bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential cholinergic excitation of corticopontine neurons
Authors: Baker Arielle L. , O'Toole Ryan J. , Gulledge Allan T. 
Published: January 2018

Key points
Phasic activation of M1 muscarinic receptors generates transient inhibition followed by longer lasting excitation in neocortical pyramidal neurons.
Corticopontine neurons in the mouse prefrontal cortex exhibit weaker cholinergic inhibition, but more robust and longer lasting excitation, than neighbouring callosal projection neurons.
Optogenetic release of endogenous ACh in response to single flashes of light (5 ms) preferentially enhances the excitability of corticopontine neurons for many tens of seconds.
Cholinergic excitation of corticopontine neurons involves at least three ionic mechanisms: suppression of KV7 currents, activation of the calcium‐dependent non‐specific cation conductance underlying afterdepolarizations, and activation of what appears to be a calcium‐sensitive but calcium‐permeable non‐specific cation conductance.
Preferential cholinergic excitation of prefrontal corticopontine neurons may facilitate top‐down attentional processes and behaviours.
AbstractPyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non‐overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making and behaviour. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh). To better understand how ACh regulates cortical output, in slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron subtypes, exogenous ACh generated qualitatively similar biphasic responses in which brief hyperpolarization was followed by longer lasting enhancement of excitability. However, cholinergic inhibition was more pronounced in COM neurons, while excitatory responses were larger and longer lasting in CPn neurons. Similarly, optically triggered release of endogenous ACh from cholinergic terminals preferentially and persistently (for ∼40 s) enhanced the excitability of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of CPn neurons involved at least three distinct ionic mechanisms: suppression of KV7 channels (the ‘M‐current’), activation of the calcium‐dependent non‐specific cation conductance underlying afterdepolarizations, and activation of what appears to be a calcium‐sensitive but calcium‐permeable non‐specific cation conductance. Our findings demonstrate projection‐specific selectivity in cholinergic signalling in the PFC, and suggest that transient release of ACh during behaviour will preferentially promote corticofugal output.
Experimentally Validated Computational Fluid Dynamics Model for Data Center With Active Tiles
Authors: Athavale Jayati , Joshi Yogendra , Yoda Minami 
Published: January 2018

Abstract
This paper presents an experimentally validated room-level computational fluid dynamics (CFD) model for raised-floor data center configurations employing active tiles. Active tiles are perforated floor tiles with integrated fans, which increase the local volume flow rate by redistributing the cold air supplied by the computer room air conditioning (CRAC) unit to the under-floor plenum. The numerical model of the data center room consists of one cold aisle with 12 racks arranged on both sides and three CRAC units sited around the periphery of the room. The commercial CFD software package futurefacilities6sigmadcx is used to develop the model for three configurations: (a) an aisle populated with ten (i.e., all) passive tiles; (b) a single active tile and nine passive tiles in the cold aisle; and (c) an aisle populated with all active tiles. The predictions from the CFD model are found to be in good agreement with the experimental data, with an average discrepancy between the measured and computed values for total flow rate and rack inlet temperature less than 4% and 1.7 °C, respectively. The validated models were then used to simulate steady-state and transient scenarios following cooling failure. This physics-based and experimentally validated room-level model can be used for temperature and flow distributions prediction and identifying optimal number and locations of active tiles for hot spot mitigation in data centers.
Effectiveness of interventions for reducing non-occupational sedentary behaviour in adults and older adults: a systematic review and meta-analysis
Authors: Shrestha Nipun , Grgic Jozo , Wiesner Glen , Parker Alexandra , Podnar Hrvoje , Bennie Jason A , Biddle Stuart J H , Pedisic Zeljko 
Published: January 2018

