Miracle-dz/UniFAR-FTUs huggingface dataset:
TAP deficiency syndrome

Bare lymphocyte syndrome (BLS) is characterized by a severe down-regulation of HLA class I and/or class II molecules. In type 1 BLS the defect is confined to HLA class I molecules, while in type 2 BLS HLA class II molecules are down-regulated [1]. Characterization of 22 patients with type 1 BLS over the last 22 years has revealed the existence of several clinically and immunologically distinct disease subsets [1–20]. In this review we will focus on a recently characterized group of patients with a distinct disease phenotype due to a defective TAP complex, the peptide transporter complex associated with antigen presentation [2–15]. We will describe clinical manifestations and immunological findings of patients suffering from TAP deficiency syndrome, and discuss the differential diagnosis and therapeutic options.
VISUAL OUTCOME AFTER CONGENITAL CATARACT SURGERY . LONG-TERM CLINICAL RESULTS

The results of congenital cataract extraction were evaluated in 108 patients (163 eyes) who underwent cataract surgery at the Department of Paediatric Opthalmology between 1985 and 1998. The outcome was assessed in terms of postoperative visual acuity and binocular vision. Fifty-one percent of the patients with bilateral aphakia and 47% with bilateral intraocular lens (IOL) implantation had a Snellen visual acuity of 0.5 or higher on the last visit. Similar values were achieved in 36% and 61% of the patients with unilateral aphakia and IOL implantation, respectively. In the patients who wore contact lenses after surgery, 29 % of those with bilateral cataract and 18 % of those with unilateral cataract attained fusion or stereopsis. Eleven of the 17 patients with unilateral cataract who had primary IOL implantation by 6 months of age achieved stereopsis. We conclude that surgery and optical correction should be performed at a very early age, i.e., in the sensitive period of binocular visual development, especially if dense opacities are present. With late surgery, good outcomes are achieved in the eyes in which opacity is only partial or is low in density. The importance of consistent visual rehabilitation and occlusion therapy of the involved eye for the treatment of amblyopia is emphasised.
Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT)

Background— This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results— Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P<0.001) lower in LBBB patients (0.47; P<0.001) than in non-LBBB patients (1.24; P=0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P<0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients. Conclusions— Heart failure patients with New York Heart Association class I or II and ejection fraction ⩽30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances). Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00180271.
The Impact of Supply Network Structure on the Financial Performance of the Firm

Supply chain finance (SCF) as a topic of academic interest and professional practice is rather nebulous, in the sense that the financial aspects of the supply chain have far reaching and complex effects on the entire enterprise. Firms that properly manage their SCF initiatives experience significant benefits to market capitalization and cash flow performance throughout the extended enterprise. Additionally, recent research has emerged that conceptualizes supply chains under the guise of networks. However, even with the important role that SCF plays throughout the supply network, there has been little research that specifically examines the characteristics of a firm’s supply network structure and its impact on financial performance. Consequently there is a gap in the literature dealing with this relationship and thus the primary undertaking in this research is to answer the following research question: what role does a firm’s supply network structure have in explaining its financial performance? We estimate several random effects GLS regressions to test several theoretically driven hypotheses. Our results suggest that firms that can understand and optimize their network structures can use them to their advantage to generate significant improvements in ROA, ROI, ROE, and ROS.
Paracetamol for the Treatment of Patent Ductus Arteriosus in Very Low Birth Weight Infants

Persistent patent ductus arteriosus (PDA) is associated with significant co-morbidities and increased mortality in preterm infants, especially very low birth weight (VLBW) infants. A large number of studies on the management of PDA have been published. Despite PDA being such a common condition in preterm infants, there is no consensus on which PDAs to treat, when to treat and how best to treat. Nonspecific cyclo-oxygenase inhibitors such as indomethacin and ibuprofen have been the mainstay of medical treatment of PDA for decades. Ibuprofen has similar efficacy and higher safety profile when compared to indomethacin, as it is associated with fewer gastrointestinal and renal side effects, and is considered the drug of choice for PDA closure. Recently, there is a growing interest in paracetamol for PDA closure and it has been suggested as an alternative drug to treat PDA. Finding the optimal pharmacological treatment for PDA closure in VLBW continues to remain challenging. In this review article, we assessed the evidence of paracetamol for PDA closure VLBW infants.
Capturing the electromagnetic counterparts of binary neutron star mergers through low-latency gravitational wave triggers

