bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical morbidity associated with Schistosoma haematobium infection in pre‐school age children from an endemic district in Zimbabwe
Authors: Mduluza‐Jokonya Tariro L. , Naicker Thajasvarie , Kasambala Maritha , Jokonya Luxwell , Vengesai Arthur , Midzi Herald , Choto Emilia , Musonza Kimpton , Rusankaniko Simbarashe , Sibanda Elopy , Mutapi Francisca , Mduluza Takafira 
Published: June 2020

AbstractObjectiveTo investigate Schistosoma haematobium morbidity in infected pre‐school age children and establish their disease burden.MethodologyPre‐school age children (1–5 years) who were lifelong residents of the study area and had no other infections were included in the study. Participants underwent a physical examination with clinicians blinded to their infection status. Diagnosis of S. haematobium was by urine filtration.ResultsThe prevalence of S. haematobium was 35.1% (146/416). The clinical features observed in patients with Schistosoma haematobium were as follows: wheezes (morbidity attributable factor (AF = 93.9%), haematuria (AF = 92.6%), ascites (AF = 91.5%), atopy (AF = 76.9%), inguinal lymphadenopathy (AF = 68.4%), stunting (AF = 38.2), malnutrition (MUAC)(AF = 20%) and weight for height scales (AF = 5%). Schistosoma. haematobium infected children were at greater odds ratio of presenting with inguinal lymphadenopathy (AOR)=99.2(95% CI 24.2 to 854.5), wheezes in the chest (AOR = 35.4 95% CI 15.3 to 94.2), Distended abdomen with ascites (AOR = 23.9 95% CI 11.4 to 54), haematuria (AOR = 12.6 95% CI 11.6 to 14.1), atopy history (AOR = 5.6 95% CI 1.85 to 20.2), malnutrition (AOR = 2.3 95% CI 1.4 to 3.2) and stunting (AOR = 1.9 95% CI 1.1 to2.7).ConclusionThe study is novel as it demonstrates for the first time clinical morbidity markers associated with S. haematobium infection in pre‐school age children. Furthermore the study adds scientific evidence to the call for inclusion of pre‐school age children in schistosomiasis control programmes. These morbidity markers highlight the need for early diagnosis and screening for S. haematobium in pre‐school age children.
A 24‐base pair deletion in the ABO gene causes a hereditary splice site defect: a novel mechanism underlying ABO blood group O
Authors: Matzhold Eva Maria , Drexler Camilla , Wagner Andrea , Bernecker Claudia , Pessentheiner Ariane , Bogner‐Strauß Juliane Gertrude , Helmberg Wolfgang , Wagner Thomas 
Published: June 2020

BACKGROUNDBlood group A and B antigens are synthesized by glycosyltransferases regulated by a complex molecular genetic background. A multibase deletion in the ABO gene was identified in two related blood donors. To define its hereditary character and to evaluate genotype–phenotype associations, a detailed study including 30 family members was conducted.METHODS AND MATERIALSABO phenotyping was performed with agglutination techniques and adsorption‐elution tests. The secretor status was determined. Allele‐specific sequencing of ABO and genotyping of family members by a mutation‐specific polymerase chain reaction were carried out. Functional analysis included cloning of complementary DNA and transfection experiments in HeLa cells. The antigen expression was investigated by flow cytometry and adsorption‐elution method.RESULTSSequencing analysis revealed a 24‐bp deletion in Exon 5 and the adjacent intronic region of ABO. The alteration was inherited by 16 family members. Nine of them being heterozygous for the mutated allele failed to express A antigen on their erythrocytes as found by routine typing. In particular samples, however, adsorption‐elution studies indicated inconclusive results. HeLa cells transfected with aberrant gene transcripts did not express blood group antigen A.CONCLUSIONThe variation causes defects in messenger RNA splicing, most likely inactivating the transferase as observed by serological typing and in vitro expression analysis. These data suggest a novel mechanism associated with blood group O and extend the knowledge of exceptionally rare ABO splice site mutations and deletions. With increased understanding of the molecular bases of ABO, the diagnostics may be further enhanced to ensure the safest possible use of the blood supply.
Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study
Authors: Grunwald Juan E , Pistilli Maxwell , Ying Gui-Shuang , Maguire Maureen G , Daniel Ebenezer , Whittock-Martin Revell , Parker-Ostroff Candace , Jacoby Douglas , Go Alan S , Townsend Raymond R , Gadegbeku Crystal Ann , Lash James P , Fink Jeffrey Craig , Rahman Mahboob , Feldman Harold , Kusek John W , Xie Dawei 
Published: June 2020

