bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing a deceased donor program in north Indian region: lessons learnt
Authors: Gupta Vivek , Chandra Abhijit , Rahul  , Singh Manmeet , Shrivastava Peeyush Kumar , Singhai Atin , Ojha Bal Krishna , Chandra Girish , Khan Mohammed Parvez , Pandey Sant , Kant Ravi 
Published: April 2016

AbstractIntroductionLiving‐related donors are the source of almost all organ transplants in India. However, these donations fall far short of current needs, and there remains a huge disparity between demand and supply of organs. In the last five yr, a consistent increase in deceased donor transplant activity has been observed in some southern Indian states. This report describes our experience of establishing a new deceased donor program in the state of Uttar Pradesh in north India.MethodsWe describe our experience on counseling families of all brain‐dead patients admitted to our center from October 2013 to September 2014 and data on retrieving and transplanting organs.ResultsA total of 99 brain‐dead patients were identified, of which 67 were medically eligible as donors. Fourteen patients developed cardiac arrest before the counseling could begin. Only eight families agreed for multi‐organ donation.ConclusionLack of consensus among the family members, mistrust of the medical system, fear of mutilation of the body, and delay in the funeral were identified as the main reasons behind negative consent. Conversely, mass media campaign, proper ICU care of brain‐dead patients, rapport with the family and streamlining all medico legal processes were associated with positive consent.
Inhibitory effects of heterotopic noxious counter‐stimulation on perception and brain activity related to Aβ‐fibre activation
Authors: Rustamov Nabi , Tessier Jessica , Provencher Benjamin , Lehmann Alexandre , Piché Mathieu 
Published: April 2016

AbstractHeterotopic noxious counter‐stimulation (HNCS) inhibits pain and pain processes through cerebral and cerebrospinal mechanisms. However, it is unclear whether HNCS inhibits non‐nociceptive processes, which needs to be clarified for a better understanding of HNCS analgesia. The aim of this study was to examine the effects of HNCS on perception and scalp somatosensory evoked potentials (SEPs). Seventeen healthy volunteers participated in two counter‐balanced sessions, including non‐nociceptive (selective Aβ‐fibre activation) or nociceptive electrical stimulation, combined with HNCS. HNCS was produced by a 20‐min cold pressor test (left hand) adjusted individually to produce moderate pain (mean ± SEM: 42.5 ± 5.3 on a 0–100 scale, where 0 is no pain and 100 the worst pain imaginable). Non‐nociceptive electrical stimulation was adjusted individually at 80% of pain threshold and produced a tactile sensation in every subject. Nociceptive electrical stimulation was adjusted individually at 120% of RIII‐reflex threshold and produced moderate pain (45.3 ± 4.5). Shock sensation was significantly decreased by HNCS compared with baseline for non‐nociceptive (P < 0.001) and nociceptive (P < 0.001) stimulation. SEP peak‐to‐peak amplitude at Cz was significantly decreased by HNCS for non‐nociceptive (P < 0.01) and nociceptive (P < 0.05) stimulation. These results indicate that perception and brain activity related to Aβ‐fibre activation are inhibited by HNCS. The mechanisms of this effect remain to be investigated to clarify whether it involves inhibition of spinal wide‐dynamic‐range neurons by diffuse noxious inhibitory controls, supraspinal processes or both.
Adenosine A1 receptor–mediated suppression of carbamazepine‐resistant seizure‐like events in human neocortical slices
Authors: Klaft Zin‐Juan , Hollnagel Jan‐Oliver , Salar Seda , Calişkan Gürsel , Schulz Steffen B. , Schneider Ulf C. , Horn Peter , Koch Arend , Holtkamp Martin , Gabriel Siegrun , Gerevich Zoltan , Heinemann Uwe 
Published: April 2016

SummaryObjectiveThe need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy (TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug‐resistant seizure‐like events (SLEs) in human temporal cortex slices.MethodsLayer V/VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K+] and 50 μm bicuculline.ResultsActivating A1 receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A1 agonist, in slices insensitive to a high dose of carbamazepine (50 μm). Also in these cases the A1 agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A1 receptors.SignificanceSelective activation of A1 receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure‐like activity is a feasible option for future studies investigating new antiepileptic drug (AED) candidates.
Refining peripheral blood smear review rules for neonatal inpatients in a South African academic laboratory
Authors: Vaughan J. , Alli N. , Mannaru K. , Sedick Q. 
Published: April 2016