We investigate the prospects for joint low-latency gravitational wave (GW) detection and prompt electromagnetic (EM) follow-up observations of coalescing binary neutron stars (BNSs). For BNS mergers associated with short duration gamma-ray bursts (SGRBs), we for the first time evaluate the feasibility of rapid EM follow-ups to capture the prompt emission, early engine activity or reveal any potential by-products such as magnetars or fast radio bursts. To achieve our goal, we first simulate a population of coalescing BNSs using realistic distributions of source parameters and estimate the detectability and localisation efficiency at different times before merger. We then use a selection of facilities with GW follow-up agreements in place, from low-frequency radio to high energy γ-ray to assess the prospects of prompt follow-up. We quantify our assessment using observational SGRB flux data extrapolated to be within the horizon distances of the advanced GW interferometric detectors LIGO and Virgo and to the prompt phase immediately following the binary merger. Our results illustrate that while challenging, breakthrough multi-messenger science is possible with EM followup facilities with fast responses and wide fields-of-view. We demonstrate that the opportunity to catch the prompt stage (< 5s) of SGRBs, can be enhanced by speeding up the detection pipelines of both GW observatories and EM follow-up facilities. We further show that the addition of an Australian instrument to the optimal detector network could possibly improve the angular resolution by a factor of two and thereby contribute significantly to GW-EM multi-messenger astronomy.
Substrate source use in older, trained males after decades of endurance training.

PURPOSE The purpose of this study was to compare substrate source use in older, long-term exercising, endurance-trained males with sedentary controls. METHODS [U-C]palmitate and [6,6-H2]glucose tracers were applied to assess plasma free fatty acid (FFA) and glucose oxidation rates, and to estimate muscle- and/or lipoprotein-derived triacylglycerol (TG) and muscle glycogen use. Subjects were 10 long-term exercising, endurance-trained males and 10 sedentary controls (age 57 +/- 1 and 60 +/- 2 yr, respectively). Muscle biopsy samples were collected before and after exercise to assess muscle fiber type-specific intramyocellular lipid and glycogen content. RESULTS During exercise, plasma palmitate Ra, Rd, and Rox were significantly greater in the trained subjects compared with the controls (Ra: 0.36 +/- 0.02 and 0.25 +/- 0.02; Rd: 0.36 +/- 0.03 and 0.24 +/- 0.02; Rox: 0.31 +/- 0.02 and 0.20 +/- 0.02 mmol.min, respectively, P < 0.01). This resulted in greater plasma FFA and total fat oxidation rates in the trained versus sedentary subjects (P < 0.001). Muscle- and/or lipoprotein-derived TG use contributed 10 +/- 2 and 11 +/- 3% in the trained and control groups, respectively (NS). No significant net changes in muscle fiber lipid content were observed. CONCLUSIONS Older, endurance-trained males oxidize more fat during moderate-intensity exercise than do sedentary controls. This greater total fat oxidation rate is attributed to a higher plasma FFA release, uptake, and oxidation rate. In contrast, intramyocellular triacylglycerol does not seem to represent a major substrate source during 1 h of moderate-intensity exercise in older trained or sedentary men.
Transformer oil DGA monitoring technology study 2015

As use of dissolved gas analysis (DGA) monitors increases as a growing component of transformer maintenance and reliability, it is imperative to understand the capabilities of monitors in their ability to align with conventional laboratory results and detect gas-related changes from a baseline. SDMyers studied DGA monitors from several manufacturers through experiments over 18 months. Technologies included in the study were gas chromatography, photo-acoustic spectroscopy, solid-state palladium, thermal conductivity detection, and selective membrane methods. This paper summarizes conclusions from that study based on technology employed.
Interaction of a GRB-IR Splice Variant (a Human GRB10 Homolog) with the Insulin and Insulin-like Growth Factor I Receptors

