bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics of neuropathic pain in leprosy and associated somatosensory profiles: a deep phenotyping study in India
Authors: Haroun Omer M.O. , Vollert Jan , Lockwood Diana N. , Bennett David L.H. , Pai Vivek V. , Shetty Vanaja , Wakade Anju V. , Khodke Ashish S. , Schilder Andreas , Pfau Doreen , Enax-Krumova Elena K. , Maier Christoph , Treede Rolf-Detlef , Rice Andrew S.C. 
Published: December 2019

Abstract
This study investigated the clinical characteristics and somatosensory profiles of patients suffering from leprosy in Mumbai, India. A cross-sectional deep profiling study was conducted in 86 patients with leprosy (with and without pain) using an extensive battery of phenotyping measures including structured clinical examination, psychological state (General Health Questionnaire [GHQ-12]), and a quality-of-life condition-specific instrument (Brief Pain Inventory—short form). Quantitative sensory testing was performed according to the protocol of the German Research Network on Neuropathic Pain (DFNS) to assess the somatosensory profiles in the ulnar nerve innervation territory of all participants (dorsum of the hand). Reference data from 50 healthy Indian subjects were within the range of published DFNS values. Somatosensory profiles in leprosy patients with clinically or electroneurographically diagnosed neuropathy (with and without pain) revealed a profile of sensory loss to thermal and tactile stimuli combined with preservation of vibration and deep pressure detection. Sensory gain phenomena were not generally observed in patients with leprosy. In the group of subclinical neuropathy, a high degree of impaired thermal sensation was found, which could be clinically deployed to enhance identification of leprosy neuropathy at an early stage. Quantitative sensory testing can effectively document leprosy-associated neuropathy but does not distinguish between patients with or without pain. Patients with leprosy and neuropathic pain reported a poor quality of life and less psychological well-being compared with the pain-free patients with leprosy neuropathy.
A systematic review of western medicine's understanding of pain experience, expression, assessment, and management for Australian Aboriginal and Torres Strait Islander Peoples
Authors: Arthur Luke , Rolan Paul 
Published: December 2019

Abstract
Although pain is a near-universal experience, pain expression and beliefs are highly variable and can affect assessment and management of pain. This systematic review seeks to synthesize the research findings regarding pain management for Australian Aboriginal and Torres Strait Islander peoples addressing variation as voiced by patients, clinicians, and researchers alike. A systematic review was performed across 7 research databases for all articles related to pain within Indigenous Australian peoples. Additional literature was identified by hand-searching reference lists. Articles were restricted to literature which addressed pain within Indigenous Australians as the primary focus of the article. Thematic analysis was performed to group articles according to those which focussed on the experience, expression, assessment, or management of pain. A total of 294 articles were identified on initial search of literature, of which 20 met inclusion criteria for this study. This review captured gross heterogeneity in cohorts, research methodologies, and conditions studied, making generalized assumptions impossible and inappropriate. Studies suggest that the beliefs of both patients and practitioners are important considerations in approaching effective assessment and management of pain. Health practitioners should appreciate how our own beliefs influence the management of patients and must ensure community consultation is undertaken in order to improve pain assessment and management.
Prevalence of chronic pain in developing countries: systematic review and meta-analysis
Authors: Sá Katia Nunes , Moreira Larissa , Baptista Abrahão Fontes , Yeng Lin Tchia , Teixeira Manoel Jacobsen , Galhardoni Ricardo , de Andrade Daniel Ciampi 
Published: December 2019

Abstract
Chronic pain (CP) is prevalent worldwide. Current reports on its prevalence in developing countries are heterogeneous, and to date, there is no quantitative synthesis providing a general estimation of its magnitude in the developing world. The goal of this study was to estimate the pooled prevalence of CP in the general population in developing countries. This was a PROSPERO-registered CRD42019118680 systematic review including population-based cross-sectional studies on CP from countries with ≤0.8 human developing index. We calculated prevalence using both random effects and fixed effects. Heterogeneity was calculated by the Cochran Q test and the I2 statistic. Publication bias was evaluated by visual inspection of the Egger funnel plot, as well as by the Begg rank test and the Egger linear test. Sources of heterogeneity were also explored in subgroup analyses. Twelve studies with a total of 29,902 individuals were included in this meta-analysis, of which 7263 individuals were identified with CP. The overall pooled prevalence of CP after correction for publication bias was 18% (95% confidence interval: 10%–29%), the sample presenting significant heterogeneity (I2 = 100%, P < 0.001). Subgroup analyses demonstrated that year of publication and the adopted threshold for pain chronicity could partially explain the observed heterogeneity (P < 0.05). The proportion of individuals with CP in the general population of developing countries was 18%. However, reports of prevalence have high variability, especially related to year of publication and the threshold level adopted for pain chronicity.
An audit of paediatric pain prevalence, intensity, and treatment at a South African tertiary hospital
Authors: Velazquez Cardona Caridad , Rajah Chantal , Mzoneli Youley Nosisi , Friedrichsdorf Stefan Joerg , Campbell Fiona , Cairns Carel , Rodseth Reitze Nils 
Published: December 2019

Abstract

Introduction:
Pain in paediatric inpatients is common, underrecognised, and undertreated in resource-rich countries. Little is known about the status of paediatric pain prevention and treatment in low- and middle-income countries.

Objectives:
This audit aimed to describe the prevalence and severity of pain in paediatric patients at a tertiary hospital in South Africa.

Method:
A single-day prospective observational cross-sectional survey and medical chart review of paediatric inpatients at Grey's Hospital, Pietermaritzburg, South Africa.

Results:
Sixty-three children were included, and mean patient age was 9.7 years (SD 6.17). Most patients (87%) had pain during admission, with 29% reporting preexisting (possibly chronic) pain. At the time of the study, 25% had pain (median pain score 6/10). The worst pain reported was from needle procedures, including blood draws, injections, and venous cannulation (34%), followed by surgery (22%), acute illness/infection (18%), and other procedures (14%). Pharmacological treatments included WHO step 1 (paracetamol and ibuprofen) and step 2 (tramadol, tilidine, and morphine) analgesics. The most effective integrative interventions were distraction, swaddling, and caregiver participation. Although a pain narrative was present in the majority of charts, only 16% had documented pain intensity scores.

Conclusion:
The prevalence of pain in hospitalised children in a large South African Hospital was high and pain assessment inadequately documented. There is an urgent need for pain education and development of guidelines and protocols, to achieve better pain outcomes for children. This audit will be repeated as part of a quality-improvement initiative.
Analysis of Risk Factors Associated With Drooping Deformity After Lower Eyelid Reconstruction
Authors: Abe Yoshiro , Ishida Soushi , Mineda Kazuhide , Yamashita Yutaro , Yoshimoto Sho , Hashimoto Ichiro 
Published: December 2019

Background
Lower eyelid reconstruction is challenging because of the risk of severe postreconstruction deformities of the lower eyelid, such as drooping, entropion, and ectropion. However, the risk factors for these postreconstruction deformities are unclear. The present study aimed to quantify the drooping deformity of the lower eyelid after reconstruction using a cheek rotation flap and to identify risk factors associated with postreconstruction deformities.

Methods
Our study group included 28 patients who underwent full-thickness lower eyelid reconstruction using a cheek rotation flap for anterior lamella reconstruction. We developed the drooping index to classify postreconstruction outcomes as good (index <1.2), fair (index between 1.2 and 1.5), and poor (index >1.5). We identified risk factors for a drooping deformity using univariate analyses (Mann-Whitney U or Spearman rank correlation, depending on data distribution).

Results
Overall, the drooping index ranged between 1.0 and 2.11, with an average value of 1.3. A good outcome was obtained in 11, a fair outcome in 12, and a poor outcome in 5 patients. Clinically severe ectropion was observed in five of the 17 patients in the fair and poor outcome groups, with four of these patients requiring revision surgery. Risk factors for postreconstruction drooping deformity included medial location of the tumor, resection involving more than 50% of the horizontal width of the lower eyelid, and dissection of subcutaneous tissue of the cheek extending below the zygomatic arch.