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.
Study protocol for an international, multicentre stepped-wedge cluster randomised trial to evaluate the impact of a digital antimicrobial stewardship smartphone application
Authors: Helou R I , Catho Gaud , Peyravi Latif Annabel , Mouton Johan , Hulscher M , Teerenstra Steven , Conly John , Huttner Benedikt D , Tängdén Thomas , Verbon Annelies 
Published: June 2020

IntroductionWith the widespread use of electronic health records and handheld electronic devices in hospitals, informatics-based antimicrobial stewardship interventions hold great promise as tools to promote appropriate antimicrobial drug prescribing. However, more research is needed to evaluate their optimal design and impact on quantity and quality of antimicrobial prescribing.Methods and analysisUse of smartphone-based digital stewardship applications (apps) with local guideline directed empirical antimicrobial use by physicians will be compared with antimicrobial prescription as per usual as primary outcome in three hospitals in the Netherlands, Sweden and Switzerland. Secondary outcomes will include antimicrobial use metrics, clinical and process outcomes. A multicentre stepped-wedge cluster randomised trial will randomise entities defined as wards or specialty regarding time of introduction of the intervention. We will include 36 hospital entities with seven measurement periods in which the primary outcome will be measured in 15 participating patients per time period per cluster. At participating wards, patients of at least 18 years of age using antimicrobials will be included. After a baseline period of 2-week measurements, six periods of 4 weeks will follow in which the intervention is introduced in 6 wards (in three hospitals) until all 36 wards have implemented the intervention. Thereafter, we allow use of the app by everyone, and evaluate the sustainability of the app use 6 months later.Ethics and disseminationThis protocol has been approved by the institutional review board of each participating centre. Results will be disseminated via media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications.Trial registration numberClinicalTrials.gov registry (NCT03793946). Stage; pre-results.
Personal-recovery-oriented community mental healthcare: qualitative evaluation of a developmental project
Authors: Beckers Thijs , Jaeqx - van Tienen Lia , Willems Rudy , Koopmans Martijn , Corstens Dirk 
Published: June 2020

ObjectivesMental healthcare is commonly aimed at reducing symptoms in individual service users. When only symptomatic recovery is addressed, not all service users experience sufficient recovery, and when care is aimed only at individuals (instead of the neighbourhood), not all people in need of mental healthcare are reached. This study evaluated a project that aimed to improve mental healthcare in a neighbourhood, by improving healthcare providers’ outreach to the residents living in the neighbourhood, by improving collaboration among healthcare providers and focussing on the residents’ personal recovery. This project was carried out by several public health services. It aimed to change the goal of mental healthcare provided in the neighbourhood from symptom reduction to personal recovery.DesignThe study included qualitative focus groups and inductive content analysis.SettingPrimary and secondary mental healthcare that healthcare workers from different healthcare services provided.ParticipantsThe evaluation was conducted through three focus group interviews with services users, their friends and relatives, neighbourhood residents, neighbourhood representatives and the healthcare services that were involved (n = 24).ResultsEvaluation indicated that the most valued part of the project was the utilisation of peer workers at the initiation of mental healthcare. Improved communication among healthcare providers that the project fostered was also highly regarded. The aim of the project to align it with existing initiatives in the neighbourhood was also considered important, although it was difficult to achieve.ConclusionsThe project did not find a panacea for recovery-oriented community mental healthcare. A variety of its components did, however, contribute to the mental health of the community residents.
Study protocol of validating a numerical model to assess the blood flow in the circle of Willis
Authors: Shen Yuanyuan , Wei Yanji , Bokkers Reinoud P H , Uyttenboogaart Maarten , van Dijk J Marc C 
Published: June 2020