BackgroundNo systematic reviews of the effectiveness of interventions for reducing non-occupational sedentary behaviour are available. Therefore, the aim of this systematic review was to assess the effectiveness of interventions for reducing non-occupational sedentary behaviour in adults and older adults.MethodsAn electronic search of nine databases was performed. Randomised controlled trials (RCT) and cluster RCTs among adults testing the effectiveness of interventions aimed to reduce non-occupational sedentary behaviour were considered for inclusion. Two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias.ResultsNineteen studies that evaluated multicomponent lifestyle interventions, counselling or education, television (TV) control devices and workplace interventions were included. Evidence from the meta-analyses suggested that interventions can reduce leisure sitting time in adults in the medium term (−30 min/day; 95% CI −58 to –2), and TV viewing in the short term (−61 min/day; 95% CI −79 to –43) and medium term (−11 min/day; 95% CI −20 to –2). No significant pooled effects were found for transport sitting time, leisure-time computer use and longer term outcomes. No evidence was available on the effectiveness of interventions for reducing non-occupational sedentary time in older adults.ConclusionsThe findings of this systematic review suggest the interventions may be effective in reducing non-occupational sedentary behaviour in the short to medium term in adults. However, no significant effect was found on longer term outcomes. The quality of evidence was, however, low to very low. No evidence was available on the effectiveness of non-occupational interventions on reducing sedentary time in older adults. Further high-quality research with larger samples is warranted.
Thailand’s national universal developmental screening programme for young children: action research for improved follow-up
Authors: Morrison Joanna , Chunsuwan Issarapa , Bunnag Petch , Gronholm Petra C , Lockwood Estrin Georgia 
Published: January 2018

IntroductionIn low-income and middle-income countries, it is estimated that one in every three preschool-age children are failing to meet cognitive or socioemotional developmental milestones. Thailand has implemented a universal national developmental screening programme (DSPM) for young children to enable detection of developmental disorders and early intervention that can improve child health outcomes. DSPM implementation is being hampered by low attendance at follow-up appointments when children fail the initial screening.MethodsAction research, using qualitative methods was conducted with 19 caregivers, 5 health workers and 1 chief at two Health Promotion Hospitals to explore the factors affecting attendance at follow-up appointments. Transcripts and notes were analysed using descriptive content analysis. Findings were then discussed with 48 health workers, managers, researchers and policymakers.ResultsThe high workload of health workers during busy vaccination clinics, and inadequate materials prevented clear communication with caregivers about the screening, how to stimulate child development and the screening result. Caregivers, particularly grandparents, had a lack of understanding about how to stimulate child development, and did not fully understand failed screening results. Caregivers felt blamed for not stimulating their child’s development, and were either worried that their child was severely disabled, or they did not believe the screening result and therefore questioned its usefulness. This led to a lack of attendance at follow-up appointments.ConclusionTask-sharing, mobile health (mhealth), community outreach and targeted interventions for grandparent caregivers might increase awareness about child development and screening, and allow health workers more time to communicate effectively. Sharing best practices, communication training and mentoring of DSPM workers coupled with mhealth job aids could also improve caregiver attendance at follow-up. Engagement of caregivers in understanding the barriers to attendance at follow-up and engagement of stakeholders in the design and implementation of interventions is important to ensure their effectiveness.
Is there a social gradient of sarcopenia? A meta-analysis and systematic review protocol
Authors: Green Darci , Duque Gustavo , Fredman Nick , Rizvi Aoun , Brennan-Olsen Sharon Lee 
Published: January 2018

IntroductionSarcopenia (or loss of muscle mass and function) is a relatively new area within the field of musculoskeletal research and medicine. Investigating whether there is a social gradient, including occupation type and income level, of sarcopenia, as observed for other diseases, will contribute significantly to the limited evidence base for this disease. This new information may inform the prevention and management of sarcopenia and widen the evidence base to support existing and future health campaigns.Methods and analysisWe will conduct a systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to identify articles that investigate associations between social determinants of health and sarcopenia in adults aged 50 years and older. Eligibility of the selected studies will be determined by two independent reviewers. The methodological quality of eligible studies will be assessed according to predetermined criteria. Established statistical methods to identify and control for heterogeneity will be used, and where appropriate, we will conduct a meta-analysis. In the event that heterogeneity prevents numerical synthesis, a best evidence analysis will be employed. This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO).Ethics and disseminationThis systematic review will use published data, thus ethical permissions will not be required. In addition to peer-reviewed publication, our results will be presented at (inter)national conferences relevant to the field of sarcopenia, ageing and/or musculoskeletal health and disseminated both electronically and in print.PROSPERO registration numberCRD42017072253.
Is postoperative bracing after pedicle screw fixation of spine fractures necessary? Study protocol of the ORNOT study: a randomised controlled multicentre trial
Authors: Smits Arjen Johannes , Deunk Jaap , Stadhouder Agnita , Altena Mark Cornelis , Kempen Diederik Hendrik Ruth , Bloemers Frank Willem 
Published: January 2018