SummaryIntroductionPeripheral blood smear review (PBSR) is a labour‐intensive test, and skilled morphologists are in short supply. It is therefore helpful for laboratories to establish rules for PBSR to improve laboratory efficiency. Previously published guidelines in this regard are useful, but make few recommendations specific to neonates. Neonatal blood is characterized by several peculiarities which would be considered pathological if present in adults. Consequently, smear review rules (SRR) are often triggered in neonates without significant value being added on review. This study aimed to assess and fine‐tune the SRR triggered in neonatal samples in order to improve laboratory efficiency.MethodsFull blood counts collected from 188 neonatal inpatients of the Chris Hani Baragwanath Academic Hospital in South Africa were retrospectively reviewed, the triggered rules documented, and the value added on PBSR determined.ResultsSmear review rules were triggered in 148 (78.7%) samples, with significant morphological abnormalities identified in 84 (54.4%), and a false‐positive rate of 34.0%. In patients with unhelpful review, the commonest rules triggered were the flags querying the presence of abnormal lymphocytes, blasts or nucleated red blood cells. When one or more of these flags were triggered in the absence of any other SRR, PBSR was always noncontributory. Disregarding these flags in the current cohort would reduce both the review and the false‐positive rates by >20% without increasing the false‐negative rate.ConclusionFalse‐positive smear review is common in neonates, and minor modifications to SRR can substantially reduce the smear review rate without increasing the false‐negative rate.
ADrosophilaheat shock response represents an exception rather than a rule amongst Diptera species
Authors: Zatsepina O. G. , Przhiboro A. A. , Yushenova I. A. , Shilova V. , Zelentsova E. S. , Shostak N. G. , Evgen'ev M. B. , Garbuz D. G. 
Published: April 2016

AbstractHeat shock protein 70 (Hsp70) is the major player that underlies adaptive response to hyperthermia in all organisms studied to date. We investigated patterns of Hsp70 expression in larvae of dipteran species collected from natural populations of species belonging to four families from different evolutionary lineages of the order Diptera: Stratiomyidae, Tabanidae, Chironomidae and Ceratopogonidae. All investigated species showed a Hsp70 expression pattern that was different from the pattern inDrosophila. In contrast toDrosophila, all of the species in the families studied were characterized by high constitutive levels of Hsp70, which was more stable than that inDrosophila. When Stratiomyidae Hsp70 proteins were expressed inDrosophilacells, they became as short‐lived as the endogenous Hsp70. Interestingly, three species of Ceratopogonidae and a cold‐water species of Chironomidae exhibited high constitutive levels ofHsp70mRNA and high basal levels of Hsp70. Furthermore, two species of Tabanidae were characterized by significant constitutive levels of Hsp70 and highly stableHsp70mRNA. In most cases, heat‐resistant species were characterized by a higher basal level of Hsp70 than more thermosensitive species. These data suggest that different trends were realized during the evolution of the molecular mechanisms underlying the regulation of the responses ofHsp70genes to temperature fluctuations in the studied families.
New oral anticoagulants: appropriateness of prescribing in real‐world setting
Authors: Pattullo C. S. , Barras M. , Tai B. , McKean M. , Donovan P. 
Published: April 2016

BackgroundThe new oral anticoagulants (NOAC) have been extensively studied in the clinical trial setting; however, concerns remain about the safety of prescribing in the elderly and patients with renal impairment.AimThe aim of this study was to assess the appropriateness of NOAC prescribing in a real‐world setting in terms of patient selection and to compare patient demographics to those included in pivotal clinical trials.MethodsOne hundred and seventy‐six patients from three tertiary university teaching hospitals were identified over 3 months in 2014.ResultsMedian age of the cohort was 74 years (interquartile range: 61–81 years), with a range of 23–96 years. Overall, 34% of the study population were prescribed a NOAC inappropriately. Of these, treatment was contraindicated in 40%, predominantly due to severe renal impairment, 22% were prescribed an excessively high dose, while 38% were under dosed. Although community‐initiated patients had poorer renal function (glomerular filtration rate 91.7 ± 55.7 vs 69.3 ± 38.9, P = 0.024), appropriateness of prescription was no different compared to hospital‐initiated patients (78% during admission cf. 61% prior, P = 0.061). Appropriate prescribing was better in patients with venous thromboembolism compared to AF (85% appropriate cf. 60%, P = 0.021).ConclusionOur findings imply that there remains considerable uncertainty about appropriate prescribing and dosing of NOAC, particularly in patients with impaired renal function. We recommend judicious prescribing and regular monitoring of renal function in patients at high risk of complications from NOAC therapy.
Microenvironmental cues for T‐cell acute lymphoblastic leukemia development
Authors: Passaro Diana , Quang Christine Tran , Ghysdael Jacques 
Published: April 2016

