bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss‐of‐function mutations in CST6 cause dry skin, desquamation and abnormal keratosis without hypotrichosis
Authors: Wang Xuan , Liu Jun , Chen Junyi , Xu Xueyan , Zhong Yadan , Xu Yingping , Lu Ping , Zhou Jiajian , Lin Zhimiao , Yang Bin , Yang Chao 
Published: November 2022

AbstractCystatin M/E (encoded by the CST6 gene) is a cysteine protease inhibitor, that exerts regulatory and protective effects against uncontrolled proteolysis mainly by directly regulating cathepsin V, cathepsin L, and legumain activities. Previous studies have suggested that CST6 may exert a regulatory role in epidermal differentiation and hair follicle formation by inhibiting the activity of respective cognate target proteases. However, until recently, studies have revealed that loss‐ or gain‐of‐function of the CST6 gene causes dry skin with hypotrichosis in humans. Here, we reported two siblings of Chinese origin with dry skin, desquamation and abnormal keratosis without hypotrichosis. By applying whole‐exome sequencing, we identified homozygous loss‐of‐function mutation c.251G > A (p.Gly84Asp) in the CST6 gene as the underlying genetic cause. Further fluorimetric enzyme assays demonstrated the mutant cystatin M/E protein lost its inhibitory function on the protease activity of cathepsins. Moreover, the corresponding mutation in mice resulted in excessive cornification, desquamation, impaired skin barrier function, and abnormal proliferation and differentiation of keratinocytes. In conclusion, the homozygous missense mutation c.251G > A in CST6 gene resulted in dry skin, desquamation, as well as abnormal keratosis of the skin, promoting our understanding of the role of protease‐antiprotease balance in human skin disorders.
Evolving capacity of children and their best interests in the context of health research in South Africa: An ethico‐legal position
Authors: Labuschaigne Melodie , Mahomed Safia , Dhai Ames 
Published: November 2022

AbstractThe existing ethico‐legal regulation of adolescent children's participation in health research in South Africa is currently unclear. The article interrogates the existing framework governing children's consent to research participation, with specific emphasis on discrepancies in consent norms in law and ethical guidelines. Against the backdrop of the constitutional directive that requires that a child's best interests are of paramount importance in every matter concerning the child, the article assesses whether sufficient consideration is given to children's evolving maturity and capacities when consent to their participation in health research is sought. The article provides specific recommendations and proposes a legislative change to consent provisions in the National Health Act 61 of 2003 in order to address the existing lacunae and to align the framework with constitutional imperatives and international fundamental rights considerations.
Burden of established cardiovascular disease in people with type 2 diabetes and matched controls: Hospital‐based care, days absent from work, costs and mortality
Authors: Persson Sofie , Nilsson Kristoffer , Karlsdotter Kristina , Skogsberg Josefin , Gustavsson Staffan , Jendle Johan , Steen Carlsson Katarina 
Published: November 2022

AbstractAimsTo assess hospital‐based care, work absence, associated costs, and mortality in patients with type 2 diabetes with and without established cardiovascular disease (eCVD) compared to matched controls.Materials and methodsIn a population‐based cohort study, we analysed individual‐level data from national health, social insurance and socio‐economic registers for people diagnosed with type 2 diabetes before age 70 years and controls (5:1) in Sweden. Regression analysis was used to attribute costs and days absent due to eCVD. Mortality was analysed using Cox proportional hazard regression, stratified by birth year and adjusted for sex and education.ResultsThirty percent (n = 136 135 of 454 983) of people with type 2 diabetes had ≥1 person‐year with eCVD (women 24%; men 34%). The mean annual costs of hospital‐based care for diabetes complications were EUR 2629 (95% confidence interval [CI] 2601‐2657) of which EUR 2337 (95% CI 2309‐2365) were attributed to eCVD (89%). The most costly person‐years (10th percentile) were observed in a broad subgroup, 42% of people with type 2 diabetes and eCVD. People with type 2 diabetes had on average 146 days absent (95% CI 145‐147) per year, of which 68 days (47%; 95% CI 67‐70) were attributed to eCVD. The mortality hazard ratio for type 2 diabetes with eCVD was 4.63 (95%CI 4.58‐4.68) and without eCVD was 1.86 (95% CI 1.84‐1.88) compared to controls without eCVD.ConclusionThe sizable burden of eCVD on both the individual with type 2 diabetes and society calls for efficient management in order to reduce the risks for those living with eCVD and to postpone its onset.
Model‐based predictions on health benefits and budget impact of implementing empagliflozin in people with type 2 diabetes and established cardiovascular disease
Authors: Nilsson Kristoffer , Andersson Emelie , Persson Sofie , Karlsdotter Kristina , Skogsberg Josefin , Gustavsson Staffan , Jendle Johan , Steen Carlsson Katarina 
Published: November 2022

