bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID‐19‐related social restrictions on orthopaedic trauma in a level 1 trauma centre in Sydney: the first wave
Authors: Probert Annabel C. , Sivakumar Brahman S. , An Vincent , Nicholls Sarah L. , Shatrov Jobe G. , Symes Michael J. , Ellis Andrew M. 
Published: October 2020

AbstractBackgroundThe coronavirus disease 2019 (COVID‐19) pandemic has affected communities worldwide. This study examines the impact that public health measures to control viral spread have had on orthopaedic trauma presenting to an Australian level 1 trauma centre. We hypothesized that the volume of orthopaedic trauma in the period of social distancing would decrease, and the mechanisms of injury differ, compared to pre‐pandemic times.MethodsWe performed a retrospective analysis of patients requiring emergency orthopaedic surgery between 16 March and 21 April 2020 (the period after social distancing and lockdown commenced), and compared it to the group of patients from the same period in 2019. We collected demographic data, as well as injury type, anatomical location, mechanism of injury and surgical logistics.ResultsDuring the COVID‐19 period, total emergency operations performed decreased by 15.6% compared to the same period in 2019. Orthopaedic admissions decreased by 30.8%. Demographics of the groups were unchanged. Anaesthetic time decreased, but total time spent in the operating theatre was unchanged. Road trauma comprised a similar proportion of cases overall; however, cycling‐related accidents increased significantly, making up 11% of presentations during COVID‐19. Sporting injuries, work‐related injuries and multi‐traumas reduced during the pandemic.ConclusionThe impact of COVID‐19‐related lockdown measures and social distancing on orthopaedic trauma in Australia has been an overall decrease in volume of cases, combined with significant changes in the mechanisms of injury necessitating surgery.
Human neutrophils swim and phagocytise bacteria
Authors: Garcia‐Seyda Nicolas , Seveau Valentine , Manca Fabio , Biarnes‐Pelicot Martine , Valignat Marie‐Pierre , Bajénoff Marc , Theodoly Olivier 
Published: October 2020

Background InformationLeukocytes migrate in an amoeboid fashion while patrolling our organism in the search for infection or tissue damage. Their capacity to migrate has been proven integrin independent, however, non‐specific adhesion or confinement remain a requisite in current models of cell migration. This idea has been challenged twice within the last decade with human neutrophils and effector T lymphocytes, which were shown to migrate in free suspension, a phenomenon termed swimming. While the relevance of leukocyte swimming in vivo remains under judgment, a growing amount of clinical evidence demonstrates that leukocytes are indeed found in liquid‐filled body cavities, occasionally with phagocyted pathogens, such as in the amniotic fluid, the cerebrospinal fluid (CSF), or the eye vitreous and aqueous humor.ResultsWe studied in vitro swimming of primary human neutrophils in the presence of live bacteria, in 2 and 3 dimensions. We show that swimming neutrophils perform phagocytosis of bacteria in suspension. By micropatterning live bacteria on a substrate with an optical technique, we further prove that they use chemotaxis to swim towards their targets. Moreover, we provide evidence that neutrophil navigation can alternate between adherent and non‐adherent modes.ConclusionsOur results suggest that human neutrophils do not rely on adhesion to carry out their functions, supporting a versatile phagocytic function adaptable to the various environmental conditions encountered in vivo, as already suggested by clinical data.SignificanceWe verified a claim stated 10 years ago and never reproduced, on the capacity of human neutrophils to swim and perform swimming chemotaxis. We further extended those results to prove that swimming neutrophils can phagocytise bacteria, disregarding adhesion nor confinement as a requisite for accomplishing their function, which differs with current paradigms of leukocyte migration.
Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma
Authors: Ye Dingwei , Liu Jiyan , Zhou Aiping , Zou Qing , Li Hanzhong , Fu Cheng , Hu Hailong , Huang Jian , Zhu Shaoxing , Jin Jie , Ma Lulin , Guo Jianming , Xiao Jun , Park Se Hoon , Zhang Dahong , Qiu Xiusong , Bao Yuanyuan , Zhang Lilin , Shen Wei , Bi Feng 
Published: October 2020

