bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicentre prospective cohort study assessing the effectiveness of budesonide MMX® (Cortiment®MMX®) for active, mild‐to‐moderate ulcerative colitis
Authors: Danese Silvio , Hart Ailsa , Dignass Axel , Fiorino Gionata , Louis Edouard , Bonovas Stefanos , D'Haens Geert , Dotan Iris , Rogler Gerhard , Paridaens Kristine , Peyrin-Biroulet Laurent 
Published: July 2019

BackgroundCortiment®MMX® (budesonide MMX®) is currently approved for the induction of remission in mild‐to‐moderate ulcerative colitis (UC) patients when 5‐ASA treatment is not sufficient. Data in real‐life settings are lacking.MethodsThis was a multicentre observational prospective cohort study conducted in Europe and Canada. Effectiveness, safety, and tolerability of Cortiment®MMX® in a real‐life setting of patients treated for mild‐to‐moderate UC was investigated. Patients were prescribed Cortiment®MMX® in accordance with the Summary of the Product Characteristics (SmPC).The primary endpoint was the clinical benefit of Cortiment® MMX® in routine practice (improvement ≥ 3 points in the clinical sub‐scores of the Ulcerative Colitis Disease Activity Index, UCDAI).ResultsData from 326 patients with mild‐to‐moderate UC were analysed for the primary endpoint. Clinical benefit was achieved in 60.1% (196/326) of patients at the end of Cortiment®MMX® treatment. Clinical remission (UCDAI clinical sub‐score ≤ 1), full symptoms resolution (rectal bleeding (RB) = 0 and stool frequency (SF) = 0) and symptoms resolution (RB = 0 + SF ≤ 1) at the end of the Cortiment®MMX® treatment were achieved in 51.8%, 45.1% and 63.2% of patients, respectively. The median time to symptoms resolution was 30 days (range 29.0–36.0 days). Fifty patients (14.3%) had to discontinue Cortiment®MMX® due to adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug.ConclusionsThis was the first time that a large cohort study was conducted with Cortiment®MMX® in a real‐life setting. It demonstrated that Cortiment®MMX® is effective, safe and well tolerated in about 60% of UC patients.
The utility of preoperative and intraoperative cultures for guiding urosepsis empirical treatment
Authors: Wood Brielle , Habashy David , Mayne Darren J , Dhar Ankur , Purvis Claire , Skyring Timothy 
Published: July 2019

Objective: Endoscopic upper urinary tract instrumentation is a common urological procedure; often associated with prior ureteric stenting and postoperative urosepsis. This study aimed to explore the clinical utility of preoperative urine and intraoperative urine and ureteric stent cultures in the management of urosepsis post upper urinary tract instrumentation. Methods: Prospective study involving pre-stented patients whose upper urinary tract was instrumented at a single centre between 2017 and 2018. Five cultures were collected per patient. Patients were tracked for development of postoperative urosepsis. Results: The study included 227 patients, with a 5.7% postoperative urosepsis rate. Risk of urosepsis was significantly associated with female gender, steroid use and having a colonized preoperative urine culture, intraoperative bladder urine or stent-end culture, or kidney urine culture. Patients with a colonized intraoperative bladder urine were 11 times more likely to develop urosepsis and were colonized with the same organism isolated from urosepsis cultures for 50% of cases. Conclusions: To our knowledge this is the largest cohort study which analyses five different urinary tract cultures and the relationship with postoperative urosepsis. A positive intraoperative bladder urine culture is an independent predictor of postoperative urosepsis development and causative organism, which could guide antibiotic management for these patients. Level of Evidence 3-b
Assessment of TCR signal strength of antigen-specific memory CD8+ T cells in human blood
Authors: Wu Hanchih , Witzl Ashley , Ueno Hideki 
Published: July 2019

