bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR Promotes Antiviral Humoral Immunity by Differentially Regulating CD4 Helper T Cell and B Cell Responses
Authors: Ye Lilin , Lee Junghwa , Xu Lifan , Mohammed Ata-Ur-Rasheed , Li Weiyan , Hale J. Scott , Tan Wendy G. , Wu Tuoqi , Davis Carl W. , Ahmed Rafi , Araki Koichi 
Published: January 2017

ABSTRACT
mTOR has important roles in regulation of both innate and adaptive immunity, but whether and how mTOR modulates humoral immune responses have yet to be fully understood. To address this issue, we examined the effects of rapamycin, a specific inhibitor of mTOR, on B cell and CD4 T cell responses during acute infection with lymphocytic choriomeningitis virus. Rapamycin treatment resulted in suppression of virus-specific B cell responses by inhibiting proliferation of germinal center (GC) B cells. In contrast, the number of memory CD4 T cells was increased in rapamycin-treated mice. However, the drug treatment caused a striking bias of CD4 T cell differentiation into Th1 cells and substantially impaired formation of follicular helper T (Tfh) cells, which are essential for humoral immunity. Further experiments in which mTOR signaling was modulated by RNA interference (RNAi) revealed that B cells were the primary target cells of rapamycin for the impaired humoral immunity and that reduced Tfh formation in rapamycin-treated mice was due to lower GC B cell responses that are essential for Tfh generation. Additionally, we found that rapamycin had minimal effects on B cell responses activated by lipopolysaccharide (LPS), which stimulates B cells in an antigen-independent manner, suggesting that rapamycin specifically inhibits B cell responses induced by B cell receptor stimulation with antigen. Together, these findings demonstrate that mTOR signals play an essential role in antigen-specific humoral immune responses by differentially regulating B cell and CD4 T cell responses during acute viral infection and that rapamycin treatment alters the interplay of immune cell subsets involved in antiviral humoral immunity.

IMPORTANCE
mTOR is a serine/threonine kinase involved in a variety of cellular activities. Although its specific inhibitor, rapamycin, is currently used as an immunosuppressive drug in transplant patients, it has been reported that rapamycin can also stimulate pathogen-specific cellular immunity in certain circumstances. However, whether and how mTOR regulates humoral immunity are not well understood. Here we found that rapamycin treatment predominantly inhibited GC B cell responses during viral infection and that this led to biased helper CD4 T cell differentiation as well as impaired antibody responses. These findings suggest that inhibition of B cell responses by rapamycin may play an important role in regulation of allograft-specific antibody responses to prevent organ rejection in transplant recipients. Our results also show that consideration of antibody responses is required in cases where rapamycin is used to stimulate vaccine-induced immunity.
Human Adenovirus Type 37 Uses αVβ1and α3β1Integrins for Infection of Human Corneal Cells
Authors: Storm Rickard J. , Persson B. David , Skalman Lars Nygård , Frängsmyr Lars , Lindström Mona , Rankin Greg , Lundmark Richard , Domellöf Fatima Pedrosa , Arnberg Niklas 
Published: January 2017