IntroductionWe developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions.Methods and analysisThis study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients.Ethics and disseminationThis study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen: METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication.Trial registration numberNL8114.
Parents’ perceptions of core outcomes in neonatal research in two Nigerian neonatal units
Authors: Read Sarah Kathryn , Jibril Aisha , Tongo Olukemi , Akindolire Abimbole , Abdulkadir Isa , Nabwera Helen , Sinha Ian , Allen Stephen 
Published: June 2020

BackgroundThere is a scarcity of information regarding the most important outcomes for research in neonatal units in low-resource settings. Identification of important outcomes by different stakeholder groups would inform the development of a core outcome set (COS) for use in neonatal research.ObjectiveTo determine the perceptions and opinions of parents of newborn babies regarding what outcomes were most important to them in order to contribute towards development of a COS for neonatal research in sub-Saharan Africa.MethodsSemistructured interviews were undertaken with parents, mostly mothers, of babies admitted to one neonatal unit in North central and one in Southwest Nigeria. Participants were purposively sampled to include parents of babies with common neonatal problems such as prematurity.ResultsWe conducted 31 interviews. The most frequently raised outcomes were breast feeding, good health outcomes for their baby, education, growth and financial cost. Parents placed more emphasis on quality of life and functional status than health complications.ConclusionsThe opinions of parents need to be considered in developing a COS for neonatal research in low-resource settings. Further research should assess the opinions of families in other low-resource settings and also engage a broader range of stakeholders.
SETDB1 is required for intestinal epithelial differentiation and the prevention of
intestinal inflammation
Authors: Južnić Lea , Peuker Kenneth , Strigli Anne , Brosch Mario , Herrmann Alexander , Häsler Robert , Koch Michael , Matthiesen Liz , Zeissig Yvonne , Löscher Britt-Sabina , Nuber Alexander , Schotta Gunnar , Neumeister Volker , Chavakis Triantafyllos , Kurth Thomas , Lesche Mathias , Dahl Andreas , von Mässenhausen Anne , Linkermann Andreas , Schreiber Stefan , Aden Konrad , Rosenstiel Philip C , Franke Andre , Hampe Jochen , Zeissig Sebastian 
Published: June 2020

Objective
The intestinal epithelium is a rapidly renewing tissue which plays central roles
in nutrient uptake, barrier function and the prevention of intestinal inflammation.
Control of epithelial differentiation is essential to these processes and is dependent
on cell type-specific activity of transcription factors which bind to accessible
chromatin. Here, we studied the role of SET Domain Bifurcated Histone Lysine
Methyltransferase 1, also known as ESET (SETDB1), a histone H3K9 methyltransferase, in
intestinal epithelial homeostasis and IBD.

Design
We investigated mice with constitutive and inducible intestinal epithelial
deletion of Setdb1, studied the expression of SETDB1 in
patients with IBD and mouse models of IBD, and investigated the abundance of
SETDB1 variants in healthy individuals and patients with
IBD.

Results
Deletion of intestinal epithelial Setdb1 in mice was
associated with defects in intestinal epithelial differentiation, barrier disruption,
inflammation and mortality. Mechanistic studies showed that loss of SETDB1 leads to
de-silencing of endogenous retroviruses, DNA damage and intestinal epithelial cell
death. Predicted loss-of-function variants in human SETDB1
were considerably less frequently observed than expected, consistent with a critical
role of SETDB1 in human biology. While the vast majority of patients with IBD showed
unimpaired mucosal SETDB1 expression, comparison of IBD and non-IBD exomes revealed
over-representation of individual rare missense variants in
SETDB1 in IBD, some of which are predicted to be
associated with loss of function and may contribute to the pathogenesis of intestinal
inflammation.

