bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-collagen pathogenic variants resulting in the osteogenesis imperfecta phenotype in children: a single-country observational cohort study
Authors: Thornley Patrick , Bishop Nicholas , Baker Duncan , Brock Joanna , Arundel Paul , Burren Christine , Smithson Sarah , DeVile Catherine , Crowe Belinda , Allgrove Jeremy , Saraff Vrinda , Shaw Nick , Balasubramanian Meena 
Published: November 2021

Background/ObjectivesIn England, children (0–18 years) with severe, complex and atypical osteogenesis imperfecta (OI) are managed by four centres (Birmingham, Bristol, London, Sheffield) in a ‘Highly Specialised Service’ (HSS OI); affected children with a genetic origin for their disease that is not in COL1A1 or COL1A2 form the majority of the ‘atypical’ group, which has set criteria for entry into the service. We have used the data from the service to assess the range and frequency of non-collagen pathogenic variants resulting in OI in a single country.MethodsChildren with atypical OI were identified through the HSS OI service database. All genetic testing for children with OI in the service were undertaken at the Sheffield Diagnostic Genetics Service. Variant data were extracted and matched to individual patients. This study was done as part of a service evaluation project registered with the Sheffield Children’s Hospital Clinical Governance Department.ResultsOne hundred of 337 children in the HSS met the ‘atypical’ criteria. Eighty have had genetic testing undertaken; 72 had genetic changes detected, 67 in 13 genes known to be causative for OI. The most frequently affected genes were IFITM5 (22), P3H1 (12), SERPINF1 (8) and BMP1 (6).ConclusionAmong children with more severe forms of OI (approximately one-third of all children with OI), around 20% have pathogenic variants in non-collagen genes. IFITM5 was the most commonly affected gene, followed by genes within the P3H1 complex. These data provide additional information regarding the likelihood of different genetic origins of the disease in children with OI, which may influence clinical care.
OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study
Authors: Szeto Simon KH , Hui Vivian W. K. , Tang Fang Yao , Yang Dawei , Sun Zi han , Mohamed Shaheeda , Chan Carmen K M , Lai Timothy Y Y , Cheung Carol 
Published: November 2021

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections.MethodsThis is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.ResultsThe presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.Conclusion and relevanceBaseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.
Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours
Authors: Rico Karen , Duan Suzann , Pandey Ritu L , Chen Yuliang , Chakrabarti Jayati T , Starr Julie , Zavros Yana , Else Tobias , Katona Bryson W , Metz David C , Merchant Juanita L 
Published: November 2021

ObjectiveGastroenteropancreatic neuroendocrine tumours (GEP-NETs) encompass a diverse group of neoplasms that vary in their secretory products and in their location within the gastrointestinal tract. Their prevalence in the USA is increasing among all adult age groups.AimTo identify the possible derivation of GEP-NETs using genome-wide analyses to distinguish small intestinal neuroendocrine tumours, specifically duodenal gastrinomas (DGASTs), from pancreatic neuroendocrine tumours.DesignWhole exome sequencing and RNA-sequencing were performed on surgically resected GEP-NETs (discovery cohort). RNA transcript profiles available in the Gene Expression Omnibus were analysed using R integrated software (validation cohort). Digital spatial profiling (DSP) was used to analyse paraffin-embedded GEP-NETs. Human duodenal organoids were treated with 5 or 10 ng/mL of tumor necrosis factor alpha (TNFα) prior to qPCR and western blot analysis of neuroendocrine cell specification genes.ResultsBoth the discovery and validation cohorts of small intestinal neuroendocrine tumours induced expression of mesenchymal and calcium signalling pathways coincident with a decrease in intestine-specific genes. In particular, calcium-related, smooth muscle and cytoskeletal genes increased in DGASTs, but did not correlate with MEN1 mutation status. Interleukin 17 (IL-17) and tumor necrosis factor alpha (TNFα) signalling pathways were elevated in the DGAST RNA-sequencing. However, DSP analysis confirmed a paucity of immune cells in DGASTs compared with the adjacent tumour-associated Brunner’s glands. Immunofluorescent analysis showed production of these proinflammatory cytokines and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) by the tumours and stroma. Human duodenal organoids treated with TNFα induced neuroendocrine tumour genes, SYP, CHGA and NKX6.3.ConclusionsStromal–epithelial interactions induce proinflammatory cytokines that promote Brunner’s gland reprogramming.
General hospital specialists’ attitudes toward psychiatry: a cross-sectional survey in seven countries
Authors: Wimalaratne Inoka Koshali , McCarthy Jane , Broekman Birit F P , Nauta Klaas , Kathriarachchi Samudra , Wickramasinghe Anuprabha , Merkin Alexander , Kursakov Alexander , Gross Raz , Amsalem Doron , Wang Xiaoping , Wang Jun , de Rosalmeida Dantas Clarissa , de Carvalho Pereira Victoria , Menkes David 
Published: November 2021

