bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of plasma-based or serum-based assays of D-dimer and FDP for diagnosing periprosthetic joint infection: protocol for a prospective single-centre, parallel comparative study
Authors: Xu Hong , Xie Jinwei , Zhou Jing , Wang Xing , Wang Duan , Huang Zeyu , Zhou Zongke 
Published: July 2021

IntroductionSeveral studies have evaluated the diagnostic values of D-dimer and fibrin degradation product (FDP) for detecting periprosthetic joint infection (PJI), but their conclusions have been inconsistent. More importantly, whether the diagnostic value of these two biomarkers differs depending on whether they are assayed in plasma or serum is unclear.Methods and analysisThis prospective single-centre, parallel comparative study will involve patients planning to undergo revision hip or knee arthroplasty due to an aseptic mechanical failure or PJI. After the patients provide written informed consent, their serum and plasma will be sampled and assayed for D-dimer and FDP. The diagnostic value of these two biomarkers in plasma and serum will be compared with one another and with the value of two traditional inflammatory markers (C reactive protein and erythrocyte sedimentation rate) used to diagnose PJI according to the 2013 International Consensus Meeting criteria. Diagnostic value will be assessed in terms of area under receiver operating characteristic curves, sensitivity, specificity, as well as positive and negative predictive values, all calculated based on the optimal cut-off determined from the Youden index.Ethics and disseminationThis study was approved by the Ethics Committee of our hospital (approval no. 2020-859). Written informed consent will be obtained from all patients before enrollment. Study findings will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038547), and it is ongoing.Title:
Process evaluation of an implementation strategy to support uptake of a tuberculosis treatment adherence intervention to improve TB care and outcomes in Malawi
Authors: Puchalski Ritchie Lisa M , Kip Esther C , Mundeva Hayley , van Lettow Monique , Makwakwa Austine , Straus Sharon E , Hamid Jemila S , Zwarenstein Merrick , Schull Michael J , Chan Adrienne K , Martiniuk Alexandra , van Schoor Vanessa 
Published: July 2021

ObjectiveTo assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence.DesignMixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework.SettingForty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training.ParticipantsForty-five peer-trainers (PTs), 23 patients and 20 LHWs.InterventionImplementation strategy employing peer-led educational outreach, a clinical support tool and peer support network to implement a TB treatment adherence intervention.Outcome measuresProcess data were collected from study initiation to the end-of-study PT meeting, and included: LHW and patient interviews, quarterly PT meeting notes, training logs and study team observations and meeting notes. Data sources were first analysed in isolation, followed by method, data source and analyst triangulation. Analyses were conducted independently by two study team members, and themes revised through discussion and involvement of additional study team members as needed.ResultsForty-one HCs (91%) trained at least one LHW. Of 256 LHWs eligible to participate at study start 152 (59%) completed training, with the proportion trained per HC ranging from 0% to 100% at the end of initial cascade training. Lack of training incentives was the primary barrier to implementation, with intrinsic motivation to improve knowledge and skills, and to improve patient care and outcomes the primary facilitators of participation.ConclusionWe identified important challenges to and potential facilitators of implementation, scalability and sustainability, of the TB treatment adherence intervention. Findings provide guidance to scale-up, and use of the implementation strategies employed, to address LHW training and supervision in other areas.Trial registration numberNCT02533089.
Digital acoustic surveillance for early detection of respiratory disease outbreaks in Spain: a protocol for an observational study
Authors: Gabaldon-Figueira Juan Carlos , Brew Joe , Doré Dominique Hélène , Umashankar Nita , Chaccour Juliane , Orrillo Virginia , Tsang Lai Yu , Blavia Isabel , Fernández-Montero Alejandro , Bartolomé Javier , Grandjean Lapierre Simon , Chaccour C 
Published: July 2021