We have utilized the yeast two-hybrid system to identify proteins that interact with the cytoplasmic domain of the insulin receptor. We identified a human cDNA that is a splice variant of the human GRB10 homolog GRB-IR, which we term GRB10/IR-SV1 (for GRB10/GRB-IR splice variant 1). The protein encoded by the GRB10/IR-SV1 cDNA contains an SH2 domain and a pleckstrin homology domain. Cloning of a full-length human cDNA revealed a predicted coding sequence that was similar to the mouse GRB10 protein, although GRB10/IR-SV1 contained an 80-amino acid deletion. The GRB10/IR-SV1 cDNA is a splice variant of the GRB-IR cDNA such that GRB10/IR-SV1 contains an intact pleckstrin homology domain and a distinct amino terminus. The interaction of GRB10/IR-SV1 with the insulin receptor and the insulin-like growth factor I (IGF-I) receptor is mediated by the SH2 domain, and we show that glutathione S-transferase-SH2 domain fusion proteins interact specifically in vitro with the insulin receptor derived from mammalian cells. The GRB10/IR-SV1 SH2 domain also interacted with an ∼135-kDa phosphoprotein from unstimulated cell lysates, an interaction that decreased after insulin stimulation. We present evidence that the GRB10/IR-SV1 protein plays a functional role in insulin and IGF-I signaling by showing that microinjection of an SH2 domain fusion protein inhibited insulin- and IGF-I-stimulated mitogenesis in fibroblasts, yet had no effect on mitogenesis induced by epidermal growth factor. Our findings suggest that GRB10/IR-SV1 may serve to positively link the insulin and IGF-I receptors to an uncharacterized mitogenic signaling pathway.
The role of education in explaining and forecasting trends in functional limitations among older Americans*

Using the Survey of Income and Program Participation, we document the importance of education in accounting for declines in functional limitations among older Americans from 1984 to 1993. Of the eight demographic and socioeconomic variables considered, education is most important in accounting for recent trends. The relationship between educational attainment and functioning has not changed measurably, but educational attainment has increased greatly during this period. Our analysis suggests, all else being equal, that future changes in education will continue to contribute to improvements in functioning, although at a reduced rate.
Preclinical In Vivo Modeling of Cytokine Release Syndrome Induced by ErbB-Retargeted Human T Cells: Identifying a Window of Therapeutic Opportunity?

The ErbB network is dysregulated in many solid tumors. To exploit this, we have developed a chimeric Ag receptor (CAR) named T1E28z that targets several pathogenetically relevant ErbB dimers. T1E28z is coexpressed with a chimeric cytokine receptor named 4αβ (combination termed T4), enabling the selective expansion of engineered T cells using IL-4. Human T4+ T cells exhibit antitumor activity against several ErbB+ cancer types. However, ErbB receptors are also expressed in several healthy tissues, raising concerns about toxic potential. In this study, we have evaluated safety of T4 immunotherapy in vivo using a SCID beige mouse model. We show that the human T1E28z CAR efficiently recognizes mouse ErbB+ cells, rendering this species suitable to evaluate preclinical toxicity. Administration of T4+ T cells using the i.v. or intratumoral routes achieves partial tumor regression without clinical or histopathologic toxicity. In contrast, when delivered i.p., tumor reduction is accompanied by dose-dependent side effects. Toxicity mediated by T4+ T cells results from target recognition in both tumor and healthy tissues, leading to release of both human (IL-2/IFN-γ) and murine (IL-6) cytokines. In extreme cases, outcome is lethal. Both toxicity and IL-6 release can be ameliorated by prior macrophage depletion, consistent with clinical data that implicate IL-6 in this pathogenic event. These data demonstrate that CAR-induced cytokine release syndrome can be modeled in mice that express target Ag in an appropriate distribution. Furthermore, our findings argue that ErbB-retargeted T cells can achieve therapeutic benefit in the absence of unacceptable toxicity, providing that route of administration and dose are carefully optimized.
THE EFFECT OF RESPIRATORY SYNCTIAL VIRUS ON CHEMOKINE RELEASE BY DIFFERENTIATED AIRWAY EPITHELIUM

Respiratory synctial virus (RSV) infection of undifferentiated airway epithelial cells has been shown to induce the production of chemokines. The purpose of this study was to investigate the vectorial release of interleukin (IL-8) and Released on Activation, Normal T-cell Expressed and Secreted (RANTES) by polarized, well-differentiated respiratory epithelial cells after RSV infection. Human bronchial epithelial cultures were differentiated under air-liquid interface conditions and infected with RSV by the apical or basolateral route. RSV infection was specific to the apical surface. Supernatants were collected at 6 and 48 hours after RSV inoculation, and IL-8 and RANTES were measured by enzyme-linked immunosorbent assay (ELISA). Both IL-8 and RANTES were significantly released by 48 hours following inoculation with RSV. The secretion of each chemokine was greatest after apical inoculation, and secretion was polarized to the basolateral supernatant. Immunohistochemical staining confirmed that RSV infection was specific to ciliated cells, and immunohistochemical staining for chemokines was localized to RSV-infected ciliated cells. The authors conclude that, in differentiated human airway epithelium in vitro, RSV-induced increases in IL-8 and RANTES release are predominantly in the basolateral direction. In epithelial layers, virus-containing cells are the predominant source of the increased chemokine release. The authors speculate that similar processes in vivo influence recruitment of leukocytes to sites of RSV infection.
Mitochondrial Reactive Oxygen Species Regulate Spatial Profile of Proinflammatory Responses in Lung Venular Capillaries1