ObjectivePsychiatric comorbidities are common in physical illness and significantly affect health outcomes. Attitudes of general hospital doctors toward psychiatry are important as they influence referral patterns and quality of care. Little is known about these attitudes and their cultural correlates. The aim of this study was to identify attitudes toward psychiatry among general hospital specialists in relation to culture of the practice setting and other clinician factors (gender, age, seniority and specialty).MethodsA cross-sectional, descriptive study was carried out in seven countries (New Zealand, China, Sri Lanka, Russia, Israel, Brazil, the Netherlands). Data were collected from senior medical staff of various disciplines using an updated version of Mayou and Smith’s (1986) self-administered questionnaire.ResultsA total of 889 hospital doctors participated. While favourable attitudes toward both psychiatric consultation and management were endorsed by a majority, significant differences were also observed between countries. Subgroup differences were mostly confined to gender, acuity of practice setting and specialty. For example, female doctors in Russia (χ2=7.7, p=0.0056), China (χ2=9.2, p=0.0025) and the Netherlands (χ2=5.7, p=0.0174) endorsed more positive attitudes compared with their male counterparts, but this gender effect was not replicated in the total sample. Chronic care specialists were overall more inclined to manage patients’ emotional problems compared with those working in acute care (χ2=70.8, p (adjusted)<0.0001), a significant finding seen also in individual countries (China, New Zealand, the Netherlands, Russia). Physicians were more favourably disposed toward psychiatry compared with other specialists, especially surgeons, in all countries except Israel.ConclusionsThis study adds to evidence for the association of medical attitudes with individual clinician factors and demonstrates that the influence of these factors varies by country. Understanding these issues may help to overcome barriers and improve quality of care provided to general hospital patients.
Prospective characterisation of SARS-CoV-2 infections among children presenting to tertiary paediatric hospitals across Australia in 2020: a national cohort study
Authors: Wurzel Danielle , McMinn Alissa , Hoq Monsurul , Blyth Christopher C , Burgner David , Tosif Shidan , Buttery Jim , Carr Jeremy , Clark Julia E , Cheng Allen C , Dinsmore Nicole , Francis Joshua Reginald , Kynaston Anne , Lucas Ryan , Marshall Helen , McMullan Brendan , Singh-Grewal Davinder , Wood Nicholas , Macartney Kristine , Britton Philip N , Crawford Nigel W 
Published: November 2021

ObjectiveTo present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation.DesignProspective, multicentre cohort study.SettingEight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network—Paediatric Active Enhanced Disease (PAEDS).ParticipantsAll children aged <19 years with SARS-CoV-2 infection including COVID-19, Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) and Kawasaki-like disease TS infection (KD-TS) treated at a PAEDS site from 24 March 2020 to 31 December 2020.InterventionLaboratory-confirmed SARS-CoV-2 infection.Main outcomeIncidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic.ResultsAmong 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1–12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4; KD-TS, n=1) (median 7.9 years (IQR 7.8–9.8)). Most children with COVID-19 (n=278; 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%); cardiac and respiratory comorbidities were most common (n=32/72;44%). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5; 1.3%), all were hospitalised and three (3/5; 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic.ConclusionsMost children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.
Early cisternal fibrinolysis is more effective than rescue spasmolysis for the prevention of delayed infarction after subarachnoid haemorrhage
Authors: Roelz Roland , Scheiwe Christian , Grauvogel Jürgen , Csok Istvan , Coenen Volker Arnd , Beck Jürgen , Reinacher Peter C 
Published: November 2021