SummaryIntensive chemotherapy regimens have led to a substantial improvement in the cure rate of patients suffering from T‐cell acute lymphoblastic leukemia (T‐ALL). Despite this progress, about 15% and 50% of pediatric and adult cases, respectively, show resistance to treatment or relapse with dismal prognosis, calling for further therapeutic investigations. T‐ALL is an heterogeneous disease, which presents intrinsic alterations leading to aberrant expression of transcription factors normally involved in hematopoietic stem/progenitor cell development and mutations in genes implicated in the regulation of cell cycle progression, apoptosis, and T‐cell development. Gene expression profiling allowed the classification of T‐ALL into defined molecular subgroups that mostly reflects the stage of their differentiation arrest. So far this knowledge has not translated into novel, targeted therapy. Recent evidence points to the importance of extrinsic signaling cues in controlling the ability of T‐ALL to home, survive, and proliferate, thus offering the perspective of new therapeutic options. This review summarizes the present understanding of the interactions between hematopoietic cells and bone marrow/thymic niches during normal hematopoiesis, describes the main signaling pathways implicated in this dialog, and finally highlights how malignant T cells rely on specific niches to maintain their ability to sustain and propagate leukemia.
Development of T‐cell tolerance utilizes both cell‐autonomous and cooperative presentation of self‐antigen
Authors: Perry Justin S. A. , Hsieh Chyi‐Song 
Published: April 2016

SummaryThe development of T‐cell self‐tolerance in the thymus is important for establishing immune homeostasis and preventing autoimmunity. Here, we review the components of T‐cell tolerance, which includes T‐cell receptor (TCR) self‐reactivity, costimulation, cytokines, and antigen presentation by a variety of antigen‐presenting cells (APCs) subsets. We discuss the current evidence on the process of regulatory T (Treg) cell and negative selection and the importance of TCR signaling. We then examine recent evidence showing unique roles for bone marrow (BM)‐derived APCs and medullary thymic epithelial cells (mTECs) on the conventional and Treg TCR repertoire, as well as emerging data on the role of B cells in tolerance. Finally, we review the accumulating data that suggest that cooperative antigen presentation is a prominent component of T ‐ell tolerance. With the development of tools to interrogate the function of individual APC subsets in the medulla, we have gained greater understanding of the complex cellular and molecular events that determine T‐cell tolerance.
T follicular regulatory cells
Authors: Sage Peter T. , Sharpe Arlene H. 
Published: April 2016

SummaryPathogen exposure elicits production of high‐affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh‐mediated B‐cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh‐mediated B‐cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr‐cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody‐mediated diseases.
Thymus: the next (re)generation
Authors: Chaudhry Mohammed S. , Velardi Enrico , Dudakov Jarrod A. , van den Brink Marcel R. M. 
Published: April 2016

SummaryAs the primary site of T‐cell development, the thymus plays a key role in the generation of a strong yet self‐tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues. The thymus is, however, capable of regenerating, restoring its function to a degree. Potential mechanisms for this endogenous thymic regeneration include keratinocyte growth factor (KGF) signaling, and a more recently described pathway in which innate lymphoid cells produce interleukin‐22 (IL‐22) in response to loss of double positive thymocytes and upregulation of IL‐23 by dendritic cells. Endogenous repair is unable to fully restore the thymus, particularly in the aged population, and this paves the way toward the need for exogenous strategies to help regenerate or even replace thymic function. Therapies currently in clinical trials include KGF, use of the cytokines IL‐7 and IL‐22, and hormonal modulation including growth hormone administration and sex steroid inhibition. Further novel strategies are emerging in the preclinical setting, including the use of precursor T cells and thymus bioengineering. The use of such strategies offers hope that for many patients, the next regeneration of their thymus is a step closer.
Parallel and nonparallel behavioural evolution in response to parasitism and predation in Trinidadian guppies
Authors: Jacquin L. , Reader S. M. , Boniface A. , Mateluna J. , Patalas I. , Pérez‐Jvostov F. , Hendry A. P. 
Published: April 2016