Abstract
Assessment of the quality and the breadth of antigen (Ag)-specific memory T cells in human samples is of paramount importance to elucidate the pathogenesis and to develop new treatments in various diseases. T-cell receptor (TCR) signal strength, primarily controlled by TCR affinity, affects many fundamental aspects of T-cell biology; however, no current assays for detection of Ag-specific CD8+ T cells can assess their TCR signal strength in human samples. Here, we provide evidence that interferon regulatory factor 4 (IRF4), a transcription factor rapidly upregulated in correlation with TCR signal strength, permits the assessment of the TCR signal strength of Ag-specific CD8+ T cells in human peripheral blood mononuclear cells (PBMCs). Coexpression of IRF4 and CD137 sensitively detected peptide-specific CD8+ T cells with extremely low background in PBMCs stimulated for 18 hours with MHC class I peptides. Our assay revealed that human memory CD8+ T cells with high-affinity TCRs have an intrinsic ability to highly express CD25. Furthermore, HIV-specific CD8+ T cells in chronic HIV+ subjects were found to display primarily low-affinity TCRs with low CD25 expression capacity. Impairment in the functions of HIV-specific CD8+ T cells might be associated with their suboptimal TCR signals, as well as impaired responsiveness to interleukin-2.
IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis
Authors: Birnhuber Anna , Crnkovic Slaven , Biasin Valentina , Marsh Leigh M. , Odler Balazs , Sahu-Osen Anita , Stacher-Priehse Elvira , Brcic Luka , Schneider Frank , Cikes Nada , Ghanim Bahil , Klepetko Walter , Graninger Winfried , Allanore Yannick , Eferl Robert , Olschewski Andrea , Olschewski Horst , Kwapiszewska Grazyna 
Published: July 2019

The interleukin (IL)-1 family of cytokines is strongly associated with systemic sclerosis (SSc) and pulmonary involvement, but the molecular mechanisms are poorly understood. The aim of this study was to assess the role of IL-1α and IL-1β in pulmonary vascular and interstitial remodelling in a mouse model of SSc.IL-1α and IL-1β were localised in lungs of SSc patients and in the fos-related antigen-2 (Fra-2) transgenic (TG) mouse model of SSc. Lung function, haemodynamic parameters and pulmonary inflammation were measured in Fra-2 TG mice with or without 8 weeks of treatment with the IL-1 receptor antagonist anakinra (25 mg·kg−1·day−1). Direct effects of IL-1 on pulmonary arterial smooth muscle cells (PASMCs) and parenchymal fibroblasts were investigatedin vitro.Fra-2 TG mice exhibited increased collagen deposition in the lung, restrictive lung function and enhanced muscularisation of the vasculature with concomitant pulmonary hypertension reminiscent of the changes in SSc patients. Immunoreactivity of IL-1α and IL-1β was increased in Fra-2 TG mice and in patients with SSc. IL-1 stimulation reduced collagen expression in PASMCs and parenchymal fibroblastsviadistinct signalling pathways. Blocking IL-1 signalling in Fra-2 TG worsened pulmonary fibrosis and restriction, enhanced T-helper cell type 2 (Th2) inflammation, and increased the number of pro-fibrotic, alternatively activated macrophages.Our data suggest that blocking IL-1 signalling as currently investigated in several clinical studies might aggravate pulmonary fibrosis in specific patient subsets due to Th2 skewing of immune responses and formation of alternatively activated pro-fibrogenic macrophages.
FGF signaling patterns cell fate at the interface between tendon and bone
Authors: Roberts Ryan R. , Bobzin Lauren , Teng Camilla S. , Pal Deepanwita , Tuzon Creighton T. , Schweitzer Ronen , Merrill Amy E. 
Published: July 2019

ABSTRACT
Tendon and bone are attached by a transitional connective tissue that is morphologically graded from tendinous to osseous and develops from bipotent progenitors that co-express scleraxis (Scx) and Sox9 (Scx+/Sox9+). Scx+/Sox9+ progenitors have the potential to differentiate into either tenocytes or chondrocytes, yet the developmental mechanism that spatially resolves their bipotency at the tendon-bone interface during embryogenesis remains unknown. Here, we demonstrate that development of Scx+/Sox9+ progenitors within the mammalian lower jaw requires FGF signaling. We find that loss of Fgfr2 in the mouse tendon-bone interface reduces Scx expression in Scx+/Sox9+ progenitors and induces their biased differentiation into Sox9+ chondrocytes. This expansion of Sox9+ chondrocytes, which is concomitant with decreased Notch2-Dll1 signaling, prevents formation of a mixed population of chondrocytes and tenocytes, and instead results in ectopic endochondral bone at tendon-bone attachment units. Our work shows that FGF signaling directs zonal patterning at the boundary between tendon and bone by regulating cell fate decisions through a mechanism that employs Notch signaling.
Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice
Authors: Li Hua , Li Dainan , Wang Yuzhi , Huang Zhen , Xu Jue , Yang Tianfang , Wang Linyan , Tang Qinghuang , Cai Chen-Leng , Huang Hai , Zhang Yanding , Chen YiPing 
Published: July 2019