ABSTRACTEpidemic keratoconjunctivitis (EKC) is a severe, contagious ocular disease that affects 20 to 40 million individuals worldwide every year. EKC is mainly caused by six types of human adenovirus (HAdV): HAdV-8, -19, -37, -53, -54, and -56. Of these, HAdV-8, -19, and -37 use sialic acid-containing glycans as cellular receptors. αVβ3, αVβ5, and a few additional integrins facilitate entry and endosomal release of other HAdVs. With the exception of a few biochemical analyses indicating that HAdV-37 can interact physically with αVβ5, little is known about the integrins used by EKC-causing HAdVs. Here, we investigated the overall integrin expression on human corneal cells and found expression of α2, α3, α6, αV, β1, and β4 subunits in human cornealin situepithelium and/or in a human corneal epithelial (HCE) cell line but no or less accessible expression of α4, α5, β3, or β5. We also identified the integrins used by HAdV-37 through a series of binding and infection competition experiments and different biochemical approaches. Together, our data suggest that HAdV-37 uses αVβ1 and α3β1 integrins for infection of human corneal epithelial cells. Furthermore, to confirm the relevance of these integrins in the HAdV-37 life cycle, we developed a corneal multilayer tissue system and found that HAdV-37 infection correlated well with the patterns of αV, α3, and β1 integrin expression. These results provide further insight into the tropism and pathogenesis of EKC-causing HAdVs and may be of importance for future development of new antiviral drugs.IMPORTANCEKeratitis is a hallmark of EKC, which is caused by six HAdV types (HAdV-8, -19, -37, -53, -54, and -56). HAdV-37 and some other HAdV types interact with integrin αVβ5 in order to enter nonocular human cells. In this study, we found that αVβ5 is not expressed on human corneal epithelial cells, thus proposing other host factors mediate corneal infection. Here, we first characterized integrin expression patterns on corneal tissue and corneal cells. Among the integrins identified, competition binding and infection experiments and biochemical assays pointed out αVβ1 and α3β1 to be of importance for HAdV-37 infection of corneal tissue. In the absence of a good animal model for EKC-causing HAdVs, we also developed anin vitrosystem with multilayer HCE cells and confirmed the relevance of the suggested integrins during HAdV-37 infection.
Tuning the near-gap electronic structure of Cu2O by anion–cation co-doping for enhanced solar energy conversion
Authors: Si Yuan , Yang Hao-Ming , Wu Hong-Yu , Huang Wei-Qing , Yang Ke , Peng Ping , Huang Gui-Fang 
Published: January 2017

Doping is an effective strategy to tune the electronic properties of semiconductors, but some side effects caused by mono-doping degrade the specific performance of matrixes. As a model system to minimize photoproduced electron-hole pairs recombination by anion–cation co-doping, we investigate the electronic structures and optical properties of (Fe[Formula: see text]+[Formula: see text]N) co-doped Cu2O using the first-principles calculations. Compared to the case of mono-doping, the Fe[Formula: see text]N[Formula: see text] (a Fe (N) atom substituting a Cu (O) atom) co-doping reduces the energy cost of doping as a consequence of the charge compensation between the iron and nitrogen impurities, which eliminates the isolated levels (induced by mono-dopant) in the band gap. Interestingly, it is found that the contributions of different host atoms (Cu and O) away from anion (N) and cation (Fe) dopants to the variation of near band gap electronic structure of the co-doped Cu2O are different. Moreover, co-doping reduces the band gap and increases the visible-light absorption of Cu2O. Both band gap reduction and low recombination rate are critical elements for efficient light-to-current conversion in co-doped semiconductor photocatalysts. These findings raise the prospect of using co-doped Cu2O with specifically engineered electronic properties in a variety of solar applications.
Suspensory Versus Aperture Fixation of a Quadrupled Hamstring Tendon Autograft in Anterior Cruciate Ligament Reconstruction: A Meta-analysis
Authors: Browning William M. , Kluczynski Melissa A. , Curatolo Christian , Marzo John M. 
Published: January 2017

Background: Hamstring grafts have become a popular choice for anterior cruciate ligament (ACL) reconstruction; however, the most effective means of fixation of these soft tissue grafts is unknown. Purpose: To determine whether suspensory or aperture fixation of hamstring tendon autografts provides better stability and clinical outcomes in ACL reconstruction. Study Design: Meta-analysis. Methods: A literature search of studies reporting single-bundle ACL reconstructions using 4-stranded hamstring tendon autografts with aperture or suspensory fixation with a minimum 24-month follow-up was conducted. Stability and clinical outcomes were compared for aperture versus suspensory fixation. Knee stability was measured with the Lachman or pivot-shift test or KT-1000 arthrometer side-to-side difference (SSD), and outcomes were determined with the International Knee Documentation Committee (IKDC), Tegner, and Lysholm scores as well as graft failures. A random-effects model with a pooled estimate for the between-study variance was used to estimate proportions or means for each outcome and its corresponding 95% CI. Results: Forty-one studies were included, of which 20 utilized suspensory fixation techniques and 21 utilized aperture fixation techniques. A >3-mm SSD was seen more often in the aperture group than the suspensory group, which was statistically significant ( P < .0001), but there was no significant difference between groups for a >5-mm SSD ( P = .53). The aperture group demonstrated significantly more graft ruptures than did the suspensory group ( P = .03). There were no statistically significant differences in Lachman grade 0 ( P = .76), grade 1 ( P = .89), and grade 2 ( P = .55) or pivot-shift grade 0 ( P = .72), grade 1 ( P = .97), and grade 2 ( P = .28). There was no statistically significant difference in mean continuous IKDC ( P = .80), Tegner ( P = .34), or Lysholm ( P = .84) scores. Conclusion: This meta-analysis demonstrated improved overall arthrometric stability and fewer graft ruptures using suspensory fixation compared with aperture fixation of a quadrupled hamstring tendon autograft in ACL reconstruction. There were no differences in IKDC, Lysholm, Lachman, and pivot-shift outcomes between suspensory and aperture fixation.
Short segment myelitis as a first manifestation of neuromyelitis optica spectrum disorders
Authors: Huh So-Young , Kim Su-Hyun , Hyun Jae-Won , Jeong In Hye , Park Min Su , Lee Sang-Hyun , Kim Ho Jin 
Published: January 2017