IntroductionCough is a common symptom of COVID-19 and other respiratory illnesses. However, objectively measuring its frequency and evolution is hindered by the lack of reliable and scalable monitoring systems. This can be overcome by newly developed artificial intelligence models that exploit the portability of smartphones. In the context of the ongoing COVID-19 pandemic, cough detection for respiratory disease syndromic surveillance represents a simple means for early outbreak detection and disease surveillance. In this protocol, we evaluate the ability of population-based digital cough surveillance to predict the incidence of respiratory diseases at population level in Navarra, Spain, while assessing individual determinants of uptake of these platforms.Methods and analysisParticipants in the Cendea de Cizur, Zizur Mayor or attending the local University of Navarra (Pamplona) will be invited to monitor their night-time cough using the smartphone app Hyfe Cough Tracker. Detected coughs will be aggregated in time and space. Incidence of COVID-19 and other diagnosed respiratory diseases within the participants cohort, and the study area and population will be collected from local health facilities and used to carry out an autoregressive moving average analysis on those independent time series. In a mixed-methods design, we will explore barriers and facilitators of continuous digital cough monitoring by evaluating participation patterns and sociodemographic characteristics. Participants will fill an acceptability questionnaire and a subgroup will participate in focus group discussions.Ethics and disseminationEthics approval was obtained from the ethics committee of the Centre Hospitalier de l’Université de Montréal, Canada and the Medical Research Ethics Committee of Navarre, Spain. Preliminary findings will be shared with civil and health authorities and reported to individual participants. Results will be submitted for publication in peer-reviewed scientific journals and international conferences.Trial registration numberNCT04762693.
Child abuse in children living with special guardians, a service evaluation of child protection medical examinations
Authors: Garstang Joanna , Hallett Nutmeg , Cropp Gabrielle , Kenyon-Blair Davina , Morgans Clare , Taylor Julie 
Published: July 2021

ObjectiveTo determine difference in frequency of referral for child protection medical examination (CPME) in children subject to special guardianship order (SGO), subject to child protection plan (CPP) or neither.DesignService evaluation analysing data from CPME reports.SettingAcute and community healthcare providers in Birmingham UK, during 2018.PatientsAll children aged 0–18 years requiring CPME.Main outcome measuresDetails were obtained from CPME reports on: age, SGO status, CPP status, reason for CPME, injuries sustained, presence of non-accidental injury.Population data were obtained from the local children’s safeguarding board and national statistics.ResultsReports were available for 292/298 (98%) CPME, relating to 288 children. 5 children were subject to SGO, 39 were subject to CPP, none subject to both. Non-accidental injury was substantiated in 189/288 (66%). The child population was 288 000. 1665 children were subject to CPP and approximately 750 subject to SGO. The relative risk (RR) for children subject to SGO requiring a CPME compared with children not subject to SGO or CPP is 7.86, p<0.0001 with 95% CI (3.26 to 19.02). The RR for children subject to a CPP requiring CPME compared with children not subject to SGO or CPP is 27.65, p<0.0001 with 95% CI (19.78 to 38.63).ConclusionsThis is a small study and findings need interpreting cautiously. Children subject to SGO may potentially be at higher risk of abuse than the general population despite living with carers who have passed social care parenting assessments. There is no register of children subject to SGO so professionals may be unable to offer families additional support. SGO families should be offered enhanced support and monitoring routinely. Children subject to CPP are not being adequately protected from further abuse.
Psychopathological outcomes and defence mechanisms in clinically healed adults with a paediatric cancer history: an exploratory study
Authors: Petralia Antonino , Bisso Emanuele , Concas Ilaria , Maglitto Antonino , Bucolo Nunzio , Alaimo Salvatore , Di Cataldo Andrea , Signorelli Maria Salvina , Pulvirenti Alfredo , Aguglia Eugenio 
Published: July 2021