AbstractTislelizumab, an anti‐programmed death protein‐1 (PD‐1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody‐dependent phagocytosis, a mechanism of T‐cell clearance and potential resistance to anti‐PD‐1 therapy. This single‐arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD‐L1‐positive urothelial carcinoma who progressed during/following platinum‐containing therapy and had no prior PD‐(L)1 inhibitor treatment. Patients were considered PD‐L1 positive if ≥ 25% of tumor/immune cells expressed PD‐L1 when using the VENTANA™ PD‐L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow‐up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy‐evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression‐free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment‐related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3‐4 treatment‐related adverse events and occurred in ≥ 5% of patients. Three investigator‐assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD‐L1‐positive urothelial carcinoma and had a manageable safety profile.
Progesterone, via yes‐associated protein, promotes cardiomyocyte proliferation and cardiac repair
Authors: Lan Cong , Cao Nian , Chen Caiyu , Qu Shuang , Fan Chao , Luo Hao , Zeng Andi , Yu Cheng , Xue Yuanzheng , Ren Hongmei , Li Liangpeng , Wang Hongyong , Jose Pedro A. , Xu Zaicheng , Zeng Chunyu 
Published: October 2020

AbstractObjectivesThe mechanisms responsible for the postnatal loss of mammalian cardiac regenerative capacity are not fully elucidated. The aim of the present study is to investigate the role of progesterone in cardiac regeneration and explore underlying mechanism.Materials and MethodsEffect of progesterone on cardiomyocyte proliferation was analysed by immunofluorescent staining. RNA sequencing was performed to screen key target genes of progesterone, and yes‐associated protein (YAP) was knocked down to demonstrate its role in pro‐proliferative effect of progesterone. Effect of progesterone on activity of YAP promoter was measured by luciferase assay and interaction between progesterone receptor and YAP promoter by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Adult mice were subjected to myocardial infarction, and then, effects of progesterone on adult cardiac regeneration were analysed.ResultsProgesterone supplementation enhanced cardiomyocyte proliferation in a progesterone receptor‐dependent manner. Progesterone up‐regulated YAP expression and knockdown of YAP by small interfering RNA reduced progesterone‐mediated cardiomyocyte proliferative effect. Progesterone receptor interacted with the YAP promoter, determined by ChIP and EMSA; progesterone increased luciferase activity of YAP promoter and up‐regulated YAP target genes. Progesterone administration also promoted adult cardiomyocyte proliferation and improved cardiac function in myocardial infarction.ConclusionOur data uncover a role of circulating progesterone withdrawal as a novel mechanism for the postnatal loss of mammalian cardiac regenerative potential. Progesterone promotes both neonatal and adult cardiomyocyte proliferation by up‐regulating YAP expression.
Metaplastic spiradenocarcinoma: Report of two cases with sarcomatous differentiation
Authors: Held Laura , Ruetten Arno , Saggini Andrea , Kempter Wolfgang , Tiedke Carmen , Weber‐Kuhn Susanne , De Saint Aubain Nicolas , Mentzel Thomas 
Published: October 2020

AbstractSpiradenocarcinoma (SC) is a very rare malignant skin adnexal tumor with sweat gland differentiation that develops from a pre‐existing spiradenoma, cylindroma, or hybrid tumor called spiradenocylindroma, or arises de novo. We present two exceptionally rare SC cases showing sarcomatous differentiation; we also discuss the clinicopathologic features of SC, as well as its differential diagnoses and available therapeutic modalities. Given the aggressive behavior of SC, rapid diagnosis and complete removal of the tumor with tumor‐free margins is mandatory. Owing to the marked morphological heterogeneity of individual SC cases, dermatopathologists must be familiar with the different possible histopathologic manifestations of this neoplasm.
Landscape simplification increases vineyard pest outbreaks and insecticide use
Authors: Paredes Daniel , Rosenheim Jay A. , Chaplin‐Kramer Rebecca , Winter Silvia , Karp Daniel S. 
Published: October 2020