ABSTRACT
The sinoatrial node (SAN), the primary cardiac pacemaker, consists of a head domain and a junction/tail domain that exhibit different functional properties. However, the underlying molecular mechanism defining these two pacemaker domains remains elusive. Nkx2-5 is a key transcription factor essential for the formation of the working myocardium, but it was generally thought to be detrimental to SAN development. However, Nkx2-5 is expressed in the developing SAN junction, suggesting a role for Nkx2-5 in SAN junction development and function. In this study, we present unambiguous evidence that SAN junction cells exhibit unique action potential configurations intermediate to those manifested by the SAN head and the surrounding atrial cells, suggesting a specific role for the junction cells in impulse generation and in SAN-atrial exit conduction. Single-cell RNA-seq analyses support this concept. Although Nkx2-5 inactivation in the SAN junction did not cause a malformed SAN at birth, the mutant mice manifested sinus node dysfunction. Thus, Nkx2-5 defines a population of pacemaker cells in the transitional zone. Despite Nkx2-5 being dispensable for SAN morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker.
Zombie ant death grip due to hypercontracted mandibular muscles
Authors: Mangold Colleen A. , Ishler Melissa J. , Loreto Raquel G. , Hazen Missy L. , Hughes David P. 
Published: July 2019

ABSTRACT
There are numerous examples of parasites that manipulate the behavior of the hosts that they infect. One such host–pathogen relationship occurs between the ‘zombie-ant fungus’ Ophiocordyceps unilateralis sensu lato and its carpenter ant host. Infected ants climb to elevated locations and bite onto vegetation where they remain permanently affixed well after death. The mandibular muscles, but not the brain, of infected ants are extensively colonized by the fungus. We sought to investigate the mechanisms by which O. unilateralis s.l. may be able to influence mandibular muscle contraction despite widespread muscle damage. We found that infected muscles show evidence of hypercontraction. Despite the extensive colonization, both motor neurons and neuromuscular junctions appear to be maintained. Infection results in sarcolemmal damage, but this is not specific to the death grip. We found evidence of precise penetration of muscles by fungal structures and the presence of extracellular vesicle-like particles, both of which may contribute to mandibular hypercontraction.
Endurance Exercise Attenuates Doxorubicin-induced Cardiotoxicity
Authors: LEE YOUNGIL , KWON INSU , JANG YONGCHUL , COSIO-LIMA LUDMILA , BARRINGTON PATRICIA 
Published: July 2019

ABSTRACT

Purpose
Endurance exercise (EXE) preconditioning before DOX treatment confers cardioprotection; however, whether EXE postconditioning (i.e., EXE intervention after the completion of DOX treatment) is cardioprotective remains unknown. Thus, the aim of the present study was to investigate if EXE postconditioning provides cardioprotection by testing the hypothesis that EXE-autophagy upregulation and NADPH oxidase 2 (NOX2) downregulation would be linked to cardioprotection against DOX-induced cardiotoxicity.

Methods
C57BL/6 male mice were assigned into three groups: control (CON, n = 10), doxorubicin (DOX, n = 10), and doxorubicin + endurance exercise (DOX + EXE, n = 10). Animals assigned to DOX and DOX + EXE groups were intraperitoneally injected with DOX (5 mg·kg−1 each week for 4 wk). Forty-eight hours after the last DOX treatment, the mice assigned to DOX + EXE performed EXE on a motorized treadmill at a speed of 13–15 m·min−1 for 60 min·d−1 for 4 wk.

Results
EXE prevented DOX-induced apoptosis and mitigated tissue damages. Although DOX did not modulate auto/mitophagy, EXE significantly enhanced its flux (increased LC3-II levels, reduced p62 levels, and increased autophagosomes with mitochondria) along with increased mitochondrial fission (DRP1) and reduced fusion markers (OPA1 and MFN2). Interestingly, EXE-induced autophagy against DOX occurred in the absence of alterations of autophagy inducer AMPK or autophagy inhibitor mTOR signaling. EXE prohibited DOX-induced oxidative damages by suppressing NOX2 levels but without modulating other key antioxidant enzymes including MnSOD, CuZnSOD, catalase, and GPX1/2.