AbstractAimTo perform a model‐based analysis of the short‐ and long‐term health benefits and costs of further increased implementation of empagliflozin for people with type 2 diabetes and established cardiovascular disease (eCVD) in Sweden.Materials and MethodsThe validated Institute for Health Economics Diabetes Cohort Model (IHE‐DCM) was used to estimate health benefits and a 3‐year budget impact, and lifetime costs per quality‐adjusted life years (QALY) gained of increased implementation of adding empagliflozin to standard of care (SoC) for people with type 2 diabetes and eCVD in a Swedish setting. Scenarios with 100%/75%/50% implementation were explored. Analyses were based on 30 model cohorts with type 2 diabetes and eCVD (n = 131 412 at baseline) from national health data registers. Sensitivity analyses explored the robustness of results.ResultsOver 3 years, SoC with empagliflozin (100% implementation) versus SoC before empagliflozin resulted in 7700 total life years gained and reductions in cumulative incidence of cardiovascular deaths by 30% and heart failures by 28%. Annual costs increased by 15% from higher treatment costs and increased survival. Half of these benefits and costs are not yet reached with current implementation below 50%. SoC with empagliflozin yielded 0.37 QALYs per person, with an incremental cost‐effectiveness ratio of 16 000 EUR per QALY versus SoC before empagliflozin.ConclusionsModel simulations using real‐world data and trial treatment effects indicated that a broader implementation of empagliflozin, in line with current guidelines for treatment of people with type 2 diabetes and eCVD, would lead to further benefits even from a short‐term perspective.
Lyme neuroborreliosis with antibodies in cerebrospinal fluid but not in serum
Authors: Zomer Tizza P. , Bruinsma Reitze , van Samkar Anusha , Vermeeren Yolande M. , Wieberdink Renske G. , van Kooten Barend , van Bemmel Thomas 
Published: November 2022

AbstractBackground and purposeTo diagnose Lyme neuroborreliosis (LNB), cerebrospinal fluid (CSF) is tested for pleocytosis and intrathecal antibody production. The Dutch guideline for Lyme borreliosis indicates a lumbar puncture in the case of positive Borrelia serology or a strong clinical suspicion of LNB. This suggests that LNB might be underdiagnosed in patients with negative Borrelia serology and/or a minor clinical suspicion. The objective was to assess how often negative Borrelia serology occurs in the case of LNB.MethodA retrospective study was performed among patients with LNB visiting Gelre Hospitals between January 2007 and December 2020. Electronic medical records of patients with pleocytosis were reviewed to identify patients with LNB. Data were collected from medical records.ResultsIncluded were 127 patients with LNB, 58 of whom were children. In 67 patients Borrelia antibodies were present in both serum and CSF. In 53 of 67 patients there was intrathecal antibody production. In 28 patients there was intrathecal antibody production but serum antibodies were absent. Of patients with positive serology 77% had antibodies in CSF versus 83% of patients with negative serology (p = 0.435). Of patients with positive serology 61% had intrathecal antibody production versus 78% of patients with negative serology (p = 0.073).ConclusionsTwenty‐eight LNB patients had intrathecal antibody production but no antibodies in serum. In this specific patient population, positive serum serology was not associated with antibodies in CSF nor with intrathecal antibody production. In Lyme endemic areas, in patients with symptoms suggestive for LNB, there is a need to lower the threshold for a lumbar puncture.
Cost‐effectiveness of surgical treatment compared to medical treatment in patients with drug‐refractory epilepsy: A systematic review
Authors: Kitschen Anne , Aleknonytė‐Resch Milda , Sakalytė Gabija , Diederich Freya 
Published: November 2022