AbstractDiversifying agricultural landscapes may mitigate biodiversity declines and improve pest management. Yet landscapes are rarely managed to suppress pests, in part because researchers seldom measure key variables related to pest outbreaks and insecticides that drive management decisions. We used a 13‐year government database to analyse landscape effects on European grapevine moth (Lobesia botrana) outbreaks and insecticides across c. 400 Spanish vineyards. At harvest, we found pest outbreaks increased four‐fold in simplified, vineyard‐dominated landscapes compared to complex landscapes in which vineyards are surrounded by semi‐natural habitats. Similarly, insecticide applications doubled in vineyard‐dominated landscapes but declined in vineyards surrounded by shrubland. Importantly, pest population stochasticity would have masked these large effects if numbers of study sites and years were reduced to typical levels in landscape pest‐control studies. Our results suggest increasing landscape complexity may mitigate pest populations and insecticide applications. Habitat conservation represents an economically and environmentally sound approach for achieving sustainable grape production.
Distinct compartmentalization of immune cells and mediators characterizes bullous pemphigoid disease
Authors: Margaroli Camilla , Bradley Bridget , Thompson Cecilia , Brown Milton R. , Giacalone Vincent D. , Bhatt Lopa , Stoff Benjamin , Ahuja Sanjeev , Springman Eric , Tirouvanziam Rabindra , Feldman Ron J. 
Published: October 2020

AbstractBullous pemphigoid (BP) is an autoimmune blistering disease characterized by recruitment of leucocytes into skin and release of damaging enzymes, resulting in epidermal detachment and blister formation. To better understand the role of leukotriene B4 (LTB4) and other inflammatory factors in BP pathophysiology, we conducted microscopic and immunohistochemical analyses of preserved skin biopsy sections and conducted flow cytometry and ELISA analyses of matched blood and blister fluid from BP patients. Neutrophils predominated in BP blister fluid, which also contained monocytes/macrophages and T cells, but few to no eosinophils and B cells. In contrast, BP skin histology showed a different pattern, with abundant neutrophils but eosinophils being the predominant immune cell type. LTB4 pathway and neutrophil activation markers were prevalent in BP skin lesions and strongly associated with perivascular neutrophils. Blister fluid neutrophils, monocytes/macrophages and eosinophils all exhibited increased surface expression of leukotriene A4 hydrolase and neutrophil elastase (P = .002 for both). Blister fluid was also enriched in interleukins (IL)‐1α, IL‐1β, IL‐8, IL‐10, IL‐18, monocyte colony‐stimulating factor (M‐CSF) and vascular endothelial growth factor (VEGF). Our findings suggest differential leucocyte recruitment from blood into dermis and from dermis into blister, which correlates with disease activity, and presents potential new treatment opportunities for BP.
Correlation between the clinically diagnosed inflammatory process and periapical index scores in severely painful endodontically involved teeth
Authors: Rechenberg D. K. , Munir A. , Zehnder M. 
Published: October 2020

AbstractAimTo assess and correlate three distinct states of severely painful endodontically derived inflammation with their depiction on periapical radiographs using periapical index (PAI) scores.MethodologyDuring a period of 15 months, 368 consecutively enrolled patients with suspected endodontic emergency conditions were examined at the University of Zurich, Center of Dental Medicine. Cases with a severely painful (numeric rating scale, NRS‐11 > 6) endodontically involved tooth and a clear pulpal and apical diagnosis (n = 162) were selected (one tooth per patient). Teeth were divided into three groups according to the clinically diagnosed main location of the inflammatory process: level 1: pulp (positive response to cold test), level 2: periodontium (no response to cold without swelling) and level 3: periapical tissues (no response to cold with swelling). Periapical radiographs were obtained using a digital unit and analysed by two calibrated observers. For level 2, which had the highest PAI variance (n = 76), the PAI scores were further scrutinized regarding their dependence on tooth location and the duration of pain. Data were analysed using chi‐squared and non‐parametric tests, alpha = 0.05.ResultsOverall, the PAI scores correlated well with the clinically diagnosed main location of periapical inflammation (Spearman’s rho = 0.5131,P < 0.001), with level 1 having the lowest scores by far (P < 0.001) and level 2 having significantly lower scores compared to level 3 (P < 0.05). However, a PAI score of 5 was found in merely 3 teeth within the entire cohort, and 49% of the teeth in the level 2 group had no radiolucency (PAI < 3). Within level 2, the PAI scores were not dependent on tooth location but were substantially (P < 0.001) higher for teeth which had hurt for more than one week, and for root filled teeth.ConclusionsFor the analysed, severely painful endodontically involved teeth, the clinically diagnosed main location of inflammation was reflected by the periapical index. PAI scores were not significantly influenced by anatomical noise, yet in some cases under‐estimated the clinical situation.
Multidrug‐resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature
Authors: Fattahi Azam , Shirvani Fariba , Ayatollahi Azin , Rezaei‐Matehkolaei Ali , Badali Hamid , Lotfali Ensieh , Ghasemi Reza , Pourpak Zahra , Firooz Alireza 
Published: October 2020

