggetto di un'abbondante letteratura nazionale e straniera. Piuttosto ovviamente, la natura di tale transizione è ben diversa da quelle dei paesi postcomunisti e, come ha opportunamente sottolineato Pasquino (1994; 1995), poco comparabile con altri precedenti storici. Anche la Francia, che questo autore considera il miglior termine di confronto, lo è in realtà assai relativamente sotto una varietà di punti di vista. Mentre infatti la Quarta e, per lungo tempo, anche la Quinta Repubblica sono rimasti classici casi di pluralismo polarizzato (Sartori 1982, 256–262), l'Italia degli anni novanta non può più essere definita tale, e proprio per questo (o, almeno, anche per questo) si è avviata alla presente transizione. Come è noto, inoltre, le riforme golliste investirono essenzialmente le principali istituzioni politiche della repubblica, ma lasciarono inalterati il subsistema burocratico e la struttura (centralizzata) dello Stato, che sono, invece, componenti tutt'altro che secondarie per comprendere il decorso e gli eventuali sbocchi della crisi italiana. Ma, infine, tale crisi si intreccia anche al declino dello Stato sociale e interventista, coinvolgendo la ridefinizione dei confini fra politica ed economia e il ruolo delle grandi organizzazioni degli interessi, sindacati in testa. Come dire che, oltre al sistema politico-istituzionale ed alla pubblica amministrazione, le relazioni industriali e i loro attori pubblici e privati rappresentano una terza dimensione di cambiamento, che altrove è stata poco importante (Francia), ovvero incomparabilmente diversa (regimi postcomunisti).
Single access point localisation for wearable wireless sensors

Knowledge of a subject's location and motion throughout an environment is of significant use to in-home health monitoring and activity recognition systems. This work develops a method of tracking a subject's location using the radio frequency (RF) signals emanating from wearable wireless sensors. It differs from other RF location tracking work in that it utilises the hardware which would already be deployed in a biomedical monitoring application. This is achieved by combining the RSSI (Received Signal Strength Indicator) and LQI (Link Quality Indicator) readings from a single basestation. It is shown that accuracy approaching that of a multiple basestation localisation deployment is achievable by using a suitable level of filtering. As a result of this work, location information can be more readily and cheaply incorporated into future biomedical monitoring applications.
Prevalence and risk factors of erectile dysfunction in Niger delta region, Nigeria.

BACKGROUND Erectile Dysfunction (ED) is one of the major social problems causing significant distress in men. Despite the increasing difficulty in management, knowledge, and understanding of factors responsible for its development are important for prevention and care. OBJECTIVES To assess the prevalence and risk factors for ED among men in Niger Delta Region of Nigeria, in order to determine its contextual variables. METHODS Subjects included 400 male patients attending the general outpatients' clinic (GOPC) of the University of Uyo Teaching Hospital. Respondents completed the abridged version of the International Index of Erectile Function (IIEF-5). RESULTS A total of 166 (41.5%) subjects had ED; 66 (16.5%) had mild; 32 (8.0%) mild to moderate; 24 (6.0%) moderate; while 45 (11.3%) had severe 37 (9.2%) resulted from hypertension and its medications; 29 (7.3%) from diabetes; 49 (12.2%) from a combination of both and their therapies (P=0.044); 24 (6.0%) had history of previous surgery; while for 27 (6.8%) it was from undiagnosed medical conditions (p=0.001). The ED increases with age and is more among married and educated men. CONCLUSION ED is a common problem among men in Niger Delta region. Therefore, efforts must be made to reduce the incidence by dealing with the factors responsible for its development.
Upstart Industrialization and Exports: Evidence from Japan, 1880–1910