BackgroundThe incidence of paediatric cancers has increased in recent years; however, with advances in the treatment of paediatric cancer, almost 80% of children and adolescents who receive a diagnosis of cancer become long-term survivors. Given the high stress levels associated with cancer, it becomes important to ascertain the risk and likelihood of psychiatric disorders in adult paediatric cancer survivors.AimsThis study aims to investigate the relationship between defence styles and predisposition to psychiatric diseases in adults with a history of paediatric cancer.MethodsWe performed an explorative study on a sample of 66 clinically healed adults with a history of paediatric cancer (survivors) during follow-up visits at the University Hospital ‘Policlinico G Rodolico’ of Catania (Italy) and 98 healthy controls among medicine students. We administered the Defence Mechanism Inventory (DMI) to assess defence styles. The Symptom Checklist-90-Revised (SCL-90-R) and the Davidson Trauma Scale (DTS) were administered to assess psychopathological indices. We conducted comprehensive statistical analysis based on correlation analysis and mediation analysis to investigate the relationship between defence styles and psychopathological outcomes in survivors compared with controls.ResultsThe survivors obtained statistically significant lower values in TAO, PRO and TAS defence styles and a higher value in REV. Both groups showed non-pathlogical mean scores in DTS and SCL-90-R (with an exception of the obsessive-compulsive subscale), with lower mean values among survivors. The results of mediation analysis showed that TAS had mediation effects on interpersonal sensitivity, anxiety, PSDI, GSI and avoidance, while TAO had mediation effects on DTS total score and intrusivity. Thus, for these psychopathological indices, the effect of the oncological pathology was indirect and mediated by TAO or TAS. Our analysis exlcluded mediation effects between the remaining variables and defence styles.ConclusionIntegrating data from mediation and correlation analysis, we found how the decreasing of TAS utilization in survivors as the consequence of cancer history, has decreased interpersonal sensitivity, anxiety and GSI score in these subjects compared with controls. Similary, the decrease of TAO utilization played a role in lower values of DTS total score and intrusivity subscale. Unexpectedly, our analysis excluded relationships between cancer history, other defence styles and psycopathological scores as we initially assumed.
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects
Authors: Bolkier Yoav , Barel Ortal , Marek-Yagel Dina , Atias-Varon Danit , Kagan Maayan , Vardi Amir , Mishali David , Katz Uriel , Salem Yishay , Tirosh-Wagner Tal , Jacobson Jeffrey M , Raas-Rothschild Annick , Chorin Odelia , Eliyahu Aviva , Sarouf Yarden , Shlomovitz Omer , Veber Alvit , Shalva Nechama , Javasky Elisheva , Ben Moshe Yishay , Staretz-Chacham Orna , Rechavi Gideon , Mane Shrikant , Anikster Yair , Vivante Asaf , Pode-Shakked Ben 
Published: July 2021

BackgroundThe molecular basis of heterotaxy and congenital heart malformations associated with disruption of left–right asymmetry is broad and heterogenous, with over 25 genes implicated in its pathogenesis thus far.ObjectiveWe sought to elucidate the molecular basis of laterality disorders and associated congenital heart defects in a cohort of 30 unrelated probands of Arab–Muslim descent, using next-generation sequencing techniques.MethodsDetailed clinical phenotyping followed by whole-exome sequencing (WES) was pursued for each of the probands and their parents (when available). Sanger sequencing was used for segregation analysis of disease-causing mutations in the families.ResultsUsing WES, we reached a molecular diagnosis for 17 of the 30 probands (56.7%). Genes known to be associated with heterotaxy and/or primary ciliary dyskinesia, in which homozygous pathogenic or likely pathogenic variants were detected, included CFAP53 (CCDC11), CFAP298 (C21orf59), CFAP300, LRRC6, GDF1, DNAAF1, DNAH5, CCDC39, CCDC40, PKD1L1 and TTC25. Additionally, we detected a homozygous disease causing mutation in DAND5, as a novel recessive monogenic cause for heterotaxy in humans. Three additional probands were found to harbour variants of uncertain significance. These included variants in DNAH6, HYDIN, CELSR1 and CFAP46.ConclusionsOur findings contribute to the current knowledge regarding monogenic causes of heterotaxy and its associated congenital heart defects and underscore the role of next-generation sequencing techniques in the diagnostic workup of such patients, and especially among consanguineous families.
The geochemical evolution of the Logan Igneous Suite, Ontario, Canada: new insights from the Logan Basin and implications for the genesis of the Mesoproterozoic Midcontinent Rift System
Authors: Cundari Robert , Hollings Pete , Smyk Mark , Carl Christian 
Published: July 2021

