bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introduction of General Chapters on standard methods for allergen quantification in the European Pharmacopoeia
Authors: Zimmer Julia , Bonertz Andreas , Kaul Susanne , Vieths Stefan 
Published: December 2022

AbstractThe Biological Standardization Project BSP090 has been successfully concluded in 2021. As a result, two standard methods for quantification of the major allergens Bet v 1 and Phl p 5 will be implemented in the European Pharmacopoeia (Ph. Eur.). The General Chapter describing the protocol of the respective Bet v 1‐specific ELISA has already been adopted by the Ph. Eur. Commission and will become an official part of the Ph. Eur. in the beginning of 2023. As this will be the first allergen‐specific standard method in the EU, this paper intends to summarize the preceding process and outline the measures necessary to comply with the new regulatory requirement.
Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors
Authors: Carbonnel Franck , Routier Emilie , Lazure Thierry , Mussini Charlotte , Bellanger Christophe , Merklen Carine , Bejou Bakhtiar , Buisson Anthony , Amiot Aurélien , Meyer Antoine , Dong Catherine , Robert Caroline 
Published: December 2022

SummaryBackground and AimsDual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors.MethodsWe studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally.ResultsBetween January 2021 and March 2022, nine women and one man, aged 50–90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis.ConclusionBRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon.
Contributions of cognitive flexibility, inhibition and number label knowledge to numerical equivalence in 3‐ to 5‐year‐old children
Authors: Chen Yinghe , Han Congcong , Yu Xiao , Yang Xiujie , Jiang Jiali , Zhao Yuxi 
Published: December 2022

AbstractTo investigate the contributions of cognitive flexibility, inhibition and number label knowledge to children's numerical equivalence, one hundred and one 3‐ to 5‐year‐olds were administered the dimensional change card sorting task, the day‐night task and the give‐a‐number task. The numerical equivalence was assessed with the numerical matching task in three surface similarity conditions. Results showed that, in the high surface similarity condition, cognitive flexibility and label knowledge, rather than inhibition, were significant predictors of children's performance in numerical equivalence. In the low surface similarity and the cross‐mapping conditions, only cognitive flexibility, rather than number label knowledge and inhibition, significantly explained the unique variance in numerical equivalence. Besides, cognitive flexibility explained more variation in numerical equivalence in the cross‐mapping condition compared with the low surface similarity condition. These findings highlight different roles of cognitive flexibility, inhibition and number label knowledge in numerical equivalence in the three surface similarity conditions.
Soft tissue esthetics around immediately provisionalized delayed implants with and without connective tissue graft: A randomized clinical trial pilot study
Authors: Abdelwahab Dina , Ezz AlArab Azza , El Nahass Hani 
Published: December 2022

AbstractObjectiveEvaluate the peri‐implant soft tissue esthetics following a single, immediately provisionalized, delayed implant with/‐out subepithelial connective tissue graft (SCTG).Material and MethodsThe eligible patients were randomized into two groups. Immediate provisionalization was performed with (test group: SCTGG) or without SCTG (control group: NGG). The soft tissue esthetics was assessed by Pink Esthetic Score (PES) and Mucosal Scarring Index (MSI), at 6 and 12 months, following final implant restoration.ResultsThe SCTGG, compared to NGG, yielded a 0.2 increased PES at 12 months (95% confidence interval (CI): −1, 1.4) and a 0.2 decreased MSI score (95% CI −0.9, 0.5) with no statistically significant differences in PES and MSI between both groups (p > 0.05).ConclusionSoft tissue grafting around immediately provisionalized delayed implants could exhibit comparable results to immediate provisionalization alone in terms of peri‐implant soft tissue esthetics using PES and MSI (ClinicalTrials.gov Identifier: NCT03770975).
Smurf1 regulates ameloblast polarization by ubiquitination‐mediated degradation of RhoA
Authors: Niu Haoman , Bi Fei , Zhao Wenjun , Xu Yuchan , Han Qi , Guo Weihua , Chen Yu 
Published: December 2022