AbstractBackground and purposeApproximately 30% of epilepsy patients develop a drug‐refractory epilepsy, that is, seizures cannot be controlled with antiepileptic drugs. Surgery has been evaluated as an effective but costly form of treatment. The aim of this systematic review is to synthesize the available evidence on the cost‐effectiveness of surgical treatment compared to medical treatment for these patients.MethodA systematic literature search was performed in MEDLINE, Embase, PsycINFO, Cochrane Library and the National Health Service Economic Evaluation Database until September 2022. Title, abstract and full‐text screening were conducted by two researchers. Original studies published in English or German analyzing the cost‐effectiveness of surgical compared to medical treatment were included. Study characteristics, effectiveness measures, costs and incremental cost‐effectiveness ratios (ICERs) were extracted. The quality of studies was assessed using the Drummond checklist.ResultsFourteen studies were included. Most studies evaluated surgery as cost‐effective. The ICER per patient seizure free ranged from dominant to purchasing power parity US dollars (PPP‐USD) 479,275. The ICER per 1% seizure reduction ranged from PPP‐USD 227 to PPP‐USD 342. The ICER per year without seizures was PPP‐USD 4202 and the ICER per quality‐adjusted life‐year ranged from dominant to PPP‐USD 90,874. The studies varied greatly in their methodology and time horizon.ConclusionSurgical treatment is cost‐effective compared to medical treatment, especially when a lifetime horizon is adopted. It is concluded that all disease‐specific costs should be considered over a long period when assessing the cost‐effectiveness of epilepsy treatment. From an economic perspective, efforts should be made to improve access to surgical treatment for patients with drug‐refractory epilepsy.
Comparing radiographic scores for prediction of complications and outcome of aneurysmal subarachnoid hemorrhage: Which performs best?
Authors: Said Maryam , Odensass Svenja , Gümüs Meltem , Rodemerk Jan , Chihi Mehdi , Rauschenbach Laurèl , Dinger Thiemo Florin , Darkwah Oppong Marvin , Dammann Philipp , Wrede Karsten Henning , Sure Ulrich , Jabbarli Ramazan 
Published: November 2022

AbstractBackground and purposeAneurysmal subarachnoid hemorrhage (aSAH) is characterized by high morbidity and mortality proceeding from the initial severity and following complications of aSAH. Various scores have been developed to predict these risks. We aimed to analyze the clinical value of different radiographic scores for prognostication of aSAH outcome.MethodsInitial computed tomography scans (≤48 h after ictus) of 745 aSAH cases treated between January 2003 and June 2016 were reviewed with regard to Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and Claassen, Barrow Neurological Institute (BNI), Hijdra, original Graeb and Fisher scale scores. The primary endpoints were development of delayed cerebral ischemia (DCI), in‐hospital mortality and unfavorable outcome (modified Rankin Scale score >3) at 6 months after subarachnoid hemorrhage. Secondary endpoints included the different complications that can occur during aSAH. Clinically relevant cutoffs were defined using receiver‐operating characteristic curves. The radiographic scores with the highest values for area under the curve (AUC) were included in the final multivariate analysis.ResultsThe Hijdra sum score had the most accurate predictive value and independent associations with all primary endpoints: DCI (AUC 0.678, adjusted odds ratio [aOR] 2.83; p < 0.0001); in‐hospital mortality (AUC 0.704, aOR 2.83; p < 0.0001) and unfavorable outcome (AUC 0.726, aOR 2.91; p < 0.0001). Multivariate analyses confirmed the independent predictive value of the radiographic scales for risk of decompressive craniectomy (SEBES and Fisher score), cerebral vasospasm (SEBES, BNI score and Fisher score) and shunt dependency (Hijdra ventricle score and Fisher score) after aSAH.ConclusionsInitial radiographic severity of aSAH was independently associated with occurrence of different complications during aSAH and the final outcome. The Hijdra sum score showed the highest diagnostic accuracy and robust predictive value for early detection of risk of DCI, in‐hospital mortality and unfavorable outcome after aSAH.
Apparent thermal acclimation of soil heterotrophic respiration mainly mediated by substrate availability
Authors: He Yanghui , Zhou Xuhui , Jia Zhen , Zhou Lingyan , Chen Hongyang , Liu Ruiqiang , Du Zhenggang , Zhou Guiyao , Shao Junjiong , Ding Junxia , Chen Kelong , Hartley Iain P. 
Published: November 2022

