Miracle-dz/UniFAR-FTUs huggingface dataset:
SPATA2 links CYLD to the TNF‐α receptor signaling complex and modulates the receptor signaling outcomes

TNF‐α is a key regulator of innate immune and proinflammatory responses. However, the composition of the TNF‐α receptor‐associated signaling complexes (TNF‐RSC) and the architecture of the downstream signaling networks are incompletely understood. We employed quantitative mass spectrometry to demonstrate that TNF‐α stimulation induces widespread protein phosphorylation and that the scope of phosphorylation expands in a temporal manner. TNF‐α stimulation also induces rapid ubiquitylation of components of the TNF‐RSC. Temporal analysis of the TNF‐RSC composition identified SPATA2 as a novel component of the TNF‐RSC. The predicted PUB domain in the N‐terminus of SPATA2 interacts with the USP domain of CYLD, whereas the C‐terminus of SPATA2 interacts with HOIP. SPATA2 is required for recruitment of CYLD to the TNF‐RSC. Downregulation of SPATA2 augments transcriptional activation of NF‐κB and inhibits TNF‐α‐induced necroptosis, pointing to an important function of SPATA2 in modulating the outcomes of TNF‐α signaling. Taken together, our study draws a detailed map of TNF‐α signaling, identifies SPATA2 as a novel component of TNF‐α signaling, and provides a rich resource for further functional investigations.
Impact of the Karnofsky Performance Status on Survival and its Dynamics During the Terminal Year of Peritoneal Dialysis Patients

Background: Simple and low-cost tools to monitor the risk profile of patients on peritoneal dialysis (PD) at high risk of complications and mortality are scarce. One of the tools available to monitor the variation in vitality and dependence levels is the Karnofsky performance status (KPS). This study analyzed the average trends and variation of KPS during the 12 months before death and its independent value in predicting patients' survival. Methods: The data were compiled from the BRAZPD II multicenter study, performed in Brazil between 2004 and 2011. For the analysis of KPS dynamics, we included patients with at least 12 months of follow-up on PD and who had a fatal event during the follow-up. The following covariables were evaluated: age, gender, ethnicity, educational level, and presence of diabetes. We used the linear regression model to present the results: the log (time) before death was represented by the regression variable and KPS was the response. We also analyzed the independent impact of baseline KPS on patients' survival. Results: From the population of 9,905 patients enrolled in the BRAZPD study, 4,133 survived 12 months on PD and were included in the analysis. There was a gradual decline in the KPS scores, which accelerated in the last 2 months before death. These changes were similar irrespective of age, race, family income, gender, diabetes, PD modality, and education level. We observed 989 fatal events in this population during the observation period, and the KPS score was identified as an independent predictor for mortality in this cohort. Conclusions: This study demonstrates for the first time the dynamics of KPS before death in PD patients, indicating a progressive and accelerated decline of KPS in the 12 months before patients died. In addition, KPS was an independent predictor of mortality in this population.
Incidence of Parkinson disease and parkinsonism in three elderly populations of central Spain

Background: A two-phase investigation method (screening followed by detailed examination) is the most accurate epidemiologic approach to estimate the epidemiology of Parkinson disease (PD) and secondary parkinsonism. The scarcity of statistics on the incidence of PD and other types of parkinsonism using this methodology led the authors to estimate them in three elderly populations. Methods: A Spanish elderly parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were contacted by way of screening and clinical examination. Results: The cohort consisted of 5,160 subjects (ages 65 to 85 and over): Eight hundred twenty-eight died before the examination, 3,685 completed the screening procedure, and 647 could not be screened because they refused (108) or were unreachable (539). Sixty-eight incident cases of parkinsonism were found: 30 PD (44.1%), 22 drug-induced parkinsonism (32.3%), 8 parkinsonism with associated features (11.7%), and 3 vascular parkinsonism (4.4%). The remaining five cases (7.3%) were classified as unspecified parkinsonism. Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 85 and over years, adjusted to the standard European population, was 409.9 (95% CI 299.0 to 520.8) for parkinsonism and 186.8 (95% CI 110.4 to 263.2) for PD. Incidence rates of parkinsonism increased with advancing age. For PD, incidence rates increased with age in men but decreased beyond the age of 79 in women. Age-adjusted relative risk in men compared with women was 1.56 (95% CI 0.97 to 2.51) for parkinsonism and 2.55 (95% CI 1.21 to 5.37) for PD. Sixteen (53.3%) patients with PD were detected through the screening and had not been diagnosed previously. Conclusions: Incidence estimates of PD based on two-phase investigation methodology are higher than those based on other approaches. Men had a risk of developing PD that was twice that of women. A large proportion of PD patients may never seek neurologic attention.
Spatial optimization in perfusion bioreactors improves bone tissue‐engineered construct quality attributes