AbstractCell polarity is essential for ameloblast differentiation and enamel formation. Smurf1 can mediate cell polarization through ubiquitination degradation of specific substrates. But it remains unclear whether Smurf1 could regulate ameloblast polarity and the underlying mechanism. Here, immuno‐fluorescence staining and RT‐qPCR were applied to detect the expression of Smurf1 and F‐actin. A mouse lower incisor defect model was constructed. Scanning electron microscope, rat lower incisor culture, western blot, wound healing assay and trans‐well migration assay were performed to detect the influence of Smurf1 knockdown on ameloblast. IF double staining, western blot and co‐immunoprecipitation were conducted to detect the interaction between Smurf1 and RhoA. The in vivo experiment was also performed. We found that Smurf1 was mainly expressed in the membrane and cell cortex of ameloblast, similar to F‐actin. Smurf1 expression increased along ameloblast polarization and differentiation. After knocking down Smurf1, the cytoskeleton and cell morphology changed and the cell polarity was damaged. Smurf1 regulated ameloblast polarity through ubiquitination degradation of activated RhoA in vitro. Local knockdown of Smurf1 in rat lower incisor ameloblast resulted in ameloblast polarity loss, enamel matrix secretion disorder and chalky enamel, but RhoA inhibitor Y‐27632 could reverse this effect. Collectively, Smurf1 could regulate the polarization of ameloblast through ubiquitination degradation of activated RhoA, which contributed to the knowledge of tooth development and provided new research ideas for cell polarity.
Amplifying Resilient Communities: Identifying Resilient Community Practices to Better Inform Health System Design
Authors: RAJ ROMIT , GEORGE BABITHA , MARONA CRISTIN , WEST REBECCA , GOMEZ ANABEL , JOHNSON TRACY PILAR , PRAKASH ADITYA , SHARMA SUNNY , BIYANI AYUSHI , BARUA MRITTIKA , BRUNS CAL 
Published: December 2022

Globally, the COVID‐19 pandemic has been an inflection point, bringing heightened awareness around the preparedness and resilience of public health systems in dealing with severe shocks. While the pandemic has accentuated the existing weakness in public health systems, for many, especially those belonging to marginalized sections of society, seeking healthcare has always been fraught with severe challenges and frictions.This paper presents the findings from a two‐year design research project conducted in South Africa and Bangladesh, which studied the challenges faced by health seekers, especially those whose ability to access healthcare is compromised by a range of vulnerabilities. These populations display remarkably adaptive behaviors and innovations that are aimed at mitigating the lacunae in public health systems.In our analysis, these lacunae are articulated as points of friction, which are the gaps between the expectations of health seekers while accessing healthcare and the ability of health systems to meet these expectations. For vulnerable communities, these points of friction are often accentuated and more acutely felt. Taking a design thinking lens, we see these points of friction as opportunities for change that can potentially drive innovations in the public health space, leading to better health outcomes. The paper concludes with a set of design principles, which are meant to address the frictions identified during the course of the study and inform more user centered health systems in the future.
Enhancing the structural diversity between forest patches—A concept and real‐world experiment to study biodiversity, multifunctionality and forest resilience across spatial scales
Authors: Müller Jörg , Mitesser Oliver , Cadotte Marc W. , van der Plas Fons , Mori Akira S. , Ammer Christian , Chao Anne , Scherer‐Lorenzen Michael , Baldrian Petr , Bässler Claus , Biedermann Peter , Cesarz Simone , Claßen Alice , Delory Benjamin M. , Feldhaar Heike , Fichtner Andreas , Hothorn Torsten , Kuenzer Claudia , Peters Marcell K. , Pierick Kerstin , Schmitt Thomas , Schuldt Bernhard , Seidel Dominik , Six Diana , Steffan‐Dewenter Ingolf , Thorn Simon , von Oheimb Goddert , Wegmann Martin , Weisser Wolfgang W. , Eisenhauer Nico 
Published: December 2022