IntroductionThe most common surgical treatment of traumatic spine fractures is through a posterior approach using pedicle screws and rods. Postoperative treatment protocols including the use of postoperative orthoses however differ between hospitals and surgeons. A three-point hyperextension orthosis is designed to support proper posture and unload the anterior column. Some motion remains when wearing an orthosis, and its main value in postoperative treatment is therefore believed to be pain relief and patient confidence. This could consequently shorten recovery time. On the other hand, an orthosis could also lead to muscle weakness and slow down recovery. Any orthosis-related complications might also be avoided. Additionally, recent studies on conservative fracture treatment show no difference in radiological outcomes with or without an orthosis. To date, no randomised studies have been performed on the use of postoperative orthoses.Methods and analysisPatients undergoing posterior fixation with pedicle screws for a traumatic thoracolumbar fracture (T7–L4) will be included in this randomised controlled multicentre non-inferiority trial. Forty-six patients will be randomised 1:1 to one of the two parallel groups; one group will wear a postoperative orthosis for 6 weeks followed by 6 weeks of weaning and one group will not wear an orthosis. The primary outcome is pain at 6 weeks reported on the Numerical Rating Scale. Secondary outcomes consist of pain on other moments, analgesic use, complications and length of hospital stay, quality of life (EuroQuol 5 Dimensions), back pain-related function (Oswestry Disability Index) and radiological outcomes with a follow-up of 1 year. Orthosis compliance is monitored weekly in the orthosis group.Ethics and disseminationThe institutional review board (METc VUmc) approved this study on 11 October 2016 under case number 2016.389. After completion of the trial, the results will be offered to an international scientific journal for peer-reviewed publication.Trial registration numberNCT03097081and NTR6285; Pre-results.
Concealment of type 1 diabetes at work in Finland: a mixed-method study
Authors: Hakkarainen Pirjo , Munir Fehmidah , Moilanen Leena , Räsänen Kimmo , Hänninen Vilma 
Published: January 2018

ObjectivesTo explore the possible reasons for concealing type 1 diabetes (T1D) at work.MethodsThe main set of data came from a cross-sectional survey (response rate 49.3%), the participants of which were 688 wage earners with T1D. Concealment of T1D was measured by asking respondents have they ever during their working career hidden their diabetes from their (A) colleagues and (B) line manager. Furthermore, semistructured interviews (n=20) were conducted to obtain deeper understanding. Questionnaire data were analysed using logistic regression analyses and qualitative interviews with inductive thematic analysis.ResultsAbout 30% of wage earners with T1D had concealed their condition during their working career from their colleagues and almost 20% from their line manager. Individuals aged 18–44 years age were more likely to conceal their T1D from their colleagues than older workers during their working career. Not disclosing T1D to the extended family (OR 5.24 (95% CI 2.06 to 13.35)), feeling an outsider at work (OR 2.47 (95% CI 1.58 to 3.84)), being embarrassed by receiving special attention at work (OR 1.99 (95% CI 1.33 to 2.96)) and neglecting treatment at work (OR 1.59 (95% CI 1.01 to 2.48)) were all associated with concealment of T1D from colleagues. The youngest age group of 18–24 years were more likely to conceal their T1D from their line managers than the older age groups during their working career. Not disclosing T1D to the extended family (OR 4.41 (95% CI 1.72 to 11.32)), feeling like an outsider at work (OR 2.51 (1.52 to 4.14)) and being embarrassed by receiving special attention at work (OR 1.81 (95% CI 1.13 to 2.91)) were associated with concealment of T1D from line managers. From the interviews, five main themes related to concealment emerged, expressing fears related to the consequences of telling: (1) being perceived as weak, (2) job discrimination, (3) unwanted attention, (4) being seen as a person who uses their T1D for seeking advantages and (5) losing privacy.ConclusionsA considerable proportion of wage earners with T1D are concealing their diagnosis often because of feelings associated with stigma. Both overemphasis and underestimation of T1D at work by the colleagues or line manager may lead to concealing T1D and may thus be harmful to self-management of T1D. The obstacles in disclosing T1D might be diminished by giving adequate information at the workplace about the condition and its significance.
Systematic review of drowning in India: assessment of burden and risk
Authors: Lukaszyk Caroline , Ivers Rebecca Q , Jagnoor Jagnoor 
Published: January 2018