AbstractBackgroundThe global spread of terbinafine‐resistant Trichophyton mentagrophytes with point mutations in the squalene epoxidase (SQLE) gene is a big concern.AimThe present study presents a series of unusual familial cases of generalized dermatophytosis caused by multidrug‐resistant T. mentagrophytes genotype VIII.MethodsInitially, the skin samples of each patient were taken and then subjected to direct microscopy and culture in Mycosel Agar. The molecular identification of Trichophyton species (spp.) was performed for all family members. In addition, the immunologic tests were requested, and an antifungal susceptibility test was carried out using the broth microdilution protocol based on the Clinical and Laboratory Standards Institute M38, third edition. The SQLE gene for a terbinafine‐resistant T. mentagrophytes genotype VIII was sequenced and confirmed its nucleotide sequence to KU242352 as a susceptible strain.ResultsBased on the results of mycological examination and ITS rDNA sequencing, the etiologic agent was identified as T. mentagrophytes as a zoophilic dermatophyte. This species showed multiple drug resistance in vitro against terbinafine (minimum inhibitory concentration (MICs ≥8 µg/ml), itraconazole (MIC ≥4), and fluconazole (MIC ≥16). The SQLE gene of the isolate was subjected to sequencing for mutation, which showed a point mutation as TTC/TTA in the gene leading to Phe397Leu amino acid substitution in the enzyme. Only one of the family members responded to itraconazole and was cured after the long‐term use of itraconazole. Other family members were treated with oral voriconazole with no recurrence.ConclusionThe transmission of this resistant T. mentagrophytes to other countries due to globalization is a serious issue to be considered.
Structural characterization and immunomodulatory activity of a new polysaccharide isolated from the radix of Platycodon grandiflorum
Authors: Shan Shan , Xiong Yi , Liu Mengyao , Zeng Deyong , Song Chen , Baranenko Denis , Cheng Dayou , Lu Weihong 
Published: October 2020

SummaryIn this study, a novel polysaccharide fraction (PGPIV‐1‐a) was isolated from Platycodon grandiflorum through the combination of DEAE‐52 and Sephadex G‐100 chromatography. PGPIV‐1‐a was a neutral heteropolysaccharide with an average molecular weight of about 6462 Da. PGPIV‐1‐a was composed of glucose, arabinose and mannose in the relative molar ratio of 64.79%, 31.16% and 4.05%. The main linkage types in PGPIV‐1‐a consisted of → 6)‐β‐Glcp‐(1 → and →5)‐α‐L‐Ara‐(1→. Bioactivity assay results showed that PGPIV‐1‐a significantly stimulated the proliferation of RAW264.7 cells and enhanced their phagocytic capacity in a dose‐dependent manner. In addition, treatment with higher dosage of PGPIV‐1‐a (800 μg mL−1) remarkably induced the secretion of NO, TNF‐α and IL‐6. This study provides a theoretical basis for further systematic investigation and utilisation of Platycodon grandiflorum polysaccharides.
“They just get it” an exploration of father's experiences and perceptions of a support group for men caring for children with disabilities and/or developmental delay
Authors: Batchelor Molly , Maguire Sabine , Shearn Julia 
Published: October 2020