Background: Some patients with neuromyelitis optica spectrum disorders (NMOSD) present with spinal cord lesions extending fewer than three vertebral segments (short transverse myelitis, STM), hindering an early diagnosis. Objective: We investigated the frequency and imaging characteristics of STM lesions in patients presenting with myelitis as an initial manifestation of NMOSD. Methods: Patients seen at three referral hospitals in Korea between June 2005 and March 2015 who met the following inclusion criteria were recruited for review: seropositivity for aquaporin-4 antibody, initial presentation with myelitis and spinal cord magnetic resonance imaging (MRI) performed within 1 month of initial myelitis onset. Results: Of the 76 enrolled patients, 65 (85.5%) collectively had 69 longitudinally extensive transverse myelitis lesions, while the remaining 11 (14.5%) had a total of 15 STM lesions. Of the 15 STM lesions, 5 spanned 2.5 vertebral segments, 6 were continuous over two segments, 3 showed a length of 1.5 segments and 1 was confined to a single segment. On axial imaging, all of the STM lesions involved the central grey matter. Conclusion: These MRI findings suggested that STM does not preclude the possibility of an NMOSD diagnosis.
A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems
Authors: Brodin N. Patrik , Velcich Anna , Guha Chandan , Tomé Wolfgang A. 
Published: January 2017

Background and Purpose: Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). Materials and Methods: The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. Results: A steep dose–response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. Conclusion: The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.
Experimental determination of rupture pressure and stress of adventitia of human middle cerebral arteries
Authors: Piechna Adam , Lombarski Leszek , Ciszek Bogdan , Cieslicki Krzysztof 
Published: January 2017

Background Intracranial arterial dissections might be attributed to the particular biomechanical properties of their specific layers. Also, knowledge of adventitia properties would be crucial in the context of intracranial balloon angioplasty. Aims The purpose of this work was to determine the rupture pressure of separated adventitia and compare it to intact cerebral arterial segments. Methods Brain specimens were harvested from 14 autopsy subjects (age range from 23 to 86 years). Pressure-inflation tests were conducted on proximal segments of middle cerebral arteries and separated adventitia layers from contralateral arteries to assess the rupture pressure values. Results The averaged rupture pressure of adventitia layers was 1.41 SD 0.25 atm (1072 SD 190 mmHg), whereas for intact arterial segments it was 2.32 SD 0.70 atm (1763 SD 532 mmHg) and diminished with age according to nonlinear regression trends. The difference beetween the aformentioned rupture pressures was positively correlated with rupture pressure of intact arterial segments ( R2 = 0.88; p < 0.001). Conclusions The obtained experimental results indicate a leading role of adventitia in building arterial strength under supraphysiological pressure conditions. The greater the rupture pressure of complete cerebral arteries, the smaller the contribution of adventitia in overall wall resistance.
Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe
Authors: Préterre Cécile , Godeneche Gaelle , Vandamme Xavier , Ronzière Thomas , Lamy Matthias , Breuilly Christophe , Urbanczyk Cédric , Wolff Valérie , Lebranchu Pierre , Sevin-Allouet Mathieu , Guillon Benoit 
Published: January 2017

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to “hand motion”, or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.
Survival analysis using primary care electronic health record data: A systematic review of the literature
Authors: Hodgkins Adam Jose , Bonney Andrew , Mullan Judy , Mayne Darren John , Barnett Stephen 
Published: January 2017