AbstractNatural enemies such as predators and parasites are known to shape intraspecific variability of behaviour and personality in natural populations, yet several key questions remain: (i) What is the relative importance of predation vs. parasitism in shaping intraspecific variation of behaviour across generations? (ii) What are the contributions of genetic and plastic effects to this behavioural divergence? (iii) And to what extent are responses to predation and parasitism repeatable across independent evolutionary lineages? We addressed these questions using Trinidadian guppies (Poecilia reticulata) (i) varying in their exposure to dangerous fish predators andGyrodactylusectoparasites for (ii) both wild‐caught F0 and laboratory‐reared F2 individuals and coming from (iii) multiple independent evolutionary lineages (i.e. independent drainages). Several key findings emerged. First, a population's history of predation and parasitism influenced behavioural profiles, but to different extent depending on the behaviour considered (activity, shoaling or boldness). Second, we had evidence for some genetic effects of predation regime on behaviour, with differences in activity of F2 laboratory‐reared individuals, but not for parasitism, which had only plastic effects on the boldness of wild‐caught F0 individuals. Third, the two lineages showed a mixture of parallel and nonparallel responses to predation/parasitism, with parallel responses being stronger for predation than for parasitism and for activity and boldness than for shoaling. These findings suggest that different sets of behaviours provide different pay‐offs in alternative predation/parasitism environments and that parasitism has more transient effects in shaping intraspecific variation of behaviour than does predation.
Characterization and viral susceptibility of a brain cell line from brown‐marbled grouper Epinephelus fuscoguttatus (Forsskål) with persistent betanodavirus infection
Authors: Wen C M 
Published: April 2016

AbstractA continuous cell line designated BMGB (brown‐marbled grouper brain) was established from the brain tissues of the brown‐marbled grouper Epinephelus fuscoguttatus and characterized. BMGB cells were identified as astroglial progenitor cells because they expressed glial fibrillary acidic protein and keratin and were persistently infected by betanodavirus, as confirmed through immunocytochemistry, polymerase chain reaction and immunoblot analyses. Because few intact virions were present in the BMGB cell culture fluid, the cytopathic effect (CPE) was not observed when the culture fluid was inoculated with GBC1 cells. However, BMGB cells displayed typical CPE after infection with additional betanodavirus, megalocytivirus and chum salmon reovirus. BMGB cells showed low myxovirus resistance (Mx) protein expression, which increased following betanodavirus and reovirus infection. Because the cells contained several unusual or degraded viral proteins, the persistent infection of betanodavirus in the BMGB cells may have resulted from a mechanism that destroys the viral proteins rather than the result of Mx protein expression. Despite the persistent betanodavirus infection, BMGB cells proliferated in a manner similar to other normal tropic fish cells and supported the propagation of several piscine viruses; however, the yield was lower than that of normal cells. The BMGB cells will be useful for investigating virus and host cell interaction.
Prenatal diagnosis and physical model reconstruction of agnathia–otocephaly with limb deformities (absent ulna, fibula and digits) following maternal exposure to oxymetazoline in the first trimester
Authors: Menezes Gláucia Aparecida , Araujo Júnior Edward , Lopes Jorge , Belmonte Simone , Tonni Gabriele , Werner Heron 
Published: April 2016

AbstractAgnathia–otocephaly or agnathia‐sinotia‐microstomy syndrome is the most severe malformation affecting the first branchial arch. It is a rare congenital anomaly characterized by absence of the lower jaw and abnormal ear positioning. Prenatal diagnosis is possible on conventional 2‐D ultrasound in the second trimester. Three‐dimensional ultrasound enhances detection of abnormal facial phenotype, especially in surface rendering mode. In addition, 3‐D volume datasets are used to produce a physical model of the anomaly. We present a case of second trimester ultrasound diagnosis of agnathia–otocephaly associated with limb deformities. A physical model produced using 3‐D ultrasound volume datasets facilitated better understanding of this congenital malformation, and improvement of parental counselling and management by the multispecialist team.
Nailfold Capillaroscopy and Clinical Applications in Systemic Sclerosis
Authors: Smith Vanessa , Thevissen Kristof , Trombetta Amelia C. , Pizzorni Carmen , Ruaro Barbara , Piette Yves , Paolino Sabrina , De Keyser Filip , Sulli Alberto , Melsens Karin , Cutolo Maurizio ,   On behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases
Published: April 2016

AbstractCapillary microscopy is a safe and non‐invasive tool to evaluate the morphology of the microcirculation typically affected in SSc. Next to being paramount for the “(very) early” diagnosis of SSc eyes are also geared toward capillaroscopy with the aim to be able to use it as a biomarker, especially in the prediction of future occurrence of DU. The following review will explain what capillary microscopy is and will focus additionally on studies evaluating the association between capillaroscopy and DU.