AbstractIntensification of land use by humans has led to a homogenization of landscapes and decreasing resilience of ecosystems globally due to a loss of biodiversity, including the majority of forests. Biodiversity–ecosystem functioning (BEF) research has provided compelling evidence for a positive effect of biodiversity on ecosystem functions and services at the local (α‐diversity) scale, but we largely lack empirical evidence on how the loss of between‐patch β‐diversity affects biodiversity and multifunctionality at the landscape scale (γ‐diversity). Here, we present a novel concept and experimental framework for elucidating BEF patterns at α‐, β‐, and γ‐scales in real landscapes at a forest management‐relevant scale. We examine this framework using 22 temperate broadleaf production forests, dominated by Fagus sylvatica. In 11 of these forests, we manipulated the structure between forest patches by increasing variation in canopy cover and deadwood. We hypothesized that an increase in landscape heterogeneity would enhance the β‐diversity of different trophic levels, as well as the β‐functionality of various ecosystem functions. We will develop a new statistical framework for BEF studies extending across scales and incorporating biodiversity measures from taxonomic to functional to phylogenetic diversity using Hill numbers. We will further expand the Hill number concept to multifunctionality allowing the decomposition of γ‐multifunctionality into α‐ and β‐components. Combining this analytic framework with our experimental data will allow us to test how an increase in between patch heterogeneity affects biodiversity and multifunctionality across spatial scales and trophic levels to help inform and improve forest resilience under climate change. Such an integrative concept for biodiversity and functionality, including spatial scales and multiple aspects of diversity and multifunctionality as well as physical and environmental structure in forests, will go far beyond the current widely applied approach in forestry to increase resilience of future forests through the manipulation of tree species composition.
Visual interstitial fibrosis assessment as continuous variable in protocol renal transplant biopsies
Authors: Keijbeck Anke , Raaijmaakers Anniek , Hillen Lisa , Gelens Marielle , van Kuijk Sander , Cleutjens Jack P M , Peutz‐Kootstra Carine , Christiaans Maarten 
Published: December 2022

AimsIn current renal transplant pathology practice, interstitial fibrosis is visually assessed in categories according to the Banff classification. As this has a moderate reproducibility, which is little ameliorated by morphometric analysis, we investigated whether visual renal fibrosis assessment is feasible on a continuous scale, i.e. as a percentage of affected area of the cortex.Methods and resultsProtocol renal biopsies taken at transplantation (n = 125), three (n = 73) and 12 months (n = 88) after transplantation were visually scored in categories (Banff) and percentages for interstitial fibrosis (ci). Interobserver variation (ICC and weighted κ) was assessed, and morphometric analysis on Sirius red‐stained sections was performed. Correlations between the different methods and their association with donor age and eGFR 1 and 5 years post‐transplant were analysed using Pearson's or Spearman's rho. Interobserver agreement was equivalent for Banff and %ci (κ = 0.713 versus ICC = 0.792), and for Banff IF/TA and %IF/TA (κ = 0.615 versus ICC = 0.743). Both Banff and %ci were associated with Sirius red morphometry in 3 and 12 months. With all three methods, a significant correlation was found between donor age and fibrosis in the implantation biopsy and between fibrosis in the 12 months’ biopsy and eGFR at 1 and 5 years (eGFR at 1 year: Sirius red ρ = 0.487, %ci ρ = 0.393, Banff ρ = 0.413, all P < 0.01, eGFR at 5 years: Sirius red ρ = 0.392, %ci ρ = 0.333, Banff ρ = 0.435, all P < 0.01).ConclusionInterstitial fibrosis assessment on a continuous scale can be used next to scoring in categories according to the Banff classification in protocol renal transplant biopsies.
Tooth loss and periodontal status in patients with cardiovascular disease in the Serbian population: A randomized prospective study
Authors: Pejcic Ana , Kostic Milena , Marko Igic , Obradovic Radmila , Minic Ivan , Bradic‐Vasic Marija , Gligorijevic Nikola , Kurtagic Dzemil 
Published: December 2022