AimTo examine the burden and risk factors for fatal and non-fatal drowning in India.MethodsRelevant literature was identified through a systematic search of 19 electronic databases and 19 national and global, institutional, organisational and government sources of injury data. Search terms used pertained to drowning, injury, trauma, morbidity and mortality in India.ResultsA total of 16 research articles and five data sources were included in the review. Three national data sources provided counts of drowning deaths, reporting a range of 1348–62 569 drowning deaths per year. A further three national data sources provided information on drowning-related morbidity; however, each source presented different outcome measures making comparison difficult. Ten research studies investigated risk factors associated with drowning in India. Key risk factors reported were male gender, young age (0–5 years) and individuals residing in the North-Eastern part of the country who have high exposure to water sources within community settings.ConclusionDrowning-related morbidity and mortality have a significant impact on India, with risk factors identified for this setting similar to those within other low-income and middle-income countries. Regional data which look beyond routinely collected data are required to accurately investigate the burden and impact of drowning, to inform targeted, context-specific approaches for drowning reduction initiatives
DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing
Authors: He Wen-Bin , Tu Chao-Feng , Liu Qiang , Meng Lan-Lan , Yuan Shi-Min , Luo Ai-Xiang , He Fu-Sheng , Shen Juan , Li Wen , Du Juan , Zhong Chang-Gao , Lu Guang-Xiu , Lin Ge , Fan Li-Qing , Tan Yue-Qiu 
Published: January 2018

BackgroundThe genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown.ObjectiveTo identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family.MethodsWe performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA.ResultsWe identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I.ConclusionsTo the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
Leg stereotypy syndrome: phenomenology and prevalence
Authors: Lotia Mitesh , York Michele K , Strutt Adriana M , Jankovic Joseph 
Published: January 2018

ObjectivesTo describe the phenomenology and prevalence of leg stereotypy syndrome (LSS), characterised chiefly by repetitive, rhythmical, stereotypic leg movement, especially when sitting.MethodsWe sought to characterise LSS in two groups of subjects: (1) general population (GP) group, defined as individuals accompanying patients during their visits to Baylor College of Medicine Parkinson’s Disease Center and Movement Disorders Clinic who are not genetically related to the patients; and (2) movement disorders (MD) group, composed of consecutive patients with diagnoses of restless legs syndrome, Parkinson’s disease, Tourette syndrome and tardive dyskinesia.ResultsThere were 92 participants enrolled in this study; 7% of 57 individuals in the GP group and 17% of those in the MD group met the diagnostic criteria for LSS. The mean age of individuals with LSS was 44.5 (±11.9) years and mean age at onset of LSS was 17.5 (±5.7) years. In half of the individuals, the ‘shaking’ involved predominantly one leg. All had a positive family history of similar disorder and none had diurnal variation. The seven-item Leg Stereotypy Syndrome Questionnaire was developed as a screening tool to aid in differentiating LSS from other movement disorders.ConclusionsLSS is a common condition, occurring in up to 7% of otherwise healthy individuals, and it is even more common in patients with hyperkinetic movement disorders. Although it phenomenologically may overlap with other stereotypic disorders, we argue that it is a distinct, familial, neurological syndrome.
Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains
Authors: Keogh Michael J , Wei Wei , Aryaman Juvid , Wilson Ian , Talbot Kevin , Turner Martin R , McKenzie Chris-Anne , Troakes Claire , Attems Johannes , Smith Colin , Al Sarraj Safa , Morris Chris M , Ansorge Olaf , Pickering-Brown Stuart , Jones Nick , Ironside James W , Chinnery Patrick F 
Published: January 2018

BackgroundSeveral studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series.MethodsWe analysed 980 neuropathologically characterised human brains with Alzheimer’s disease (AD), Parkinson’s disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as ‘oligogenic’.ResultsThe majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls.ConclusionsA priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases.