bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awareness of complex regional pain syndrome among medical professionals
Authors: Al‐kindi Yahya , Abudraz Mundher , Al Balushi Abdullah , Al‐Saadi Tariq 
Published: June 2020

AbstractBackgroundComplex regional pain syndrome (CRPS) is a chronic inflammatory and neurological condition with a complex broad spectrum of symptoms and requires input from various clinical specialists such as orthopedic surgeons, anesthetists, rheumatologists, and rehabilitation physicians.AimThe aim is to study the awareness of CRPS among medical professionals (Orthopedics, Neurosurgeons, Family physicians, Internists).MethodThe study was conducted using a cross‐sectional survey. A postal questionnaire was sent online to different medical professionals. The questionnaire included two sections. The first section was about personal demographic whereas the second section was about the CRPS symptoms, diagnosis criteria, and management.ResultsThe study resulted in a total number of 97 participants that filled the questionnaire completely with the highest number working at tertiary health centers (59.8%) followed by primary health centers (30.9%) and secondary health centers students (9.3%). Seventeen percent of the participants were aware about the diagnostic criteria of this condition, while only 15.4% have applied these criteria before. Awareness of risk factors and complications were 22.7% and 23.7%; respectively. The mean of the cumulative score out of 11 awareness among our participants was 2.48 (range; 0‐10). 37 (38.1%) of the participant scores 0/11 while none of the participants were able to score 11/11. Our study identified an association between years of experience and the level of awareness with a P value of .007.ConclusionThe awareness of CRPS among medical professionals was not sufficient to met the recommendation of CRPS criteria and guideline. Physicians from different specialties need to increase their knowledge and awareness about this conditions.
Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice‐site variant in Hermansky–Pudlak Syndrome 5 gene
Authors: Mériot Marina , Hitte Christophe , Rimbault Maud , Dufaure de Citres Caroline , Gache Vincent , Abitbol Marie 
Published: June 2020

AbstractIn the feline Donskoy breed, a phenotype that breeders call "pink‐eye," with associated light‐brown skin, yellow irises and red‐eye effect, has been described. Genealogical data indicated an autosomal recessive inheritance pattern. A single candidate region was identified by genome‐wide association study and SNP‐based homozygosity mapping. Within that region, we further identified HPS5 (HPS5 Biogenesis Of Lysosomal Organelles Complex 2 Subunit 2) as a strong candidate gene, since HPS5 variants have been identified in humans and animals with Hermansky–Pudlak syndrome 5 or oculocutaneous albinism. A homozygous c.2571‐1G>A acceptor splice‐site variant located in intron 16 of HPS5 was identified in pink‐eye cats. Segregation of the variant was 100% consistent with the inheritance pattern. Genotyping of 170 cats from 19 breeds failed to identify a single carrier in non‐Donskoy cats. The c.2571‐1G>A variant leads to HPS5 exon‐16 splicing that is predicted to produce a 52 amino acids in‐frame deletion in the protein. These results support an association of the pink‐eye phenotype with the c.2571‐1G>A variant. The pink‐eye Donskoy cat extends the panel of reported HPS5 variants and offers an opportunity for in‐depth exploration of the phenotypic consequences of a new HPS5 variant.
Outcome of renal cell carcinoma in patients on dialysis compared to non‐dialysis patients
Authors: Hayami Noriko , Ubara Yoshifumi , Okaneya Toshikazu , Fujii Takeshi , Nagashima Yoji , Ohashi Kenichi 
Published: June 2020