Between 1880 and 1910, Japanese exports increased in volume, changed composition, and shifted from leading industrialized countries toward poorer Asian neighbors. Using a new dataset disaggregated by product and trade partner for the universe of Japanese exports, we find extensive margins accounted for 30 percent of export growth, with trade costs and market size associated with successful market entry. There was also considerable persistence in maintaining market presence and exit was rare. These stylized facts provide insight into both the country’s economic development, as reflected in its exported products, as well as the demand conditions of its trade partners.
Total Ionizing Dose Effects in Si-Based Tunnel FETs

Total ionizing dose (TID) effects in Si-based tunnel finite element transfers (FETs) were investigated for the first time. Under 10-keV X-ray irradiation environment, along with the increase in total dose, a shift of the transfer characteristics and an increase in the interface trap density could be observed. After irradiation at 1 Mrad (SiO2) (and higher dose), the threshold voltage and the band-to-band tunneling conduction were only modestly affected, despite the thick buried oxide (140 nm). In contrast, under the same bias and irradiation environment, a FDSOI nMOSFET fabricated with a similar process presented a more severe degradation, suggesting the robustness of TFETs against TID effects. The underlying mechanism was explored through device simulation and ascribed to be due to the peculiarity of the doping structures of TFETs.
Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram

Three recent observational studies reported that the risk of fatal overdose is greater with venlafaxine than SSRI use. It is not clear whether patient factors could account for this finding. We evaluated whether risk factors for suicide are more prevalent among patients prescribed venlafaxine than patients prescribed fluoxetine or citalopram.
Endoscopic Gastric Submucosal Transplantation of Islets (ENDO‐STI): Technique and Initial Results in Diabetic Pigs

The results of transplantation of human donor islets into the portal vein (PV) in patients with diabetes are encouraging. However, there are complications, for example, hemorrhage, thrombosis and an immediate loss of islets through the ‘instant blood‐mediated inflammatory reaction’ (IBMIR). The gastric submucosal space (GSMS) offers potential advantages. Islets were isolated from adult pigs. Recipient pigs were made diabetic by streptozotocin. Donor islets were injected into the GSMS through a laparotomy (Group 1A, n = 4) or endoscopically (Group 1B, n = 8) or into the PV through a laparotomy (Group 2, n = 3). The pigs were followed for a maximum of 28 days. Monitoring of C‐peptide in Group 1 indicated that there was minimal immediate loss of islets whereas in Group 2 there was considerable loss from IBMIR. In Group 1, there were significant reductions in mean blood glucose and mean exogenous insulin requirement between pretransplantation and 20 days posttransplantation. In Group 2, there was no significant reduction in either parameter. Insulin‐positive cells were seen in the GSMS in Group 1, but not in the liver in Group 2. Endoscopic gastric submucosal transplantation of islets (ENDO‐STI) offers a minimally invasive and quick approach to islet transplantation, avoids IBMIR and warrants further exploration.
Clinical severity of ischemic stroke and neural damage biomarkers in the acute setting: the STROke MArkers (STROMA) study.

BACKGROUND Stroke is a leading cause of long-term morbidity and mortality affecting several hundred-thousand people annually in the Western Countries. Various panels of biomarkers of neural damage have been developed and validated. The primary objective of this investigation was to measure the correlation between the clinical severity of stroke and the serum/plasma concentrations of neural damage biomarkers. METHODS A prospective investigation was conducted on a panel of biomarkers composed of S100β, matrix metalloproteinase-9 (MMP-9), N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and D-dimer at admission and after 24 hours, in a cohort patients with a confirmed diagnosis of stroke in an emergency setting (STROke-MArkers STROMA). RESULTS A total of 58 consecutive patients were enrolled, no participant was excluded; according to clinical severity measured by National Institute of Health Stroke Scale (NIHSS) there were 29 minor strokes, 24 moderate, 3 moderate-severe, 2 severe. The Spearman's rank correlation test was used to assess the relationship between the baseline NIHSS value and the concentrations of the four biomarkers: all the studied biomarkers showed a statistically significant correlation with baseline NIHSS at 24 hours. A multivariate ordinal regression model was used to analyze the correlation of markers with stroke severity, stratified, according to NIHSS score: MMP-9 and S100β showed a statistically significant correlation after 24 hours. CONCLUSION MMP-9, S100β, NT pro-BNP and D-dimer showed a good correlation with the clinical severity of stroke which may become an additional resource in the acute patient evaluation and potentially follow-up.
Provider Characteristics Desired by African American Women in Prenatal Care