AbstractObjectivesChronic periodontal infections may predispose to cardiovascular disease. Since tooth loss may be due to periodontitis it is assumed that tooth loss can also predisposes cardiovascular disease. The aim was to investigate the possible relationship between the severity of the clinical picture of periodontitis and the occurrence of cardiovascular disease.MethodsWe evaluated the association between clinical periodontal parameters, tooth loss and cardiovascular incident. A total of 100 subjects (50 subjects diagnosed with cardiovascular disease and 50 in control group without cardiovascular disease) underwent a dental examination. Tooth loss in all participants was caused only as a consequence of periodontitis. In addition to periodontal status, conventional risk factors for cardiovascular diseases (hypertension, smoking, obesity, hypercholesterolemia, diabetes) were measured, too.ResultsPeriodontal status was worse in patients in the group with cardiovascular disease compared to the group without cardiovascular disease. A significant association was observed between tooth loss levels and cardiovascular disease. In the group of patients who had cardiovascular disease, tooth loss was more than 50%. In the group of patients without cardiovascular disease, tooth loss was about 20% of the total number of teeth. A significant association was observed between tooth loss levels and cardiovascular disease prevalence.ConclusionThis study presents relationship between number of teeth and cardiovascular disease, indicating a link between oral health and cardiovascular disease.
A comparative study on nivolumab and axitinib as secondary treatment in patients with metastatic renal cell carcinoma: A multi‐institutional retrospective study in Japan
Authors: Kato Taigo , Yumiba Satoru , Nakata Wataru , Nakano Kosuke , Nagahara Akira , Matsuzaki Kyosuke , Hayashi Yujiro , Hatano Koji , Kawashima Atsunari , Takao Tetsuya , Nishimura Kensaku , Nakai Yasutomo , Nakayama Masashi , Nishimura Kazuo , Takada Shingo , Tsujihata Masao , Uemura Motohide , Nonomura Norio , Imamura Ryoichi 
Published: December 2022

ObjectivesWhen primary treatment has been inadequate, nivolumab and axitinib are often used as a secondary treatments for patients with metastatic renal cell carcinoma (mRCC). However, there have been few reports comparing the efficacy and safety of these drugs.MethodsWe retrospectively investigated 58 patients treated with nivolumab and 57 patients treated with axitinib as secondary treatment between April 2013 and December 2019. We then assessed the clinical efficacy and safety of the treatments in both groups.ResultsThe most common primary therapy was sunitinib (61.7%). Both nivolumab and axitinib groups showed no significant differences in terms of the objective response rate and disease control rate (p = 0.280 and p = 0.518, respectively). Importantly, progression‐free survival (PFS) and overall survival (OS) seemed to be similar in patients treated with nivolumab and axitinib (p = 0.527 and p = 0.266, respectively), irrespective of the objective response to primary therapy. Furthermore, a Cox proportional hazards model showed that pretreatment Karnofsky Performance Status was significantly associated with PFS and OS. Although the incidence of adverse events was significantly higher in the patients treated with axitinib, there was no significant difference in time to treatment failure between the two groups.ConclusionsNivolumab and axitinib showed similar clinical benefits as secondary treatment in patients with mRCC; thus, they should be an option in sequential therapy following treatment with tyrosine kinase inhibitors (TKIs). Future studies and feasible therapeutic biomarkers would help predict the clinical response to TKIs or immune checkpoint inhibitors in patients with mRCC.
RNF7 promotes glioma growth via the PI3K/AKT signalling axis
Authors: Tang Nan , Zhu Kai , Jiang Cheng , Xiong Zhiyong , Wang Qiangping , Li Junjun , Xu Weiming 
Published: December 2022