AbstractPurposeTo investigate the impact of hemodialysis on survival in renal cell carcinoma (RCC) patients.MethodsWe studied 388 patients who underwent radical or partial nephrectomy for RCC at Toranomon Hospital from 2005 to 2013. Survival curves were drawn according to the Kaplan‐Meier method and compared with the log‐rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to assess the prognostic influence of hemodialysis on cancer‐specific survival.ResultOf the 388 patients, 66 were on hemodialysis and 322 were not on dialysis. In the hemodialysis patients, incidental diagnosis of RCC was less frequent than in the non‐dialysis patients. In addition, RCC was more likely to be multicentric (41% vs 1.2%), bilateral (14% vs 0.6%), and papillary (18% vs 7%) in hemodialysis patients. Moreover, tumors were smaller, the stage was lower, and the Fuhrman nuclear grade was higher in the patients on hemodialysis. The 5‐year cancer‐specific survival rate was 82.8% for hemodialysis patients and 93.5% for nondialysis patients. Multivariate analysis indicated that hemodialysis, stage, and Fuhrman nuclear grade were independent prognostic factors for RCC.ConclusionsThis study suggested that hemodialysis was an independent prognostic factor for cancer‐specific survival in RCC patients, along with the tumor stage and Fuhrman nuclear grade.
High‐frequency (20 MHz) high‐intensity focused ultrasound: New ablative method for color‐independent tattoo removal in 1‐3 sessions. An open‐label exploratory study
Authors: Serup Jørgen , Bove Torsten , Zawada Tomasz , Jessen Alexander , Poli Mattia 
Published: June 2020

AbstractBackgroundHigh‐intensity focused ultrasound (HIFU) operating at 20 MHz is new and potentially applicable to ablative tattoo removal. The method was documented safe and rational in preclinical testing.Materials and MethodsHigh‐intensity focused ultrasound was introduced to subjects when lasers and dermatome shaving had failed or caused side effects. Transducers with focal depths between 1.1 mm and 1.7 mm in the skin were used, and settings of 0.4‐1.2 J/shot at pulse durations of 150 ms were applied. Tattoos were covered with synergistic “shoulder‐by‐shoulder” focused ultrasound shots. Effectiveness and side effects were measured.ResultsTwenty‐two subjects with 67 tattoos were treated. 62% benefitted (19% cleared, 43% partially cleared), and 28% had minor effect. VAS pain was 5‐6 versus 7‐9 with previous lasers removal. Wound healing was longer after HIFU ablation (1‐3 months). 57% of subjects had no scar or minor visible changes of skin surface markings only, while 19% had moderate or major skin thickening. Hypertrophic scar or keloid scars were not observed.Discussion/ConclusionHigh‐intensity focused ultrasound was effective in removal of difficult tattoos of any color where Nd:YAG lasers had failed. The method only needs 1‐3 sessions. As an ablative method, the wound healing period is longer than with laser removal and needs attention. Focused ultrasound can be used as a first‐line treatment of smaller tattoos independent of color, and second line when Nd:YAG lasers have failed or caused problems. The operator shall be qualified, as with lasers.
A kinetic analysis of mouse rod and cone photoreceptor responses
Authors: Reingruber Jürgen , Ingram Norianne T. , Griffis Khris G. , Fain Gordon L. 
Published: June 2020

Key points
Most vertebrate eyes have rods for dim‐light vision and cones for brighter light and higher temporal sensitivity.
Rods evolved from cone‐like precursors through expression of different transduction genes or the same genes at different expression levels, but we do not know which molecular differences were most important.
We approached this problem by analysing rod and cone responses with the same model but with different values for model parameters. We showed that, in addition to outer‐segment volume, the most important differences between rods and cones are: (1) decreased transduction gain, reflecting smaller amplification in the G‐protein cascade; (2) a faster rate of turnover of the second messenger cGMP in darkness; and (3) an accelerated rate of decay of the effector enzyme phosphodiesterase and perhaps also of activated visual pigment.
We believe our analysis has identified the principal alterations during evolution responsible for the duplex retina.
AbstractMost vertebrates have rod and cone photoreceptors, which differ in their sensitivity and response kinetics. We know that rods evolved from cone‐like precursors through the expression of different transduction genes or the same genes at different levels, but we do not know which molecular differences were most important. We have approached this problem in mouse retina by analysing the kinetic differences between rod flash responses and recent voltage‐clamp recordings of cone flash responses, using a model incorporating the principal features of photoreceptor transduction. We apply a novel method of analysis using the log‐transform of the current, and we ask which of the model's dynamic parameters need be changed to transform the flash response of a rod into that of a cone. The most important changes are a decrease in the gain of the response, reflecting a reduction in amplification of the transduction cascade; an increase in the rate of turnover of cGMP in darkness; and an increase in the rate of decay of activated phosphodiesterase, with perhaps also an increase in the rate of decay of light‐activated visual pigment. Although we cannot exclude other differences, and in particular alterations in the Ca2+ economy of the photoreceptors, we believe that we have identified the kinetic parameters principally responsible for the differences in the flash responses of the two kinds of photoreceptors, which were likely during evolution to have resulted in the duplex retina.
Investigating the formation of the Cretaceous Western Interior Seaway using landscape evolution simulations
Authors: Chang Ching , Liu Lijun 
Published: June 2020