Abstract
The 1.1 Ga Midcontinent Rift System (MRS) of North America comprises a series of Mesoproterozoic flood basalts and intrusive rocks emplaced in the Lake Superior region. The mafic rocks preserved on the NW flank of Lake Superior offer insights into the early development of the rift. New geochemical data collected from intrusive rocks in the Logan Basin, coupled with improved constraints on timing relationships between units, allow for a better understanding of the geochemical evolution of intrusive rocks therein. The extensive dataset suggests many previously unrecognized relationships between MRS intrusive rocks, indicating multiple, distinct mantle-source characteristics with highly variable crustal contamination histories, implying a complicated magma plumbing system. The data presented here suggest that five geochemically distinct mantle source regions were involved in the emplacement of the Logan Igneous Suite, each with its own distinct contamination history and perhaps different degrees of partial melting. The geochemical variations could suggest either a progressive, relative depletion in the mantle source over time or heterogeneity of the source region. However, based on the model for MRS magmatism presented here, we suggest that units related to the Logan Igneous Suite were tapping a heterogeneous mantle source that varied over time.
High Level of Multidrug-Resistant Gram-Negative Pathogens Causing Burn Wound Infections in Hospitalized Children in Dar es Salaam, Tanzania
Authors: Kabanangi Fatima , Joachim Agricola , Nkuwi Emmanuel James , Manyahi Joel , Moyo Sabrina , Majigo Mtebe 
Published: July 2021

Background. Bacterial infection remains the most common cause of morbidity and mortality in pediatric patients with burn wounds. The increase in infection and multidrug-resistant (MDR) pathogens necessitates a periodic review of antimicrobial susceptibility patterns in the burn units. The study aimed to determine the magnitude of multidrug-resistant Gram-negative (MDRGN) bacteria in children with burn wound infections and describe the resistance patterns in the tertiary and regional hospitals in Dar es Salaam, Tanzania. Materials and Methods. The study was a hospital-based cross-sectional study design conducted between May 2017 and February 2018. Bacterial isolates from 103 wound swabs of pediatric patients with burn wounds were identified using conventional methods and API 20E. The antimicrobial susceptibility pattern was determined by the Kirby–Bauer disc diffusion method. Data were analyzed using Statistical Package for Social Science (SPSS) version 23.0. Results. A total of 136 pathogenic Gram-negative organisms were isolated from burn wound infections in pediatric patients. The most isolated Gram-negative bacterium was Pseudomonas aeruginosa (39.0%), followed by Acinetobacter spp. (28.7%) and Klebsiella spp. (16.2%). MDRGN strains made up 80.1% of all Gram-negative isolates. All (100%) Klebsiella spp. and E. coli were MDR, while 69.2% and 79.2% of Acinetobacter spp. and P. aeruginosa, respectively, displayed MDR strains. We observed high levels of resistance to commonly prescribed antibiotics. Among P. aeruginosa isolates, highest resistance (81.8%) was seen toward meropenem and piperacillin, 79.5% of Acinetobacter spp. showed resistance to aztreonam, while 93–100% of Klebsiella spp and E. coli displayed resistance to amoxyclavulanic acid, ceftriaxone, and ceftazidime. The proportion of extended-spectrum beta-lactamase producers among Enterobacteriaceae was 78.6%. There was a significant higher rate of infection with MDRGN organisms in pediatric patients with a higher percentage of total burn surface area (TBSA) than patients with lower TBSA (

p

= 0.016). Conclusions. P. aeruginosa, Acinetobacter spp., and Klebsiella spp. are the common Gram-negative pathogens causing burn wound infections in hospitalized pediatric patients in our setting. A high proportion of these organisms were multidrug resistant. The findings appeal for regular antimicrobial resistance surveillance in burn wound infection to inform empirical therapy.
Loss-of-Function Mutations in TRAF7 and KLF4 Cooperatively Activate RAS-Like GTPase Signaling and Promote Meningioma Development
Authors: Najm Paul , Zhao Peihua , Steklov Mikhail , Sewduth Raj Nayan , Baietti Maria Francesca , Pandolfi Silvia , Criem Nathan , Lechat Benoit , Maia Teresa Mendes , Van Haver Delphi , Corthout Nikky , Eyckerman Sven , Impens Francis , Sablina Anna A. 
Published: July 2021