Conclusion
Our data provide novel findings that EXE-induced auto/mitophagy promotion and NOX2 downregulation are linked to cardioprotection against DOX-induced cardiotoxicity. Importantly, our study shows that EXE postconditioning intervention is effective and efficacious to prevent DOX-induced cardiac injuries.
Overreaching Attenuates Training-induced Improvements in Muscle Oxidative Capacity
Authors: BELLINGER PHILLIP M. , SABAPATHY SURENDRAN , CRAVEN JONATHAN , ARNOLD BLAYNE , MINAHAN CLARE 
Published: July 2019

ABSTRACT

Introduction
The aim of this study was to determine whether muscle oxidative capacity is influenced by alterations in training volume in middle-distance runners.

Methods
Twenty-four highly trained middle-distance runners (n = 16 males; V˙O2peak = 73.3(4.3) mL·kg−1·min−1; n = 8 females, V˙O2peak = 63.2(3.4) mL·kg−1·min−1) completed 3 wk of normal training (NormTr), 3 wk of high-volume training (HVTr; a 10%, 20%, and 30% increase in training volume during each successive week from NormTr), and a 1-wk taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before and immediately after each training period, the rate of recovery of muscle oxygen consumption (mV˙O2) of the gastrocnemius medialis was measured using near-infrared spectroscopy, with the rate constant indicating muscle oxidative capacity. Time to exhaustion (TTE) and V˙O2peak were determined during a maximal incremental treadmill test.

Results
Twelve subjects were classified as being functionally overreached (FOR) after HVTr (decreased running TTE and high perceived fatigue), whereas the other 12 subjects were classified as acutely fatigued (AF; no decrease in running TTE). The AF group demonstrated a significant increase in muscle oxidative capacity after HVTr (rate constant: 15.1% ± 9.7% min−1; P = 0.009), with no further improvement after TapTr, whereas there was no change in muscle oxidative capacity for FOR at any time point (P > 0.05). Compared with the FOR group, the AF group had substantially larger improvements in TTE from pre-HVTr to post-TapTr (FOR, 8.8% ± 3.7%; AF, 3.2% ± 3.0%; P = 0.04).

Conclusion
The present study was able to demonstrate that muscle oxidative capacity was increased in response to a period of HVTr, but only in runners who did not develop FOR. Furthermore, runners who did not develop FOR had substantially larger performance improvements after a taper period.
Erlang-S: A Data-Based Model of Servers in Queueing Networks
Authors: Azriel David , Feigin Paul D. , Mandelbaum Avishai 
Published: July 2019

Classical queueing theory has typically focused on customers, and server availability has been taken for granted. However, data accessibility and the emergence of complex service systems, for example, call centers, revealed the need to stochastically model the complex behavior of servers. In this work, we propose a new model that accommodates such behavior; we call it Erlang-S, where “S” stands for servers. Our model assumes a pool of present servers, some of whom are available to serve customers from the queue while others are not, and the process of becoming available or unavailable is modeled explicitly. Our focus here is on applying the model to real systems, specifically call centers. Estimating the parameters of the new model from call-center data is challenging because reality is observed discretely in time as opposed to its continuous evolution. We therefore use an expectation-maximization algorithm that computes the expected number of relevant quantities given the discrete-time data. Erlang-S differs from the Erlang-A model, which has been commonly used for modeling call centers: the latter model assumes that all agents who are present are, in fact, available for service. When comparing predictions of the two models against call-center data, we find that Erlang-A generally overestimates queue length and consequently also the fraction of abandonment, and Erlang-S predicts reality more closely and usefully. Our conclusion is that it is important to model explicitly server dynamics to obtain accurate and valuable models of complex service systems. This paper was accepted by Gad Allon, stochastic models and simulation.
Sublaminar polyester band fixation construct in the treatment of neuromuscular scoliosis
Authors: Rosenfeld S. , Kenney S. , Rebich E. 
Published: July 2019