Abstract
Transient intraplate sedimentation like the widespread Late Cretaceous Western Interior Seaway, traditionally considered a flexural foreland basin of the Sevier orogeny, is now generally accepted to be a result of dynamic topography due to the viscous force from mantle downwelling. However, the relative contributions of flexural versus dynamic subsidence are poorly understood. Furthermore, both the detailed subsidence history and the underlying physical mechanisms remain largely unconstrained. Here, we considered both Sevier orogenic loading and three different dynamic topography models that correspond to different geodynamic configurations. We used forward landscape evolution simulations to investigate the surface manifestations of these tectonic scenarios on the regional sedimentation history. We found that surface processes alone are unable to explain Western Interior Seaway sedimentation in a purely orogenic loading system, and that sedimentation increases readily inland with the additional presence of dynamic subsidence. The findings suggest that dynamic subsidence was crucial to Western Interior Seaway formation and that the dominant control on sediment distribution in the Western Interior Seaway transitioned from flexural to dynamic subsidence during 90–84 Ma, coinciding with the proposed emplacement of the conjugate Shatsky oceanic plateau. Importantly, the sedimentation records require the underlying dynamic subsidence to have been landward migratory, which implies that the underlying mechanism was the regional-scale mantle downwelling induced by the sinking Farallon flat slab underneath the westward-moving North American plate. The simulated landscape evolution also implies that prominent regional-scale Laramide uplift in the western United States should have occurred no earlier than the latest Cretaceous.
Electronic symptom monitoring in patients with metastatic lung cancer: a feasibility study
Authors: Friis Rasmus Blechingberg , Hjollund Niels Henrik , Mejdahl Caroline Trillingsgaard , Pappot Helle , Skuladottir Halla 
Published: June 2020

ObjectivesTo design an electronic questionnaire for symptom monitoring and to evaluate the feasibility, usability and acceptability when applied to patients with metastatic lung cancer.SettingSingle-centre feasibility study.ParticipantsPatients with stage IV lung cancer in antineoplastic treatment.InterventionsThis study describes the first three phases of a complex intervention design: phase 1, development of the intervention; phase 2, feasibility testing and phase 3, evaluation of the intervention. In phase 1, items were selected for the questionnaire and adjusted following patient interviews. In phase 2, patients completed the electronic questionnaire weekly during a 3-week feasibility test. In case of symptom deterioration, a nurse was notified with the aim to contact the patient. In phase 3, patients evaluated phase 2 by paper questionnaires, and interviews were conducted with the participating nurses.Primary outcome measuresThe study outcomes: phase 1, usability and relevance; phase 2, recruitment rate, compliance and threshold functionality and phase 3, usability, acceptability and relevance.ResultsIn phase 1, a questionnaire was designed and reviewed by patients (n=8). The interviews revealed high usability and relevance of the intervention.For phases 2 and 3, 20 of 29 approached patients (69%) responded to the questionnaire on a weekly basis. Two patients did not complete any questionnaires (compliance 90%). The remaining 18 patients completed 65 of a total of 72 possible questionnaires (7 missed, 93% completed). Reported symptoms led to a phone call from a nurse in 30% of the responses.The patients reported high usability and acceptability of questionnaire and software. The substance of the telephonic conversations was relevant, and the study set-up was logistically acceptable.ConclusionsAn electronic questionnaire designed for symptom monitoring revealed high usability, acceptability and relevance in the target population. In conclusion, the study set-up was considered feasible for a randomised controlled trial.Trial registration numberNCT03529851.
Accuracy of lung ultrasonography in the hands of non-imaging specialists to diagnose and assess the severity of community-acquired pneumonia in adults: a systematic review
Authors: Strøm Julie Jepsen , Haugen Pia Sperling , Hansen Malene Plejdrup , Graumann Ole , Jensen Martin Bach B , Aakjær Andersen Camilla 
Published: June 2020