Perfusion bioreactors have shown great promise for tissue engineering applications providing a homogeneous and consistent distribution of nutrients and flow‐induced shear stresses throughout tissue‐engineered constructs. However, non‐uniform fluid‐flow profiles found in the perfusion chamber entrance region have been shown to affect tissue‐engineered construct quality characteristics during culture. In this study a whole perfusion and construct, three dimensional (3D) computational fluid dynamics approach was used in order to optimize a critical design parameter such as the location of the regular pore scaffolds within the perfusion bioreactor chamber. Computational studies were coupled to bioreactor experiments for a case‐study flow rate. Two cases were compared in the first instance seeded scaffolds were positioned immediately after the perfusion chamber inlet while a second group was positioned at the computationally determined optimum distance were a steady state flow profile had been reached. Experimental data showed that scaffold location affected significantly cell content and neo‐tissue distribution, as determined and quantified by contrast enhanced nanoCT, within the constructs both at 14 and 21 days of culture. However, gene expression level of osteopontin and osteocalcin was not affected by the scaffold location. This study demonstrates that the bioreactor chamber environment, incorporating a scaffold and its location within it, affects the flow patterns within the pores throughout the scaffold requiring therefore dedicated optimization that can lead to bone tissue engineered constructs with improved quality attributes. Biotechnol. Bioeng. 2014;111: 2560–2570. © 2014 Wiley Periodicals, Inc.
Infectious agents and lymphoma development: molecular and clinical aspects

This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT)‐type. Some paradigmatic examples of these associations include the Helicobacter pylori‐related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well‐documented association between Epstein–Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.
Cervical and Ocular Vestibular Evoked Myogenic Potentials Are Sensitive to Stimulus Phase

Sinusoidal forces with frequencies of 100 and 500 Hz and initial positive or negative polarities were delivered to the mastoids and Fz in normal subjects. We investigated whether the cVEMPs and oVEMPs evoked were sensitive to the polarity (phase) of vibration. With mastoid stimulation at 100 Hz, medial head acceleration produced cVEMPs with earlier latency (15.5 ms) than lateral acceleration (19.7 ms) and oVEMPs with later latency (13.8 ms) than lateral acceleration (10.6 ms). As the stimulus frequency increased, the difference in latency decreased, but was still present at 500 Hz. A similar pattern occurred following stimulation at Fz. Our results show that the initial direction of bone-conducted vibration affects both cVEMP and oVEMP properties even at relatively high frequencies.
Educational Technology Infrastructure and Services in North American Medical Schools