Conclusions
A cheek rotation flap provides satisfactory outcomes for full-thickness reconstruction of the lower eyelid. Extension of dissection of subcutaneous tissue of the cheek below the zygomatic arch increases the risk of postsurgical drooping deformity. Our drooping index provides a quantitative measure of drooping deformity and is clinically useful to classify outcomes.
Comparison of Nd:YAG Laser and Combined Intense Pulsed Light and Radiofrequency in the Treatment of Hypertrophic Scars
Authors: Khedr Mohamed M. , Mahmoud Wael Hussein , Sallam Fersan A. , Elmelegy Nader 
Published: December 2019

IntroductionHypertrophic scars are fibroproliferative disorders, seen after burn, trauma, and/or surgery. We aimed to compare the clinical and histopathological results of 1064-nm Nd:YAG laser and combined intense pulsed light and radiofrequency in the treatment of hypertrophic scars.MethodsFifty patients with hypertrophic scars were included in this prospective, randomized study. Twenty-five patients were treated with Nd:YAG laser and 25 patients with combined intense pulsed light and radiofrequency (E-light). The scars were evaluated at baseline, during and at 3 months after the final treatment session using the Vancouver scar scale. Biopsy specimens from scars were obtained before, during, and 3 months after the final treatment session and were stained with hematoxylin and eosin stain, Masson's trichrome stain, and immunostaining procedures for collagen I, collagen III, and TGF-β1.ResultsSignificant improvements in the total Vancouver scar scale scores before and after the treatment in both groups (P< 0.001); however, a significant difference between both groups (P< 0.001), regarding the E-light, which showed better response than Nd:YAG laser. Hematoxylin and eosin and Masson's trichrome staining showed arrangement and thinning of collagen bundles and reduction in collagen density by in both groups, but the collagen bundles thinning and parallelism were more obvious in the E-light group. Significant decrease in the concentration of collagen I, collagen III, and TGF-β1 in the E-light group as compared with the laser group (P= 0.005,P= 0.003 andP< 0.001, respectively).ConclusionsBoth modalities were successful in the treatment of hypertrophic scars; however, a significant improvement in the clinical and histopathological findings was detected with the E-light method.
Clinical Importance and Risk Factors for Postoperative Late-Onset Pneumonia After Major Oral Cancer Surgery With Microvascular Reconstruction
Authors: Hsieh Yu-Hsuan , Kao Chia-Chen , Lin Cheng-Ta , Liu Wen-Chung , Yang Kuo-Chung , Ho Yen-Yi , Tsai Wei-Hsuan , Chen Lee-Wei 
Published: December 2019

Background
Pulmonary complications are common among patients who have undergone major oral cancer surgery with microvascular reconstruction. Current literatures focused on early-onset pneumonia in the postoperative acute stage. In contrast, we are aiming to identify the clinical importance and the risk factors associated with late-onset pneumonia in oral cancer patients after acute stage.

Methods
In total, 195 patients were included from May 2014 to December 2016 and followed up for up to 1 year after surgery. Their medical histories were reviewed to identify the risk factors of late-onset pneumonia and outcome. Primary outcome was late-onset pneumonia. Other outcome measures included early-onset pneumonia, tumor recurrence, and death within 1 year after surgery.

Results
Patients with late-onset pneumonia have demonstrated a significantly higher rate of tumor recurrence (P < 0.001) and death within 1 year (P < 0.001). Independent risk factors of late-onset pneumonia identified were age (P = 0.031), previous radiotherapy (P = 0.017), postoperative radiotherapy (P = 0.002), flap size (P = 0.001), flap type other than osteocutaneous fibula flap (P = 0.009), and tumor recurrence (P < 0.001).

Conclusions
Late-onset pneumonia can act as a warning sign for oral cancer patients who have received microsurgical reconstruction, for its high correlation with tumor recurrence and mortality rate.
Vitamin D status in chronic tic-disorder and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: A pan-European study
Authors: Bond Molly , Moll Natalie , Rosello Alicia , Bond Rod , Schnell Jaana , Burger Bianka , Hoekstra Pieter J. , Dietrich Andrea , Schrag Anette , Kocovska Eva , Martino Davide , Mueller Norbert , Schwarz Markus , Meier Ute-Christiane ,   the EMTICS collaborative group
Published: December 2019