BackgroundTo compare the efficacy of two different concepts of cisternal therapy—PREVENTIVE fibrinolysis plus on-demand spasmolysis versus RESCUE spasmolysis—for the prevention of cerebral vasospasm (CVS) and delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid haemorrhage (aSAH).MethodsRetrospective analysis of 84 aSAH patients selected for cisternal therapy for DCI prevention. 66 high-risk patients received PREVENTIVE cisternal therapy to enhance blood clearance. Either stereotactic catheter ventriculocisternostomy (STX-VCS) or intraoperative placement of a cisterno-ventriculostomy catheter (CVC), followed by fibrinolytic cisternal lavage using urokinase was performed. In case of vasospasm, nimodipine was applied intrathecally. 22 low-risk patients who developed CVS against expectations were selected for STX-VCS as RESCUE intervention for cisternal spasmolysis with nimodipine. Rates of DCI and mean flow velocities of daily transcranial Doppler (TCD) ultrasonographies were evaluated.ResultsDespite a higher prespecified DCI risk, patients selected for PREVENTIVE intervention primarily aiming at blood clearance had a lower DCI rate compared with patients selected for intrathecal spasmolysis as a RESCUE therapy (11.3% vs 18.2%). After intrathecal treatment onset, CVS (TCD>160 cm/s) occurred in 45% of patients with PREVENTIVE and 77% of patients with RESCUE therapy (p=0.013). A stronger response of CVS to intrathecal nimodipine was observed in patients with PREVENTIVE intervention as the mean CVS duration after start of intrathecal nimodipine was 3.2 days compared with 5.8 days in patients with RESCUE therapy (p=0.026).ConclusionsPREVENTIVE cisternal therapy directed at blood clearance is more effective for the prevention of CVS and delayed infarction compared with cisternal RESCUE spasmolysis.Trial registration numberDRKS00016532.
Fundamental energy scale of the thick brane in mimetic gravity
Authors: Sui Tao-Tao , Zhang Yu-Peng , Gu Bao-Min , Liu Yu-Xiao 
Published: November 2021

AbstractIn this paper, thick branes generated by the mimetic scalar field with Lagrange multiplier formulation are investigated. We give three typical thick brane background solutions with different asymptotic behaviors and show that all the solutions are stable under tensor perturbations. The effective potentials of the tensor perturbations exhibit as volcano potential, Poöschl–Teller potential, and harmonic oscillator potential for the three background solutions, respectively. All the tensor zero modes (massless gravitons) of the three cases can be localized on the brane. We also calculate the corrections to the four-dimensional Newtonian potential. On a large scale, the corrections to the four-dimensional Newtonian potential can be ignored. While on a small scale, the correction from the volcano-like potential is more pronounced than the other two cases. Combining the specific corrections to the four-dimensional Newtonian potential of these three cases and the latest results of short-range gravity experiments, we get the constraint on the scale parameter as $$k > rsim 10^{-4}$$

k
≳

10

-
4

eV, and constraint on the corresponding five-dimensional fundamental scale as $$M_* > rsim 10^5$$

M

∗

≳

10
5

TeV.
Thick branes in the scalar–tensor representation of f(R, T) gravity
Authors: Rosa João Luís , Marques Matheus A. , Bazeia Dionisio , Lobo Francisco S. N. 
Published: November 2021

AbstractBraneworld scenarios consider our observable universe as a brane embedded in a five-dimensional bulk. In this work, we consider thick braneworld systems in the recently proposed dynamically equivalent scalar–tensor representation of f(R, T) gravity, where R is the Ricci scalar and T the trace of the stress–energy tensor. In the general $$f\left( R,T\right) $$

f

R
,
T

case we consider two different models: a brane model without matter fields where the geometry is supported solely by the gravitational fields, and a second model where matter is described by a scalar field with a potential. The particular cases for which the function $$f\left( R,T\right) $$

f

R
,
T

is separable in the forms $$F\left( R\right) +T$$

F

R

+
T

and $$R+G\left( T\right) $$

R
+
G

T

, which give rise to scalar–tensor representations with a single auxiliary scalar field, are studied separately. The stability of the gravitational sector is investigated and the models are shown to be stable against small perturbations of the metric. Furthermore, we show that in the $$f\left( R,T\right) $$

f

R
,
T

model in the presence of an extra matter field, the shape of the graviton zero-mode develops internal structure under appropriate choices of the parameters of the model.
Long-term Mammography Adherence among Uninsured Women Enrolled in the Breast Screening and Patient Navigation (BSPAN) Program
Authors: Nair Rasmi G. , Lee Simon J. Craddock , Berry Emily , Argenbright Keith E. , Tiro Jasmin A. , Skinner Celette Sugg 
Published: November 2021

Abstract

Background:
The Breast Screening and Patient Navigation (BSPAN) Program provides access to no-cost breast cancer screening services to uninsured women in North Texas. Using data from the longitudinal BSPAN program (2012–2019), we assessed prevalence and correlates of (i) baseline adherence and (ii) longitudinal adherence to screening mammograms.

Methods:
Outcomes were baseline adherence (adherent if women received second mammogram 9–30 months after the index mammogram) and longitudinal adherence (assessed among baseline adherent women and defined as being adherent 39 months from the index mammogram). We used multivariable logistic regression and multivariable Cox proportional hazards model to assess associations of sociodemographic and clinical characteristics with baseline and longitudinal adherence, respectively.

Results:
Of 19,292 women, only 5,382 (27.9%) were baseline adherent. Baseline adherence was more likely among women who were partnered, preferred speaking Spanish, had poor reading ability, had prior Papanicolaou (PAP) testing, and prior screening mammograms, compared with women who were non-partnered, preferred speaking English, had good reading ability, had no prior PAP testing, and no prior screening mammograms, respectively. Of those who were baseline adherent, 4,364 (81.1%) women demonstrated longitudinal adherence. Correlates of longitudinal adherence were similar to those from baseline adherence.