Conclusion
SETDB1 plays an essential role in intestinal epithelial homeostasis. Future work
is required to investigate whether rare variants in SETDB1
contribute to the pathogenesis of IBD.
New considerations about Chiari‐like malformation, syringomyelia and their management
Authors: Rusbridge Clare 
Published: June 2020

Background: Chiari‐like malformation (CM) is a developmental condition, characterised by a conformational change and overcrowding of the brain and cranial cervical spinal cord. CM‐associated pain (CM‐P) and syringomyelia are increasingly being diagnosed, due to the rising popularity of predisposed brachycephalic breeds and the availability of MRI in veterinary practices.Aim of the article: This article aims to update the veterinary profession on these conditions, and provides a guide to diagnosis and treatment of clinically relevant disease.
Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab
Authors: Hopkins Ashley M , Kichenadasse Ganessan , Karapetis Chris S , Rowland Andrew , Sorich Michael J 
Published: June 2020

BackgroundPreliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs.MethodsThe study pooled data from patients with NSCLC in the randomized trials OAK and POPLAR (atezolizumab vs docetaxel; n=1464), and single-arm atezolizumab trials BIRCH and FIR (n=797). The association between ETS (≥10% decrease in pretreatment sum-of-longest diameters of target-lesions at 6 weeks) and overall survival (OS), progression-free survival (PFS), time to deterioration (TDD) in health-related quality-of-life (HRQoL) and physical function (PF) was assessed using Cox proportional hazard analysis.ResultsETS occurred in 20% of atezolizumab-treated patients with NSCLC within OAK and POPLAR and was associated with highly favorable OS (HR 0.33, p<0.001), PFS (HR 0.31, p<0.001), TDD in HRQoL (HR 0.73, p=0.01) and PF (HR 0.52, p<0.001). The results were replicated in the BIRCH and FIR data. Atezolizumab-treated patients achieving ETS had markedly improved OS compared with docetaxel-treated patients achieving ETS (24-month OS 55% vs 32%); PFS was also markedly improved (24-month PFS 31% vs 4%). In contrast, for patients not achieving ETS, atezolizumab-treatment was associated with more modest OS (24-month OS 23% vs 20%) and PFS (24-month PFS 3% vs 1%) improvement compared with docetaxel. Overall, the effect size for ETS within the atezolizumab-treated patients was significantly greater than that in the docetaxel-treated patients (P(interaction)=0.002 for OS and P(interaction)<0.001 for PFS).ConclusionsETS is an easily measurable biomarker, predictive of highly favorable survival and patient-reported outcomes with atezolizumab treatment for advanced NSCLC. Further, ETS identifies patients with significantly greater treatment benefit for ICI therapy.
Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
Authors: Trager Megan H , Coley Shana M , Dube Geoffrey , Khan Shaheer , Ingham Matthew , Samie Faramarz H , Geskin Larisa J , McDonnell Diana , Brouder Daniel , Saenger Yvonne , Carvajal Richard 
Published: June 2020

BackgroundImmune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.Case presentationsHere we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.ConclusionsThese cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.Trial Registration numberNCT03816332.
On the excitation of the $$2^+_1$$ state in $$^{12}$$C in the $$(e,e'\gamma )$$ reaction
Authors: Jakubassa-Amundsen D. H. , Ponomarev V. Yu. 
Published: June 2020

AbstractThe excitation of the carbon$$2^+$$2+state at 4.439 MeV by$$70{-}150$$70-150MeV electron impact and its subsequent decay to the ground state by photon emission is described within the distorted-wave Born approximation. The transition densities are obtained from the nuclear quasiparticle phonon model. The photon angular distributions are compared with earlier results and with experiment, including the influence of bremsstrahlung. Predictions for spin asymmetries in the case of polarized electron impact are also made.
The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-Like Phenotype
Authors: Vandamme Niels , Denecker Geertrui , Bruneel Kenneth , Blancke Gillian , Akay Özden , Taminau Joachim , De Coninck Jordy , De Smedt Eva , Skrypek Nicolas , Van Loocke Wouter , Wouters Jasper , Nittner David , Köhler Corinna , Darling Douglas S. , Cheng Phil F. , Raaijmakers Marieke I.G. , Levesque Mitchell P. , Mallya Udupi Girish , Rafferty Mairin , Balint Balazs , Gallagher William M. , Brochez Lieve , Huylebroeck Danny , Haigh Jody J. , Andries Vanessa , Rambow Florian , Van Vlierberghe Pieter , Goossens Steven , van den Oord Joost J. , Marine Jean-Christophe , Berx Geert 
Published: June 2020

Abstract

Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination.

Significance:
ZEB2 function exerts opposing behaviors in melanoma by promoting proliferation and expansion and conversely inhibiting invasiveness, which could be of future clinical relevance.