ObjectivesWe aimed to systematically review the published literature regarding adults with clinical suspicion of pneumonia that compares the accuracy of lung ultrasonography (LUS) performed by non-imaging specialists to other reference standards in diagnosing and evaluating the severity of community-acquired pneumonia. Moreover, we aimed to describe LUS training and the speciality of the physician performing LUS, time spent on the LUS procedure and potential harms to patients.Materials and methodsWe searched MEDLINE, Embase, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials up until May 2019. We included studies that used LUS to diagnose pneumonia, but also confirmed pneumonia by other means. Publications were excluded if LUS was performed by a sonographer or radiologist (imaging specialists) or performed on other indications than suspicion of pneumonia. Two review authors screened and selected articles, extracted data and assessed quality using Quality Assessment of Diagnostic Accuracy Studies 2.ResultsWe included 17 studies. The sensitivity of LUS to diagnose pneumonia ranged from 0.68 to 1.00; however, in 14 studies, sensitivity was ≥0.91. Specificities varied from 0.57 to 1.00. We found no obvious differences between studies with low and high diagnostic accuracy. The non-imaging specialists were emergency physicians, internal medicine physicians, intensivists or ‘speciality not described’. Five studies described LUS training, which varied from a 1-hour course to fully credentialed ultrasound education. In general, the methodological quality of studies was good, though, some studies had a high risk of bias.ConclusionWe found significant heterogeneity across studies. In the majority of studies, LUS in the hands of the non-imaging specialists demonstrated high sensitivities and specificities in diagnosing pneumonia. However, due to problems with methodology and heterogeneity there is a need for larger studies with uniform and clearly established criteria for diagnosis and blinding.PROSPERO registration numberProspectively registered in PROSPERO (CRD42017057804).
Compliance of smokeless tobacco supply chain actors and products with tobacco control laws in Bangladesh, India and Pakistan: protocol for a multicentre sequential mixed-methods study
Authors: Khan Zohaib , Huque Rumana , Sheikh Aziz , Readshaw Anne , Eckhardt Jappe , Jackson Cath , Kanaan Mona , Iqbal Romaina , Akhter Zohaib , Garg Suneela , Singh Mongjam Meghachandra , Ahmad Fayaz , Abdullah S M , Javaid Arshad , A Khan Javaid , Han Lu , Rahman Aziz , Siddiqi Kamran 
Published: June 2020