Purpose: An emerging body of research involves observational studies in which survival analysis is applied to data obtained from primary care electronic health records (EHRs). This systematic review of these studies examined the utility of using this approach. Method: An electronic literature search of the Scopus, PubMed, Web of Science, CINAHL, and Cochrane databases was conducted. Search terms and exclusion criteria were chosen to select studies where survival analysis was applied to the data extracted wholly from EHRs used in primary care medical practice. Results: A total of 46 studies that met the inclusion criteria for the systematic review were examined. All were published within the past decade (2005–2014) with a majority ( n = 26, 57%) being published between 2012 and 2014. Even though citation rates varied from nil to 628, over half ( n = 27, 59%) of the studies were cited 10 times or more. The median number of subjects was 18,042 with five studies including over 1,000,000 patients. Of the included studies, 35 (76%) were published in specialty journals and 11 (24%) in general medical journals. The many conditions studied largely corresponded well with conditions important to general practice. Conclusion: Survival analysis applied to primary care electronic medical data is a research approach that has been frequently used in recent times. The utility of this approach was demonstrated by the ability to produce research with large numbers of subjects, across a wide range of conditions and with the potential of a high impact. Importantly, primary care data were thus available to inform primary care practice.
Hypoglycemia and Clinical Outcomes in Hospitalized Patients With Diabetes: Does Association With Adverse Outcomes Remain When Number of Glucose Tests Performed Is Accounted For?
Authors: Jones Gregory C. , Timmons Joseph G. , Cunningham Scott G. , Cleland Stephen J. , Sainsbury Christopher A. R. 
Published: January 2017

Background: Hypoglycemia is associated with increased length of stay in hospital patients, but previous studies have not considered the confounding effect of increased hypoglycemia detection associated with increased capillary blood glucose (CBG) measurement in prolonged admissions. We aimed to determine the effect of recorded hypoglycemia on length of stay of hospital inpatients (LOS) when this mathematical association is subtracted. Methods: CBG data were analyzed for inpatients within our health board area (01/2009-01/2015). A simulated CBG data set was generated for each patient with an identical sampling frequency to the measured CBG data set. The mathematical component of increased LOS was determined using the simulated data set. Subtraction of this confounding mathematical association was used to provide measurement of the true clinical association between recorded hypoglycemia (CBG < 4 mmol [< 72mg/dl]) and LOS. Results: A total of 196 962 admissions of 52 475 individuals with known diabetes were analyzed. 68 809 admissions of 29 551 individuals had >4 CBG measurements made and were included in analysis. After subtraction of the mathematical association of increased sample number, the clinical effect of recorded hypoglycemia is reduced—but persists—compared to previous studies. 1-2 days with recorded hypoglycemia has a relatively minor effect on LOS. LOS increases rapidly if there are ≥3 days with recorded hypoglycemia, with an increase of 0.75 days LOS per additional day with hypoglycemia. Conclusions: This technique increases accuracy of economic modeling of the impact of hypoglycemia on health care systems. This could assist study of the impact of hypoglycemia on other outcomes by factoring for bias of increased sample numbers.
Engaging patients as partners in research: Factors associated with awareness, interest, and engagement as research partners
Authors: Hearld Kristine R , Hearld Larry R , Hall Allyson G 
Published: January 2017

Objectives: There is growing interest in engaging patients in healthcare research, which raises important questions about the factors that may promote such engagement. The purpose of this study was to examine the association between patient characteristics and three aspects of patient engagement in the medical research process: awareness, interest, and actual participation. Methods: Cross-sectional, bivariate analyses were employed using the 2014 Health Information National Trends Survey. Results: Analyses suggest modest levels of interest among respondents engaging as patient partners in the research process (37.7% of respondents), low level of awareness of what patient engagement in research was (15.3% of respondents), and a very low level of actual participation (2.7% of respondents). Respondents of higher socioeconomic status and with more positive patient attitudes regarding their health and healthcare were more likely to be interested in research. In comparison, relatively few patient characteristics were significantly associated with patient awareness and actual participation in research. Conclusion: Although it is promising that people are interested in being engaged in research, the results suggest that there is work to be done to raise awareness of these engagement opportunities. Likewise, the gap between awareness and participation highlights opportunities to identify why patients may be reluctant to participate even when they are aware of research opportunities.