AbstractBackgroundSupport groups available to parents/carers of children with a disability or developmental delay (DDD) are predominately attended by women. Limited data exists reporting experiences of the few male‐only support groups. This paper examines experiences of fathers of children with DDD attending a male‐only support group from South Wales.MethodAll fifteen members from a support group for fathers/male carers of children with DDD were invited to take part in qualitative interviews and seven participated. The data were analysed following Braun and Clarke's (Qualitative research in psychology, 2006, 3:77) thematic framework.ResultsWithin the group, fathers felt understood by similarly situated men, and a sense of connectivity and belonging. Fathers perceived exclusion elsewhere, including mixed‐gender groups. Fathers felt permission to talk in a way consistent with their male identities, and valued receiving, and giving, support.ConclusionsMixed‐gender support groups may not meet the needs of fathers, and there are potential benefits in providing male‐only groups.
Long non‐coding RNA MEG3 inhibits M2 macrophage polarization by activating TRAF6 via microRNA‐223 down‐regulation in viral myocarditis
Authors: Xue Yu‐Long , Zhang Sheng‐Xiao , Zheng Chao‐Feng , Li Yu‐Feng , Zhang Li‐Hui , Su Qin‐Yi , Hao Yu‐Fei , Wang Shu , Li Xue‐Wen 
Published: October 2020

AbstractViral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non‐coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor‐associated factor 6 (TRAF6) were silenced and microRNA‐223 (miR‐223) was over‐expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual‐luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR‐223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase‐1), M1 markers (CD86, iNOS and TNF‐α) and M2 markers (CD206, Arginase‐1 and Fizz‐1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR‐223 expression was significantly reduced. Down‐regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR‐223. TRAF6 was negatively correlated with miR‐223, but positively correlated with MEG3 expression. Down‐regulations of MEG3 or TRAF6 or up‐regulation of miR‐223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF‐κB pathway inactivation in VMC mice. Down‐regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up‐regulating miR‐223. Collectively, down‐regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR‐223/TRAF6/NF‐κB axis, thus alleviating VMC.
Association of hyperglycaemia with periodontal status: Results of the Northern Finland Birth Cohort 1966 study
Authors: Tegelberg Paula , Tervonen Tellervo , Knuuttila Matti , Jokelainen Jari , Keinänen‐Kiukaanniemi Sirkka , Auvinen Juha , Ylöstalo Pekka 
Published: October 2020

AbstractAimTo investigate the association of hyperglycaemia and changes in glycaemic control with periodontal status in non‐diabetic individuals.Materials and methodsA sub‐population (n = 647) of the Northern Finland Birth Cohort 1966 was studied. We categorized long‐term glucose balance based on fasting plasma glucose (FPG) at ages 31 and 46: FPG <5.0 mmol/l (strict normoglycaemia), FPG 5.0–5.59 mmol/l (slightly elevated FPG) and FPG 5.6–6.9 mmol/l (prediabetes). Probing pocket depth (PPD) and alveolar bone level (BL) data were collected at age 46. Relative risks (RR, 95% CI) were estimated using Poisson regression models.ResultsPeriodontal status was poorer in individuals whose glucose balance worsened from age 31 to 46 years than in those with a stable glucose balance. In the case of strict normoglycaemia at age 31 and slightly elevated FPG or prediabetes at age 46, the RRs for PPD ≥4 mm were 1.8 (95% CI 1.4–2.2) and 2.8 (95% CI 2.0–3.8) and for BL ≥5 mm 1.1 (95% CI 0.8–1.4) and 1.8 (95% CI 1.2–2.8), respectively.ConclusionThe results of this population‐based cohort study suggest that impairment in glucose control in non‐diabetic individuals is associated with periodontal pocketing and alveolar bone loss.
A need to consider the evolutionary genetics of host–symbiont mutualisms
Authors: Stoy Kayla S. , Gibson Amanda K. , Gerardo Nicole M. , Morran Levi T. 
Published: October 2020

AbstractDespite the ubiquity and importance of mutualistic interactions, we know little about the evolutionary genetics underlying their long‐term persistence. As in antagonistic interactions, mutualistic symbioses are characterized by substantial levels of phenotypic and genetic diversity. In contrast to antagonistic interactions, however, we, by and large, do not understand how this variation arises, how it is maintained, nor its implications for future evolutionary change. Currently, we rely on phenotypic models to address the persistence of mutualistic symbioses, but the success of an interaction almost certainly depends heavily on genetic interactions. In this review, we argue that evolutionary genetic models could provide a framework for understanding the causes and consequences of diversity and why selection may favour processes that maintain variation in mutualistic interactions.