Cytokine-induced lung expression of the endothelial cell (EC) leukocyte receptor P-selectin initiates leukocyte rolling. To understand the early EC signaling that induces the expression, we conducted real-time digital imaging studies in lung venular capillaries. To compare receptor- vs nonreceptor-mediated effects, we infused capillaries with respectively, TNF-α and arachidonate. At concentrations adjusted to give equipotent increases in the cytosolic Ca2+, both agents increased reactive oxygen species (ROS) production and EC P-selectin expression. Blocking the cytosolic Ca2+ increases abolished ROS production; blocking ROS production abrogated P-selectin expression. TNF-α, but not arachidonate, released Ca2+ from endoplasmic stores and increased mitochondrial Ca2+. Furthermore, Ca2+ depletion abrogated TNF-α responses partially, but arachidonate responses completely. These differences in Ca2+ mobilization by TNF-α and arachidonate were reflected in spatial patterning in the capillary in that the TNF-α effects were localized at branch points, while the arachidonate effects were nonlocalized and extensive. Furthermore, mitochondrial blockers inhibited the TNF-α- but not the arachidonate-induced responses. These findings indicate that the different modes of Ca2+ mobilization determined the spatial patterning of the proinflammatory response in lung capillaries. Responses to TNF-α revealed that EC mitochondria regulate the proinflammatory process by generating ROS that activate P-selectin expression.
Predictors of Gastric Myoelectrical Activity in Type 2 Diabetes Mellitus

Background Previous studies have clearly demonstrated the delayed gastric emptying of solid meals in diabetics, whereas their gastric myoelectrical activity, which primarily determines gastric motility, has not yet been fully confirmed. Goals This study aimed to clarify the characteristics and potential predictors of gastric myoelectrical activity in type 2 diabetics. Study Twenty-eight diabetics and 18 healthy controls participated. Duodenal biopsy sample was used for reverse transcription-polymerase chain reaction to evaluate cholecystokinin and motilin mRNA contents. Electrogastrography was performed before and after the test meal, and was assessed in terms of dominant frequency; dominant frequency instability coefficient; and the percentage of bradygastria, normogastria, and tachygastria. Results Over the entire recording period, dominant frequency was significantly lower, and dominant frequency instability coefficient and the percentage of bradygastria were significantly higher in diabetics than in controls. In diabetics, the multiple regression analysis demonstrated that dominant frequency instability coefficient and the percentage of tachygastria in the fasting period were dependent on fasting plasma glucose level and HbA1c, respectively. Moreover, dominant frequency over the entire period and the postprandial percentage of bradygastria were significantly associated with body mass index; the fasting percentage of bradygastria and postprandial dominant frequency instability coefficient were associated with fasting serum leptin level; the postprandial percentage of bradygastria was also associated with cholecystokinin mRNA content. Conclusions Gastric myoelectrical activity in type 2 diabetics is impaired on dominant frequency, dominant frequency instability coefficient, and the percentage of bradygastria and predicted by body mass index, fasting serum leptin level, and cholecystokinin mRNA content besides the glycemic status.
Type 2 Diabetes Patients’ Needs and Preferences for Care Concerning Sexual Problems: A Cross-Sectional Survey and Qualitative Interviews

Sexual dysfunction is highly prevalent among patients with type 2 diabetes; however, little is known regarding these patients’ needs and preferences for care for sexual problems. A cross-sectional survey and 25 semistructured interviews were therefore conducted among 40- to 75-year-old type 2 diabetes patients to explore this. We learned from the survey and interviews that most participants were unaware of the association between type 2 diabetes and sexual problems. Although certain barriers for discussing sexual problems with a care provider were identified (e.g., feelings of embarrassment), patients still reported a need for discussing their problems, because sex was viewed as an important part of their relationship. Some patients had sought help, but were dissatisfied with the offered care. Patients experienced a lack of attention and information from diabetes care providers. Improving this, together with a care provider-initiated conversation, was suggested to lower the threshold for discussion. Moreover, patients preferred a care provider with whom they have a close relationship, whereas age, gender, and medical specialty were regarded to be less important. An important recommendation was to make care for sexual problems an integral part of routine diabetes care. Future research should look into these recommendations.