Purpose To describe the current educational technology infrastructure and services provided by North American allopathic medical schools that are members of the Association of American Medical Colleges (AAMC), to present information needed for institutional benchmarking. Method A Web-based survey instrument was developed and administered in the fall of 2004 by the authors, sent to representatives of 137 medical schools and completed by representatives of 88, a response rate of 64%. Schools were given scores for infrastructure and services provided. Data were analyzed with one-way analyses of variance, chi-square, and correlation coefficients. Results There was no difference in the number of infrastructure features or services offered based on region of the country, public versus private schools, or size of graduating class. Schools implemented 3.0 (SD = 1.5) of 6 infrastructure items and offered 11.6 (SD = 4.1) of 22 services. Over 90% of schools had wireless access (97%), used online course materials for undergraduate medical education (97%), course management system for graduate medical education (95%) and online teaching evaluations (90%). Use of services differed across the undergraduate, graduate, and continuing medical education continuum. Outside of e-portfolios for undergraduates, the least-offered services were for services to graduate and continuing medical education. Conclusions The results of this survey provide a benchmark for the level of services and infrastructure currently supporting educational technology by AAMC-member allopathic medical schools.
Genetically Linked Site‐Specificity of Disuse Osteoporosis

The genetic influence on bone loss in response to mechanical unloading was investigated within diaphyseal and distal femoral regions in three genetically distinct strains of mice. One mouse strain failed to lose bone after removal of function, whereas osteopenia was evident in multiple regions of the remaining two strains but in different areas of the bone.
Middle cerebral artery variations: duplicated and accessory arteries.

PURPOSE Our goal was to analyze the anatomic similarity between the duplicated middle cerebral artery (MCA) and the accessory MCA and their relationship to the early branches of the MCA. METHODS We reviewed stereoscopic angiograms of duplicated MCAs in four patients and accessory MCAs in four patients with reference to the origin, size, and cortical supply of these anomalous vessels, along with the presence of perforating arteries and the recurrent artery of Heubner (RAH). RESULTS The duplicated MCAs supplied the cortical territory of the temporopolar and the anterior temporal and/or middle temporal arteries. The accessory MCAs supplied the cortical territory of the orbitofrontal and/or prefrontal arteries. The duplicated MCAs had perforating arteries in three of four cases and coexisted with the RAH in three of four cases, whereas the main MCA had perforating arteries in all four cases. The accessory MCA had perforating arteries in all four cases and coexisted with the RAH in three of four cases, whereas the main MCA had perforating arteries in one of four cases. CONCLUSION A consistent cortical supply by the duplicated MCA and the accessory MCA to the anterior temporal lobe and the anterior frontal lobe, respectively, and its similarity to the cortical supply by the early branches of the MCA suggest that development of duplicated and/or accessory MCAs is an anomalously early ramification of the early branches of the MCA.
Significant Contribution of the Portal Vein to Blood Flow Through the Common Bile Duct

Objective:The aim of this study was to determine the contribution of the hepatic artery, gastroduodenal artery, and portal vein to the microvascular blood flow in the common bile duct (CBD). Background:Biliary complications are a common cause of graft loss after liver transplantation. The occurrence is, partly, attributed to hepatic artery thrombosis, which is considered to be the sole provider of blood flow to the bile ducts. However, the contribution of the portal vein and the gastroduodenal artery to the bile ducts is unknown. Methods:Microvascular blood flow in the CBD was determined in 15 patients who underwent a pancreaticoduodenectomy with a combination of laser Doppler flowmetry and reflectance spectrophotometry. Microvascular blood flow was measured at baseline, during clamping the portal vein, during clamping the hepatic artery, and during clamping both. After transection of the CBD, these 4 measurements were repeated. Results:Compared with baseline measurements, the microvascular blood flow through the CBD decreased to 62% after clamping the portal vein, 51% after clamping the hepatic artery, and 31% after clamping both. After the CBD was transected, these 3 measurements were 60%, 31%, and 20%, respectively. Conclusions:Historically, the hepatic artery has been considered mainly responsible for biliary blood flow. We show that after transection of the CBD, mimicking the situation after liver transplantation, the contribution of the portal vein to the microvascular blood flow through the CBD is 40%. This study emphasizes the importance of the portal vein, and disturbances in portal venous blood flow could contribute to the formation of biliary complications after liver transplantation.
Cruise Passengers’ Intention and Sustainable Management of Cruise Destinations

Recent tourism studies have shown that cruise passengers´ intention can be used as a tool to evaluate the sustainability of port of call destination. However, studies on this topic remain scarce and only offer an initial conceptualization of this issue. Hoping to help fill this void, the present research proposes a robust model for the analysis of the cruise passengers´ intention as assessed by Partial Least Squares. Data was collected in the port of Malaga (Spain), between January and December 2018. The results showed that reputation and familiarity are the best explanatory factors of the cruise passengers´ intention with a port of call destination. Also, cognitive perception and affective evaluation are the antecedents of reputation and familiarity.
Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival

Background & Aims The immunological microenvironment of HCC influences patient outcome, however, the role of B cells remains unclear. This study investigated effects of local B-cell infiltration in HCC cohorts on patient survival and immunological and molecular tumor microenvironment. Results Unsupervised gene expression analysis of full cancer transcriptomes (N=2158) revealed a highly co-regulated immunological cluster in HCC that mainly contained immunoglobulin fragments. More specifically, in an independent patient cohort (N=242) that compares HCC with non tumorous liver tissue high expression of these B-cell associated genes was associated with better patient outcome (P=0.0149). Conclusively, the immunohistochemical analysis of another independent cohort of resected HCCs (N=119) demonstrated that infiltration of HCCs by CD20+ cells (P=0.004) and CD79a+ cells (P=0.038) at the infiltrative margin were associated with prolonged patient survival. Further, the immunoglobulin fragments that were identified in the gene expression analysis were detected at high levels in patients with dense B-cell infiltration. Methods Gene expression of 2 independent HCC tissue databases was compared using microarrays. Additionally, tissue of resected HCCs was stained for CD20, CD79a and immunoglobulins and analysed for the respective cell numbers separately for tumor, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Conclusions Infiltration of HCCs by B cells is associated with prolonged patient survival. Further, a distinct B-cell like immunoglobulin profile of HCCs was identified that goes along with better patient outcome. We suggest that B cells contribute to local tumor control by secreting increased levels of immunoglobulins with antitumor activity.
Studies on the Safety of Glucose and Paraben-Containing Neostigmine for Intrathecal Administration

Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 micro g, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine. (Anesth Analg 1997;85:317-23)
Residents’ Perceptions of Tourism Impact on Community in National Parks in Serbia

Abstract The research involved a comparison of two case studies dealing with the perceptions of the local population to tourism. The effects and the control of tourism development were analyzed, as well as the availability of information on sustainable tourism and impact on the community in two national parks (NPs) in Serbia. The survey method was applied on a sample of 227 (NP Đerdap) and 210 (NP Tara) respondents. The survey results identified the strong positive perception of the presence of tourists among the two categories of respondents and also certain differences regarding economic benefits of tourism. Research also recognized a poor impact of tourism on the local community in terms of their knowledge and personal involvement. Education and employment in tourism industry were found to be strong factors affecting the residents’ perceptions. Some independent variables significantly predicted the level of local population’s support for tourism in both national parks (tourism impact on job creation, tourism impact on fostering a local culture, etc.). This comparative analysis provides inputs for directing future tourism programmes and devising a development policies adjusted to the needs of the local community.
Quantitative multiplexed analysis of ErbB family coexpression for primary breast cancer prognosis in a large retrospective cohort

Assessment of outcome using a single prognostic or predictive marker is the current basis of targeted therapy, but is inherently limited by its simplicity. Multiplexing has provided better classification, but has only been done quantitatively using RNA or DNA. Automated quantitative analysis is a new technology that allows quantitative in situ assessment of protein expression. The authors hypothesized that multiplexed quantitative measurement of ErbB receptor family proteins may allow better prediction of outcome.
A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion

Abstract Background: Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. Objective: Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). Methods: A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. Results: The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post-TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. Conclusion: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.
Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase expression in tumor tissue, regarding the efficacy of postoperatively administered UFT (tegafur+uracil) in patients with non-small cell lung cancer.

BACKGROUND UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined. PATIENTS AND METHODS Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined. RESULTS There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis. CONCLUSION The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.