Purpose: The purpose of this study was to describe provider characteristics African American pregnant women identified as important when interacting with their prenatal care providers in an outpatient office setting. Study Design and Method: A descriptive qualitative design was used to explore provider characteristics desired by African American women receiving prenatal care at two inner-city hospital—based obstetric clinics. A total of 22 African American women between the ages of 19 and 28 years participated in the study. Findings: Four major provider characteristic themes emerged from the data: (a) demonstrating quality patient—provider communication, (b) providing continuity of care, (c) treating the women with respect, and (d) delivering compassionate care. Discussion and Conclusion: An overarching theme revealed by the data analysis was the desire by African American women in this study to have their prenatal providers know and remember them. They wanted their providers to understand the context of their lives from their prenatal interactions. Incorporating findings from this study to improve patient—provider interactions during prenatal care could provide an increased understanding of the many complex variables affecting African American women’s lives. Implications for Practice and Research: Prenatal care provides an opportunity for African American women to develop a trusting relationship with a provider. Developing models of prenatal care congruent with the realities of African American women’s lives has the potential to improve patient— provider interactions and potentially affect birth outcomes.
Patterns of Male Reproductive Success in Crepidula fornicata Provide New Insight for Sex Allocation and Optimal Sex Change

The size-advantage model and sex-allocation theory are frequently invoked to explain the evolution and maintenance of sequential hermaphroditism in many taxa. A test of current theory requires quantitative estimates of reproductive success and knowledge of the relationship between reproduction and size for each gender. Reproductive success can be difficult to measure. In species where polyandry occurs, it can be quantified only by determining paternity of offspring. We employed microsatellite loci to establish paternity for 12 families of Crepidula fornicata, where a family is defined as a single female, her brood, and the males stacked on top of her. Genetic data were analyzed and paternity was assigned to a single potential father for more than 83% of the offspring tested. Estimates of reproductive success revealed that one male within the family fathered the majority of offspring and that he was usually the largest male and the one closest to the brooding female. The dominant male's success also tended to decrease as the number of mature males within the family increased. Our results suggest that sperm competition could be a driving force in determining male reproductive success and the timing of sex change in C. fornicata.
The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids.

OBJECTIVE To evaluate the effect of maternally derived antibody on the immunogenicity and reactogenicity of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS A total of 2342 infants were randomized to receive one of 13 DTaP or 2 DTP vaccines at 2, 4, and 6 months of age. The correlation between preimmunization and postimmunization antibody after three doses of vaccine and the relation between preimmunization antibody and adverse reactions after the first immunization were modeled by linear regression. RESULTS After DTP but not DTaP, higher levels of preexisting antibody were associated with substantial (28% to 56%) reductions in the subsequent antibody response to pertussis toxin (PT). For other pertussis antibodies, modest inverse correlations were seen between preexisting antibody concentrations and most postimmunization antibody responses (resulting in 8% to 18% reductions in postimmunization antibody) for both DTP and DTaP. There was no consistent association in any DTP or DTaP group between adverse reactions and preimmunization antibody levels. CONCLUSION The PT antibody response to DTaP, unlike DTP, is not adversely affected by preexisting antibody to PT. Inhibitory effects with respect to other antibodies, seen with both DTP and DTaP, were relatively modest. Our data suggest that the use of acellular pertussis vaccines in adults, which could confer higher levels of antibody in women before pregnancy, would be unlikely to adversely affect pertussis antibody responses after DTaP among infants born to mothers with high antibody levels.