AbstractRNF7 has been reported to play critical roles in various cancers. However, the underlying mechanisms of RNF7 in glioma development remain largely unknown. Herein, the expression level of RNF7 was examined in tissues by quantitative real‐time PCR, Western blotting and immunohistochemistry. The effect of RNF7 on glioma progression was measured by performing CCK‐8 and apoptosis assays, cell cycle‐related experiments and animal experiments. The effect of RNF7 on PI3K/AKT signalling pathway was tested by Western blotting. First, we found that RNF7 was upregulated in tumour tissue compared with normal brain tissue, especially in high‐grade glioma, and the high expression of RNF7 was significantly related to tumour size, Karnofsky Performance Scale score and a poor prognosis. Second, RNF7 overexpression facilitated tumour cell cycle progression and cell proliferation and suppressed apoptosis. Conversely, RNF7 knockdown suppressed tumour cell cycle progression and cell proliferation and facilitated apoptosis. Furthermore, follow‐up mechanistic studies indicated that RNF7 could facilitate glioma cell proliferation and cell cycle progression and inhibit apoptosis by activating the PI3K/AKT signalling pathway. This study shows that RNF7 can clearly promote glioma cell proliferation by facilitating cell cycle progression and inhibiting apoptosis by activating the PI3K/AKT signalling pathway. Targeting the RNF7/PI3K/AKT axis may provide a new perspective on the prevention or treatment of glioma.
Formation of multicellular colonies by choanoflagellates increases susceptibility to capture by amoeboid predators
Authors: Chin Nicole E. , Wu Tiffany C. , O'Toole J. Michael , Xu Kevin , Hata Tom , Koehl Mimi A. R. 
Published: December 2022

AbstractMany heterotrophic microbial eukaryotes are size‐selective feeders. Some microorganisms increase their size by forming multicellular colonies. We used choanoflagellates, Salpingoeca helianthica, which can be unicellular or form multicellular colonies, to study the effects of multicellularity on vulnerability to predation by the raptorial protozoan predator, Amoeba proteus, which captures prey with pseudopodia. Videomicrography used to measure the behavior of interacting S. helianthica and A. proteus revealed that large choanoflagellate colonies were more susceptible to capture than were small colonies or single cells. Swimming colonies produced larger flow fields than did swimming unicellular choanoflagellates, and the distance of S. helianthica from A. proteus when pseudopod formation started was greater for colonies than for single cells. Prey size did not affect the number of pseudopodia formed and the time between their formation, pulsatile kinematics and speed of extension by pseudopodia, or percent of prey lost by the predator. S. helianthica did not change swimming speed or execute escape maneuvers in response to being pursued by pseudopodia, so size‐selective feeding by A. proteus was due to predator behavior rather than prey escape. Our results do not support the theory that the selective advantage of becoming multicellular by choanoflagellate‐like ancestors of animals was reduced susceptibility to protozoan predation.
Potential virulence factors of Nocardia seriolae AHLQ20‐01 based on whole‐genome analysis and its pathogenicity to largemouth bass (Micropterus salmoides)
Authors: Cao Shoulin , Chang Jiaojiao , Yue Xiaozhen , Li Jinnian , Liu Xuelan 
Published: December 2022

AbstractNocardia seriolae is a major causative agent of fish nocardiosis that results in serious economic losses in the aquaculture industry. However, the virulence factors and pathogenic mechanisms of the bacterium are poorly understood. Here, a new N. seriolae strain AHLQ20‐01 was isolated from the diseased Micropterus salmoides and identified by phenotypic examination combined with 16S rRNA sequencing. Subsequently, the potential virulence factors of the strain were analysed at genome level by whole‐genome sequencing. The results showed that the whole‐genome sequence derived from N. seriolae AHLQ20‐01 circular chromosome contains 8,129,380 bp DNA with G + C content of 68.14%, and encompasses 7650 protein‐coding genes, 114 pseudo‐genes, 3 rRNAs, 66 tRNAs and 36 non‐coding RNAs. More importantly, a total of 139 genes, which mainly involved in adhesion, invasion, resistance to oxidative and nitrosative stress, phagosome arresting, iron acquisition system, toxin production and bacterial secretion systems, were identified as core virulence‐associated genes. Furthermore, the pathogenicity of N. seriolae AHLQ20‐01 to M. salmoides was further investigated through experimental infection. It was found that the LD50 value of the strain to M. salmoides was 9.3 × 106 colony forming unit/fish. Histopathological examination demonstrated typical granuloma with varying sizes in the liver, head kidney, spleen and heart of the experimentally infected fish. Terminal deoxynucleotidyl transferase dUTP nick end labelling assay and 4′,6‐diamidino‐2‐phenylindole staining showed that there were distinctly more apoptotic cells in all the tested tissues in the infection group, but not in the control group. Together, these findings provide the foundation to further explore the pathogenic mechanism of N. seriolae, which might contribute to the prevention and treatment of fish nocardiosis.