Purpose Multiple fixation techniques exist for treating progressive neuromuscular scoliosis including pedicle screws, sublaminar bands/wires, hooks or a combination of instruments. Most sublaminar band constructs are supplemented with pedicle screws, hooks and/or sublaminar wires particularly at the top of the construct. There are no studies to date that describe an all/predominant sublaminar band construct. The purpose of this study was to investigate the outcomes of a sublaminar polyester band construct to treat neuromuscular scoliosis. Methods A retrospective review was conducted of 32 cases of neuromuscular scoliosis treated with posterior spinal fusion using a sublaminar band construct between 2013 and 2016 by a single surgeon at a single centre. Preoperative, immediate postoperative and two-year follow-up radiographs and clinical records were reviewed. Sagittal, coronal and pelvic obliquity correction was measured. Blood loss, length of surgery and complications were recorded. Results In all, 29 patients were included. Mean postoperative coronal plane correction was 57% (0% to 92%) and maintained at two-year follow-up. Mean sagittal balance was 2.3 cm (-2.5 to 6.4). Mean lumbar lordosis angle decreased by 7° (44° to 37°). Mean thoracic kyphosis angle increased by 9° (23° to 32°). Mean pelvic obliquity decreased by 50% (from 15° to 7°). There were four major complications (14%) and eight minor complications (21%). Mean blood loss was 1304 cc (250 cc to 2450 cc). Conclusion Sublaminar polyester band fixation constructs provide a viable option in correction of deformity in patients with neuromuscular scoliosis with comparable outcomes with what is reported with other constructs. Level of Evidence V
The Reality of Knowledge Management in Islamic Higher Education
Authors: Munadi Muhammad , Ernawati Fetty , Hakiman Hakiman 
Published: July 2019

Knowledge Management (KM) is an approach to understand how the known processes are on created, used and shared to enhance academic productivity. This study aims to determine the system of implementation of KM in Islamic higher education, having the work unit status of non-tax state revenue (Penerimaan Negara Bukan Pajak/PNBP) and public service agency (Badan Layanan Umum/BLU) and applying remuneration. This study utilizes a qualitative method with the phenomenological approach. Data collection take through observation, in-depth interviews, document analysis, and focus group discussions. The implementation of KM is with the result of academic knowledge from research products and research schemes of educational staffs, saving knowledge storage on the database through electronic and printed forms, and the knowledge taking a distribution on through printed and electronic forms which are referencing lecture notes and oral sources such as scientific consortium and lecturing. The successful implementation of KM requires supported from stakeholder policies in educational institutions. The research findings present an overview of the implementation design of KM that can be used as a platform by scholars and stakeholders in educational institutions to increase knowledge productivity.
Keywords: Knowledge Management, Production, Storage, Distribution
Abstrak
Pengelolaan pengetahuan merupakan pendekatan untuk memahami bagaimana proses pengetahuan diciptakan, digunakan, dan dibagikan untuk meningkatkan produktifitas akademik. Penelitian ini bertujuan untuk mengetahui sistem implementasi manjemen pengetahuan di Perguruan Tinggi Keagamaan Islam yang berstatus satuan kerja PNBP dan BLU yang baru menerapkan remunerasi. Metode yang digunakan dalam penelitian ini adalah kualitatif dengan pendekatan fenomenologis. Pengumpulan data dilakukan melalui observasi, wawancara mendalam, analisis dokumentasi dan focused group discussion. Penelitian ini menujukkan bahwa implementasi manajemen pengetahuan meliputi: Pertama, produksi pengetahuan bersumber pada hasil penelitian tenaga pendidikan dan tenaga kependidikan dengan berbagai skema penelitian. Kedua, penyimpanan pengetahuan dalam bentuk cetak dan elektronik. Ketiga, distribusi pengetahuan melalui cetak, elektronik, referensi perkuliahan dan lisan seperti konsorsium keilmuan dan perkuliahan. Implementasi manajemen pengetahuan akan terwujud apabila didukung oleh kebijakan pemangku jabatan di lembaga pendidikan. Temuan penelitian memberikan gambaran tentang desain implementasi manajemen pengetahuan sehingga dapat dijadikan pijakan oleh para pelaku pengetahuan serta para pemangku kebijakan di lembaga pendidikan dalam rangka peningkatkan produktifitas pengetahuan.
Kata Kunci: Manajemen Pengetahuan, Produksi, Penyimpanan, Distribusi