IntroductionSouth Asia is home to more than 300 million smokeless tobacco (ST) users. Bangladesh, India and Pakistan as signatories to the Framework Convention for Tobacco Control (FCTC) have developed policies aimed at curbing the use of tobacco. The objective of this study is to assess the compliance of ST point-of-sale (POS) vendors and the supply chain with the articles of the FCTC and specifically with national tobacco control laws. We also aim to assess disparities in compliance with tobacco control laws between ST and smoked tobacco products.Methods and analysisThe study will be carried out at two sites each in Bangladesh, India and Pakistan. We will conduct a sequential mixed-methods study with five components: (1) mapping of ST POS, (2) analyses of ST samples packaging, (3) observation, (4) survey interviews of POS and (5) in-depth interviews with wholesale dealers/suppliers/manufacturers of ST. We aim to conduct at least 300 POS survey interviews and observations, and 6–10 in-depth interviews in each of the three countries. Data collection will be done by trained data collectors. The main statistical analysis will report the frequencies and proportions of shops that comply with the FCTC and local tobacco control policies, and provide a 95% CI of these estimates. The qualitative in-depth interview data will be analysed using the framework approach. The findings will be connected, each component informing the focus and/or design of the next component.Ethics and disseminationEthical approvals for the study have been received from the Health Sciences Research Governance Committee at the University of York, UK. In-country approvals were taken from the National Bioethics Committee in Pakistan, the Bangladesh Medical Research Council and the Indian Medical Research Council. Our results will be disseminated via scientific conferences, peer-reviewed research publications and press releases.
FcγRII (CD32) modulates antibody clearance in NOD SCID mice leading to impaired antibody-mediated tumor cell deletion
Authors: Oldham Robert J , Mockridge C Ian , James Sonya , Duriez Patrick J , Chan H T Claude , Cox Kerry L , Pitic Vicentiu A , Glennie Martin J , Cragg Mark S 
Published: June 2020

BackgroundImmune compromised mice are increasingly used for the preclinical development of monoclonal antibodies (mAb). Most common are non-obese diabetic (NOD) severe combined immunodeficient (SCID) and their derivatives such as NOD SCID interleukin-2 γ-/- (NSG), which are attractive hosts for patient-derived xenografts. Despite their widespread use, the relative biological performance of mAb in these strains has not been extensively studied.MethodsClinically relevant mAb of various isotypes were administered to tumor and non-tumor-bearing SCID and NOD SCID mice and the mAb clearance monitored by ELISA. Expression analysis of surface proteins in both strains was carried out by flow cytometry and immunofluorescence microscopy. Further analysis was performed in vitro by surface plasmon resonance to assess mAb affinity for Fcγ receptors (FcγR) at pH 6 and pH 7.4. NOD SCID mice genetically deficient in different FcγR were used to delineate their involvement.ResultsHere, we show that strains on the NOD SCID background have significantly faster antibody clearance than other strains leading to reduced antitumor efficacy of clinically relevant mAb. This rapid clearance is dependent on antibody isotype, the presence of Fc glycosylation (at N297) and expression of FcγRII. Comparable effects were not seen in the parental NOD or SCID strains, demonstrating the presence of a compound defect requiring both genotypes. The absence of endogenous IgG was the key parameter transferred from the SCID as reconstituting NOD SCID or NSG mice with exogenous IgG overcame the rapid clearance and recovered antitumor efficacy. In contrast, the NOD strain was associated with reduced expression of the neonatal Fc Receptor (FcRn). We propose a novel mechanism for the rapid clearance of certain mAb isotypes in NOD SCID mouse strains, based on their interaction with FcγRII in the context of reduced FcRn.ConclusionsThis study highlights the importance of understanding the limitation of the mouse strain being used for preclinical evaluation, and demonstrates that NOD SCID strains of mice should be reconstituted with IgG prior to studies of mAb efficacy.
Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade
Authors: Correale Pierpaolo , Saladino Rita Emilena , Giannarelli Diana , Giannicola Rocco , Agostino Rita , Staropoli Nicoletta , Strangio Alessandra , Del Giudice Teresa , Nardone Valerio , Altomonte Maria , Pastina Pierpaolo , Tini Paolo , Falzea Antonia Consuelo , Imbesi Natale , Arcati Valentina , Romeo Giuseppa , Caracciolo Daniele , Luce Amalia , Caraglia Michele , Giordano Antonio , Pirtoli Luigi , Necas Alois , Amler Evzen , Barbieri Vito , Tassone Pierfrancesco , Tagliaferri Pierosandro 
Published: June 2020

BackgroundNivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.MethodsWe performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients’ outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.ResultsA poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.ConclusionsThis study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.