AbstractMultiple lines of existing evidence suggest that increasing CO2 emission from soils in response to rising temperature could accelerate global warming. However, in experimental studies, the initial positive response of soil heterotrophic respiration (RH) to warming often weakens over time (referred to apparent thermal acclimation). If the decreased RH is driven by thermal adaptation of soil microbial community, the potential for soil carbon (C) losses would be reduced substantially. In the meanwhile, the response could equally be caused by substrate depletion, and would then reflect the gradual loss of soil C. To address uncertainties regarding the causes of apparent thermal acclimation, we carried out sterilization and inoculation experiments using the soil samples from an alpine meadow with 6 years of warming and nitrogen (N) addition. We demonstrate that substrate depletion, rather than microbial adaptation, determined the response of RH to long‐term warming. Furthermore, N addition appeared to alleviate the apparent acclimation of RH to warming. Our study provides strong empirical support for substrate availability being the cause of the apparent acclimation of soil microbial respiration to temperature. Thus, these mechanistic insights could facilitate efforts of biogeochemical modeling to accurately project soil C stocks in the future climate.
Switching defective/sucrose non‐fermenting chromatin remodeling complex coordinates meiotic gene activation via promoter remodeling and Meiosin activation in female germline
Authors: Ito Toshiaki , Ohta Masami , Osada Atsuki , Nishiyama Akira , Ishiguro Kei‐Ichiro , Tamura Tomohiko , Sekita Yoichi , Kimura Tohru 
Published: November 2022

AbstractIn mammals, primordial germ cells (PGCs) enter meiosis and differentiate into primary oocytes in embryonic ovaries. Previously, we demonstrated that meiotic gene induction and meiotic initiation were impaired in female germline cells of conditional knockout (CKO) mice lacking the Smarcb1 (Snf5) gene, which encodes a core subunit of the switching defective/sucrose non‐fermenting (SWI/SNF) complex. In this study, we classified meiotic genes expressed at lower levels in Snf5 CKO females into two groups based on promoter accessibility. The promoters of 74% of these genes showed lower accessibility in mutant mice, whereas those of the remaining genes were opened without the SWI/SNF complex. Notably, the former genes included Meiosin, which encodes a transcriptional regulator essential for meiotic gene activation. The promoters of the former and the latter genes were mainly modified with H3K27me3/bivalent and H3K4me3 histone marks, respectively. A subset of the former genes was precociously activated in female PGCs deficient in polycomb repressive complexes (PRCs). Our results point to a mechanism through which the SWI/SNF complex coordinates meiotic gene activation via the remodeling of PRC‐repressed genes, including Meiosin, in female germline cells.
Controlled synthesis of Bi2O3–YSZ composite powders and their sintering behavior for high‐performance electrolytes
Authors: Tian Yuhang , Liu Shuangshuang , Zhang Xu , Xiao Shikang , Sun Jian , Zhang Jingde , Han Guifang 
Published: November 2022

AbstractBismuth oxide (Bi2O3) is a promising additive to decrease the sintering temperature of yttria‐stabilized zirconia (YSZ)‐based electrolyte for solid oxide fuel cell application. However, Bi2O3 tends to grow into large column bars (>50 µm) in a chemical coprecipitation method, which dramatically limits the mixing uniformity of Bi2O3 and YSZ, even much worse than that of mechanical mixing. In this study, the reaction temperature was increased from room temperature to 90°C to increase the number of nucleation during the violate reaction between Bi3+ solution and YSZ suspension in NaOH. On this basis, the violence of the reaction was further moderated by adding half of NaOH first, then YSZ powders and the other half of an NaOH solution. The size of Bi2O3 was further decreased to sub‐micrometer and Bi2O3 was homogeneously mixed with YSZ particles, even when its addition amount was as large as 20 mol%. These composite powders effectively promoted the sintering behavior of YSZ. The sintering temperature of YSZ was decreased to 900 and 1000°C with 10 and 5 mol% Bi2O3 doping, respectively. Increasing the doping ratio induced severe volatilization of Bi2O3 and pore formation. Raising the sintering temperature (no more than 1200°C) enhanced the doping effect of Bi2O3 into the YSZ lattice but induced instability in the YSZ crystal structure.
Easy control of surface morphology through a natural phenomenon
Authors: Ishikawa Toshihiro , Niidome Katsuya 
Published: November 2022