ABSTRACTBackgroundHypovitaminosis-D has been linked to neuropsychiatric conditions, but little is known about vitamin D status in individuals with chronic tic disorders (CTD). This study sought to determine whether vitamin D levels are associated with the severity of tics and presence and severity of comorbid obsessive-compulsive disorder (OCD) and/ or attention-deficit/hyperactivity disorder (ADHD).MethodsThis is a cross-sectional sub-study of the European Multicentre Tics in Children Studies (EMTICS). Vitamin D [25(OH)D] levels (ng/ml) were obtained for 327 participants with CTD at study entry and tic severity was measured using the Yale Global Tic Severity Scale (YGTSS). An association between tic severity and presence and severity of comorbid OCD and/or ADHD symptoms was analysed using multilevel models controlling for season, site, sex, age and presence of comorbid OCD and/or ADHD.ResultsThe participants comprised 247 boys and 80 girls (4-16 years, mean [SD], 10.9 [2.72]). Hypovitaminosis-D ([25(OH)D] < 20ng/ml) was present in 33% of participants with CTD and/ or comorbid OCD and/ or ADHD. The authors found no association between 25(OH)D levels and tic severity or OCD symptom severity. However, lower 25(OH)D levels were significantly associated with increased severity of ADHD symptoms in participants with CTD (β = -0.25, s.e. = 0.08, 95% CI, -0.42 to -0.09; p < 0.01).ConclusionAdditional research is needed to confirm these findings and assess whether hypovitaminosis-D may represent an underlying biological vulnerability for comorbid ADHD symptoms in CTD as it may signpost novel strategies for prevention and treatment.
Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys
Authors: Nagai Yuji , Miyakawa Naohisa , Takuwa Hiroyuki , Hori Yukiko , Oyama Kei , Ji Bin , Takahashi Manami , Huang Xi-Ping , Slocum Samuel T. , DiBerto Jeffrey F. , Xiong Yan , Urushihata Takuya , Hirabayashi Toshiyuki , Fujimoto Atsushi , Mimura Koki , English Justin G. , Liu Jing , Inoue Ken-ichi , Kumata Katsushi , Seki Chie , Ono Maiko , Shimojo Masafumi , Zhang Ming-Rong , Tomita Yutaka , Nakahara Jin , Suhara Tetsuya , Takada Masahiko , Higuchi Makoto , Jin Jian , Roth Bryan L. , Minamimoto Takafumi 
Published: December 2019

AbstractThe chemogenetic technology Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) affords remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities, and potential off-target effects of CNO represent areas for improvement. Here we provide a new high affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg/kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg/kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents the most potent, selective, metabolically stable and fast-acting DREADD agonist reported with utility in both mice and non-human primates for a variety of applications.
Position-sensing established during compaction dictates cell fate in the mammalian embryo
Authors: Royer Christophe , Leonavicius Karolis , Kip Annemarie , Fortin Deborah , Nandi Kirtirupa , Vincent Anna , Jones Celine , Child Tim , Coward Kevin , Graham Chris , Srinivas Shankar 
Published: December 2019

SUMMARYPrecise patterning within the 3-dimensional context of tissues, organs and embryos implies that cells can sense their relative position. We still understand relatively little about how cells sense their relative position within small groups of cells. During preimplantation development, outside and inside cells rely on apicobasal polarity and the Hippo pathway to choose their fate. Despite recent findings suggesting that mechanosensing may be central to this process, the relationship between blastomere geometry (i.e. shape and position) and the Hippo pathway effector YAP remains unknown. To address this, we used a highly quantitative approach to collect and analyse information on the geometry and YAP localisation of individual blastomeres of mouse and human embryos. We find that the fraction of YAP in the nucleus responds to the proportion of exposed cell surface area rather than blastomere shape. To directly test the influence of blastomere position on YAP localisation we developed an approach using hydrogel based cylindrical cavities to alter blastomere arrangement in cultured embryos. Unbiased clustering analyses of blastomeres from such embryos reveal that the ability to respond to position emerges as early as the 8-cell stage during compaction and that altering the relative position of a blastomere within an embryo can alter its fate. Finally, we demonstrate that this response is lost upon inhibiting PKC signalling, linking it to the cell polarity. Our results pinpoint when during early embryogenesis cell specification decisions are initiated and show how blastomeres can sense their position in a polarity dependent manner to alter YAP localisation.Abstract Figure
Functional dissection of basal ganglia inhibitory input onto SNc dopaminergic neurons
Authors: Evans RC , Twedell EL , Zhu M , Ascencio J , Zhang R , Khaliq ZM 
Published: December 2019