Conclusions:
A large proportion of baseline adherent women (&gt;80%) achieved longitudinal adherence, which highlights the importance of concentrating resources during the second mammogram in the progression toward continued adherence.

Impact:
Results from our unique dataset provide realistic mammography adherence rates and may be generalizable to other areas introducing no-cost screening to low-income women, independent of any regular patient-centered medical home.
The Mitochondrial Disruptor Devimistat (CPI-613) Synergizes with Genotoxic Anticancer Drugs in Colorectal Cancer Therapy in a Bim-Dependent Manner
Authors: Arnold Carina , Demuth Philipp , Seiwert Nina , Wittmann Simon , Boengler Kerstin , Rasenberger Birgit , Christmann Markus , Huber Magdalena , Brunner Thomas , Linnebacher Michael , Fahrer Jörg 
Published: November 2021

Abstract
Colorectal cancer is one of the most frequent tumor entities, with an increasing incidence and mortality in younger adults in Europe and the United States. Five-year survival rates for advanced colorectal cancer are still low, highlighting the need for novel targets in colorectal cancer therapy. Here, we investigated the therapeutic potential of the compound devimistat (CPI-613) that targets altered mitochondrial cancer cell metabolism and its synergism with the antineoplastic drugs 5-fluorouracil (5-FU) and irinotecan (IT) in colorectal cancer. Devimistat exerted a comparable cytotoxicity in a panel of established colorectal cancer cell lines and patient-derived short-term cultures independent of their genetic and epigenetic status, whereas human colonic epithelial cells were more resistant, indicating tumor selectivity. These findings were corroborated in intestinal organoid and tumoroid models. Mechanistically, devimistat disrupted mitochondrial membrane potential and severely impaired mitochondrial respiration, resulting in colorectal cancer cell death induction independent of p53. Combination treatment of devimistat with 5-FU or IT demonstrated synergistic cell killing in colorectal cancer cells as shown by Combenefit modeling and Chou–Talalay analysis. Increased cell death induction was revealed as a major mechanism involving downregulation of antiapoptotic genes and accumulation of proapoptotic Bim, which was confirmed by its genetic knockdown. In human colorectal cancer xenograft mouse models, devimistat showed antitumor activity and synergized with IT, resulting in prolonged survival and enhanced therapeutic efficacy. In human tumor xenografts, devimistat prevented IT-triggered p53 stabilization and caused synergistic Bim induction. Taken together, our study revealed devimistat as a promising candidate in colorectal cancer therapy by synergizing with established antineoplastic drugs in vitro and in vivo.
A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage
Authors: Okwundu Nwanneka , Rahman Hafeez , Liu Tong , Florell Scott R. , Boucher Kenneth M. , Grossman Douglas 
Published: November 2021

AbstractDNA damage plays a role in ultraviolet (UV)-induced melanoma. We previously showed that aspirin (ASA) can suppress prostaglandin-E2 (PGE2) and protect melanocytes from UV-induced DNA damage in mice, and suggested that taking ASA before acute sun exposure may reduce melanoma risk. We conducted a prospective randomized placebo-controlled trial to determine if orally administered ASA could suppress PGE2 in plasma and nevi and protect nevi from UV-induced DNA damage. After obtaining plasma and determining the minimal erythemal dose (MED) in 95 subjects at increased risk for melanoma, they were randomized to receive a daily dose of placebo, 81 mg ASA, or 325 mg ASA, in double-blind fashion for one month. After this intervention, one nevus was irradiated (dose = 1 or 2 MED) using a solar simulator. One day later, MED was re-determined, a second plasma sample was obtained, and the UV-irradiated nevus and an unirradiated nevus were removed. ASA metabolites were detected in the second plasma sample in subjects in the ASA arms. There were no significant differences in the pre- and post-intervention MED between those patients receiving ASA and placebo. Significantly reduced PGE2 levels were detected in plasma (second vs. first samples) and in nevi (both unirradiated and UV-treated) in subjects receiving ASA compared to placebo. Comparing UV-treated nevi from the ASA and placebo cohorts, however, did not reveal significant reductions in CD3-cell infiltration or 8-oxoguanine and cyclobutane pyrimidine dimers. Thus ASA did not effectively protect nevi from solar-simulated UV-induced inflammation and DNA damage under the conditions examined.Prevention Relevance:Despite promising rationale, ASA at conventional dosing was not able to protect nevi against UV-induced DNA damage under the conditions examined.See related Spotlight, p. 71.