AbstractThis paper provides an innovative controlling process of surface morphology. The contact area between a liquid and a solid is strongly affected by the critical surface tension (cft) of both materials. Using this phenomenon, a wide range of morphologies, from flat surface layers to sea‐grape‐like surface structures, were created. Due to the bleed‐out phenomenon, low‐molecular‐mass additive (liquid) oozed out of a precursor polymer (solid), leading to different surface morphologies depending on the cft values of the liquid (Mcft) and solid (Pcft). When Mcft < < Pcft, a flat surface layer was obtained; however, in the case of Pcft < < Mcft, the formation of a sea‐grape‐like surface layer was created. Tetra‐butoxy‐titanium and polydimethylsiloxane were used as low‐molecular‐mass additive and precursor polymer, respectively. After coating on titanium metal and calcination, sea‐grape‐like materials composed of titanium oxide and silicon oxide were obtained. Furthermore, unique characteristics (bioactivity, photocatalytic activity, and prevention of atomic diffusion) were observed. A remarkable increase in the wettability, bioactivity, and catalytic activity of materials was achieved using our simple process to create unique surface morphologies. Our proposed process is applicable to a wide range of materials and morphologies, and can be used in catalysts, biomaterials, and environmental barrier coatings.
Combination repair of nasal ala and nasolabial fold defects following Mohs micrographic surgery
Authors: Cervantes Jose A. , Deen Sidra , Shimizu Ikue 
Published: November 2022

AbstractBackgroundRepair of excisional defects involving the nose and cheek requires thoughtful planning to maintain the natural contour of the anatomical sites and optimize cosmetic outcomes. We aim to demonstrate that a combination repair of defects involving the ala and nasolabial fold with a full‐thickness skin graft and a local flap can be used with good cosmesis and minimal complications.MethodsThis is a case report of a patient with skin cancer on the left ala and left nasolabial fold who underwent Mohs micrographic surgery for tumor extirpation.ResultsThe patient and the Mohs surgeon reported satisfaction with the cosmetic and functional outcomes at the 6‐month postoperative follow‐up with no complications.ConclusionThe use of a full‐thickness skin graft from a standing tissue cone and a cheek crescentic advancement flap is a viable repair option for Mohs micrographic surgery defects involving the ala and nasolabial fold.
Australia and New Zealand Transplant and Cellular Therapies (ANZTCT) position statement: COVID‐19 management in patients with haemopoietic stem cell transplant and chimeric antigen receptor T cell
Authors: Perram Jacinta , Purtill Duncan , Bajel Ashish , Butler Jason , O'Brien Tracey , Teh Benjamin , Gilroy Nicole , Ho Phoebe J. , Doocey Richard , Hills Thomas , Perera Travis , Douglas Genevieve , Ramachandran Shanti , Chee Lynette , Trotman Judith , Weinkove Robert , Keogh Steven , Fraser Chris , Cochrane Tara , Watson Anne‐Marie , Diamond Peter , Latimer Maya , Irving Ian , Blyth Emily , Cheah Chan , Cole Theresa , Milliken Sam , Yang Hung , Greenwood Matthew , Bardy Peter , Kennedy Glen , Larsen Stephen , Conyers Rachel , Hamad Nada 
Published: November 2022

AbstractPatients with post‐haemopoietic stem cell transplant or chimeric antigen receptor T ‐cell (CAR‐T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high‐risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.
TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display
Authors: Molinari Paula , Crespo María Inés , Molina Guido N. , Dho Nicolás D. , Marinho Fábio V. , Maletto Belkys , Leclerc Claude , Oliveira Sergio C. , Taboga Oscar , Cebrian Ignacio , Morón Gabriel 
Published: November 2022

AbstractAlthough the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class‐I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL‐12 production by DCs are TLR9‐dependent and STING‐independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus‐based vaccines development.