AbstractSubstania nigra (SNc) dopaminergic neurons show a pause-rebound firing pattern in response to aversive events. Because these neurons integrate information from predominately inhibitory brain areas, it is important to determine which inputs functionally inhibit the dopamine neurons and whether this pause-rebound firing pattern can be produced by a solely inhibitory input. Here, we functionally map genetically-defined inhibitory projections from the dorsal striatum (striosome and matrix) and globus pallidus (GPe; parvalbumin and Lhx6) onto SNc neurons. We find that GPe and striosomal inputs both pause firing in SNc neurons, but rebound firing only occurs after inhibition from striosomes. Indeed, we find that striosomes are synaptically optimized to produce rebound and preferentially inhibit a subpopulation of ventral, intrinsically rebound-ready SNc dopaminergic neurons on their reticulata dendrites. Therefore, we describe a self-contained dendrite-specific striatonigral circuit that can produce pause-rebound firing in the absence of excitatory input.
High-throughput single-cell functional elucidation of neurodevelopmental disease-associated genes reveals convergent mechanisms altering neuronal differentiation
Authors: Lalli Matthew A. , Avey Denis , Dougherty Joseph D. , Milbrandt Jeffrey , Mitra Robi D. 
Published: December 2019

AbstractThe overwhelming success of exome- and genome-wide association studies in discovering thousands of disease-associated genes necessitates novel high-throughput functional genomics approaches to elucidate the mechanisms of these genes. Here, we have coupled multiplexed repression of neurodevelopmental disease-associated genes to single-cell transcriptional profiling in differentiating human neurons to rapidly assay the functions of multiple genes in a disease-relevant context, assess potentially convergent mechanisms, and prioritize genes for specific functional assays. For a set of 13 autism spectrum disorder (ASD) associated genes, we demonstrate that this approach generated important mechanistic insights, revealing two functionally convergent modules of ASD genes: one that delays neuron differentiation and one that accelerates it. Five genes that delay neuron differentiation (ADNP, ARID1B, ASH1L, CHD2, andDYRK1A) mechanistically converge, as they all dysregulate genes involved in cell-cycle control and progenitor cell proliferation. Live-cell imaging after individual ASD gene repression validated this functional module, confirming that these genes reduce neural progenitor cell proliferation and neurite growth. Finally, these functionally convergent ASD gene modules predicted shared clinical phenotypes among individuals with mutations in these genes. Altogether these results demonstrate the utility of a novel and simple approach for the rapid functional elucidation of neurodevelopmental disease-associated genes.
Monoubiquitination by the Fanconi Anemia core complex locks FANCI:FANCD2 on DNA in filamentous arrays
Authors: Tan Winnie , van Twest Sylvie , Leis Andrew , Bythell-Douglas Rohan , Murphy Vincent J. , Sharp Michael , Parker Michael W , Crismani Wayne M , Deans Andrew J. 
Published: December 2019

AbstractFANCI:FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair pathway. It has been proposed that at stalled replication forks, monoubiquitinated-FANCD2 serves to recruit DNA repair proteins that contain ubiquitin-binding motifs. Here we have reconstituted the FA pathwayin vitroto study functional consequences of FANCI:FANCD2 monoubiquitination. We report that monoubiquitination does not promote any specific exogenous protein:protein interactions, but instead stabilizes FANCI:FANCD2 heterodimers on dsDNA. This locking of FANCI:FANCD2 complex on DNA requires monoubiquitination of only the FANCD2 subunit. We further show that purified monoubiquitinated FANCI:FANCD2 forms filament-like arrays on long dsDNA using electron microscopy. Our results reveal how monoubiquitinated FANCI:FANCD2 is activated upon DNA binding and present new insights to potentially modulate monoubiquitinated FANCI:FANCD2/DNA filaments in FA cells.