Abstract

Meningiomas are the most common benign brain tumors. Mutations of the E3 ubiquitin ligase TRAF7 occur in 25% of meningiomas and commonly cooccur with mutations in KLF4, yet the functional link between TRAF7 and KLF4 mutations remains unclear. By generating an in vitro meningioma model derived from primary meningeal cells, we elucidated the cooperative interactions that promote meningioma development. By integrating TRAF7-driven ubiquitinome and proteome alterations in meningeal cells and the TRAF7 interactome, we identified TRAF7 as a proteostatic regulator of RAS-related small GTPases. Meningioma-associated TRAF7 mutations disrupted either its catalytic activity or its interaction with RAS GTPases. TRAF7 loss in meningeal cells altered actin dynamics and promoted anchorage-independent growth by inducing CDC42 and RAS signaling. TRAF deficiency–driven activation of the RAS/MAPK pathway promoted KLF4-dependent transcription that led to upregulation of the tumor-suppressive Semaphorin pathway, a negative regulator of small GTPases. KLF4 loss of function disrupted this negative feedback loop and enhanced mutant TRAF7-mediated cell transformation. Overall, this study provides new mechanistic insights into meningioma development, which could lead to novel treatment strategies.

Significance:
The intricate molecular cross-talk between the ubiquitin ligase TRAF7 and the transcription factor KLF4 provides a first step toward the identification of new therapies for patients with meningioma.
The Chasm We Must Cross in Japan for Re-promotion of the HPV Vaccine
Authors: Ueda Yutaka , Katayama Kayoko , Yagi Asami , Kimura Tadashi 
Published: July 2021

Abstract
In Japan, the human papillomavirus (HPV) vaccination rate has decreased from around 70% to less than 1% due to repeated media reports of diverse symptoms after HPV vaccination, and to suspension of the governmental recommendation. The challenges for re-promotion of the vaccine will be discussed from a marketing perspective. The adopter categories by which a new product penetrates the market can be divided into five groups, including Innovators, Early adopters, Early majority, Late majority, and Laggards. The 16.0% line, which is the sum of the percentages of the innovators and the early adopters, is thought to be an important determinate of whether a new product will penetrate the market. By various initiatives, vaccination coverage has recently risen to about 10%; however, there is still a large chasm difficult to cross before reaching the majority of individuals. To cross that chasm, peer education will be essential. First, community health workers will need to be educated so that they have a firm understanding of HPV vaccine and can confidently recommend vaccination to the targeted population. That population will be expected to pass on that recommendation to their acquaintances, resulting in widening dissemination of HPV vaccine among the majority.
Abstract 132: Glomerular Podocyte Damage is Mitigated by Normal HDL and ApoA1
Authors: Tsuchida Yohei , Zhong Jianyong , Anantharamaiah G.M. , Linton MacRae , Yang Haichun , Kon Valentina 
Published: July 2021

We and others have shown that chronic kidney disease (CKD) disrupts the normally beneficial effects of apoAI/HDL on many different cell types. Proteinuria which characterizes CKD is a hallmark of glomerular podocyte injury and a powerful risk factor for cardiovascular disease (CVD). Although the glomerular filtration barrier normally limits direct contact of lipoproteins with podocytes, disruption in the filtration barrier promotes such interactions. We therefore investigated the effects of normal HDL and ApoAI on injured podocytes and compared these effects to HDL isolated from subjects with CKD.
Primary podocytes were isolated from wild type mice. The cells were exposed to puromycin (PAN, 100ug/ml) with and without HDL isolated from controls with normal kidney function, individuals with CKD, normal ApoA1 (EMD Millipore Company), and ApoA-I mimetic peptide L-4F. We assessed podocyte viability and proliferation (colorimetrically), cellular production of superoxide (ROS)(HPLC), membrane lipid rafts, phosphorylated caveolin-1 (Cav-1)(western blot).

PAN significantly altered ROS production, cell viability, proliferation. ApoA1 or HDL
Cont
, but not HDL
CKD
, significantly improved each of these responses. In addition, L-4F increased podocyte viability (0.60±0.04 PAN vs 0.65±0.04 PAN+L-4F) and HDL
Cont
, but not HDL
CKD
, normalized the significant increase in PAN-induced Cav-1 phosphorylation (0.65±0.04 vs 0.81±0.05 vs 0.70±0.09, respectively).

We conclude that podocyte damage including ROS production, cellular membrane and functions can be mitigated by normal HDL or its primary lipoprotein, ApoA1, findings that parallel beneficial functions of HDL/ApoA1 on other cell types. By contrast, HDL of subjects with CKD do not provide similar benefit.