bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whether preoperative hysteroscopy increases the dissemination of endometrial cancer cells: A systematic review and meta‐analysis
Authors: Dong He , Wang Yongxin , Zhang Mingyue , Sun Mengzi , Yue Ying 
Published: June 2021

AbstractAimTo determine whether hysteroscopy (HSC) increases the risk of intraperitoneal dissemination in endometrial cancer patients.MethodsWe conducted a comprehensive review of multiple databases. Quality assessments of eligible studies were performed using the Newcastle‐Ottawa and Jadad scales. Positive peritoneal cytology (PPC) as the outcome of interest was compared between endometrial cancer patients with and without HSC. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as a measure of effects.ResultsThree case–control studies and eight retrospective cohort studies included 3364 patients, of whom 1116 underwent preoperative HSC, which resulted in a significantly higher PPC rate (OR, 1.82; 95% CI, 1.31–2.54; p = 0.0004). I2 was 11%, and the heterogeneity was acceptable. The difference between the groups with stages I–II was statistically insignificant (OR, 1.50; 95% CI, 0.75–2.99; p = 0.25). When liquid was used as the uterine distension medium during HSC and the intrauterine pressure was controlled under 80 mmHg, the difference between the two groups was also insignificant (OR, 1.18; 95% CI, 0.50–2.79; p = 0.71). However, when the intrauterine pressure exceeded 80 mmHg, the difference between the two groups was statistically significant (OR, 2.18; 95% CI, 1.28–3.73; p = 0.004).ConclusionThis meta‐analysis indicates that preoperative HSC in patients with endometrial cancer may increase the risk of intraperitoneal dissemination of malignant cells, which may be associated with intrauterine pressure >80 mmHg but not with stages I–II. There is no reason to avoid HSC for the diagnosis of endometrial cancer, especially in early stages, but intrauterine pressure should possibly be controlled below 80 mmHg.
Challenges facing pathologists evaluating PD‐L1 in head & neck squamous cell carcinoma
Authors: Girolami Ilaria , Pantanowitz Liron , Barberis Massimo , Paolino Gaetano , Brunelli Matteo , Vigliar Elena , Munari Enrico , Satturwar Swati , Troncone Giancarlo , Eccher Albino 
Published: June 2021

AbstractBackgroundProgrammed death‐ligand 1 (PD‐L1) expression with combined positive score (CPS) ≥1 is required for administration of checkpoint inhibitor therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The 22C3 pharmDx Dako immunohistochemical assay is the one approved as companion diagnostic for pembrolizumab, but many laboratories work on other platforms and/or with other clones, and studies exploring the potential interchangeability of assays have appeared.Evidence from the literatureAfter review of the literature, it emerges that the concordance among assays ranges from fair to moderate, with a tendence of assay SP263 to yield a higher quota of positivity and of assay SP142 to stain better immune cells. Moreover, pathologists achieve very good concordance in assessing PD‐L1 CPS, particularly with SP263.ConclusionsDifferences in terms of platforms, procedures, and study design still preclude a quantitative synthesis of evidence and clearly further work is needed to draw stronger conclusions on the interchangeability of PD‐L1 assays in HNSCC.
Genetic background of lumbosacral transitional vertebrae in German shepherd dogs
Authors: Gluding D. , Stock K. F. , Tellhelm B. , Kramer M. , Eley N. 
Published: June 2021

ObjectivesEstimation of genetic parameters of lumbosacral transitional vertebrae based on data derived from radiographic screening of 27,597 German shepherd dogs.Materials and MethodsResults of radiographic screening for lumbosacral transitional vertebrae classified according to a published scheme were collected. Obtained data were used for estimating variance components in single and multiple trait linear animal models to obtain heritabilities and additive genetic correlations for different types of lumbosacral transitional vertebrae.ResultsEstimations indicated a moderate heritability of lumbosacral transitional vertebrae of h2 = 0.27. Trait definitions reflecting the different types of lumbosacral transitional vertebrae revealed positive additive genetic correlations of rg > 0.5 between those types usually categorised as pathologic.Clinical SignificanceResults of comprehensive genetic analyses enable the development of breeding measures against lumbosacral transitional vertebrae to reduce their prevalence and support management of potentially correlated diseases in German shepherd dogs.
New therapies for hepatitis delta virus infection
Authors: Loureiro Dimitri , Castelnau Corinne , Tout Issam , Boyer Nathalie , Narguet Stéphanie , Menasria Benazzouz Sabrina , Louis Zeina , Pons‐Kerjean Nathalie , Giuly Nathalie , Marcellin Patrick , Mansouri Abdellah , Asselah Tarik 
Published: June 2021

AbstractHepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. HDV infection remains endemic in several regions including Central and West Africa, the Mediterranean basin, the Middle East, Eastern Europe, Northern Asia, certain areas of Southeast Asia and the Amazon basin of South America. The best preventive strategy to decrease HDV infection is to improve coverage of the prophylactic HBV vaccine. HDV infection may occur by HBV‐HDV co‐infection or superinfection, and the latter is usually more severe. CHD is associated with a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to HBV mono‐infection. Pegylated interferon alpha (PEG‐IFNα) therapy is limited by moderate effectiveness (around 20%) and its adverse effects. The entry inhibitor, bulevirtide (BLV, Hepcludex®), which was recently approved in Europe at a dose of 2 mg in sub‐cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG‐IFNα. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFNλ) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release). In this review, we will present an update on CHD and future promising treatments.
Non‐alcoholic fatty liver disease in type 2 diabetes – A specific entity?
Authors: Schröder Benjamin , Kahl Sabine , Roden Michael 
Published: June 2021

AbstractIndividuals with obesity or type 2 diabetes (T2D) have an increased risk of developing non‐alcoholic fatty liver disease (NAFLD). In insulin‐resistant states, altered adipose tissue function may be the initial abnormality underlying NAFLD. Hepatic lipid oversupply interferes with insulin signalling and mitochondrial function. In obese individuals, adaptation of hepatic mitochondrial respiration fails with the progression of NAFLD and can activate pro‐inflammatory pathways. T2D as well as type 1 diabetes are associated with altered hepatic mitochondrial function. Screening for NAFLD remains challenging especially in those with diabetes because liver enzymes are often in the normal range and the performance of NAFLD scores is limited. Patients with T2D and severe insulin‐resistant diabetes (SIRD) have the highest prevalence of NAFLD at diagnosis and the greatest risk of progression. In this subgroup, the single‐nucleotide‐polymorphism (SNP) rs738409(G) of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene is associated with high liver fat content and adipose tissue insulin resistance. This frequent SNP is also known to be associated with lean NAFLD so that genetic testing for this and other SNPs could improve future screening strategies to identify high‐risk individuals. Although lifestyle modifications are effective, this approach is limited owing to difficulties with compliance and several classes of drugs are being tested to treat NAFLD. Antihyperglycaemic drugs such as glucagon‐like peptide 1 receptor agonists (GLP‐1 RA), sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and pioglitazone are promising and halt the progression of NAFLD. In conclusion, although NAFLD in diabetes may not be a separate entity, there are specific features to its pathogenesis and clinical management.
HBV 2021: New therapeutic strategies against an old foe
Authors: Roca Suarez Armando Andres , Testoni Barbara , Zoulim Fabien 
Published: June 2021

AbstractHepatitis B virus (HBV) affects more than 250 million people worldwide, and is one of the major aetiologies for the development of cirrhosis and hepatocellular carcinoma (HCC). In spite of universal vaccination programs, HBV infection is still a public health problem, and the limited number of available therapeutic approaches complicates the clinical management of these patients. Thus, HBV infection remains an unmet medical need that requires a continuous effort to develop new individual molecules, treatment combinations and even completely novel therapeutic strategies to achieve the goal of HBV elimination. The following review provides an overview of the current situation in chronic HBV infection, with an analysis of the scientific rationale of certain clinical interventions and, more importantly, explores the most recent developments in the field of HBV drug discovery.
End‐stage liver disease: Management of hepatorenal syndrome
Authors: Mauro Ezequiel , Garcia‐Olveira Lucrecia , Gadano Adrián 
Published: June 2021

AbstractHepatorenal syndrome (HRS) is a serious complication of cirrhosis with high morbidity and mortality rates. Recently, the definition of HRS type 1 has been updated and is now called HRS‐AKI. This new definition reduces the risk of delaying HRS treatment and eliminates the need to establish a minimum creatinine cut‐off for the diagnosis of HRS‐AKI. From a pathophysiological point of view, newly identified mechanisms involved in the development of HRS are related to the inflammatory response, conditioning the development of extrahepatic organ dysfunction in patients with cirrhosis. One of the main challenges for the diagnosis of HRS is the validation of new biomarkers to obtain an early and differential diagnosis of kidney injury (eg HRS vs. ATN). Treatment of HRS is based on the use of vasoconstrictive agents in combination with albumin and terlipressin is the most widely used vasoconstrictor drug, with a high response rate. The effects of a continuous infusion of terlipressin at a dose of 2‐12 mg/day was similar to bolus administration, but with lower rates of adverse events. Finally, MELD/MELD‐Na which includes creatinine as one of its main determinants gives AKI‐HRS patients priority on the waiting list (WL) for liver transplant (LT). However, the MELD and MELD‐Na scores are reduced in responding patients, resulting a longer waiting time in these patients than in non‐responders. Thus, the initial MELD/MELD‐Na score (pre‐treatment value) should be used to prioritize patients on the WL for LT in these cases.
Current management of NAFLD/NASH
Authors: Cardoso Ana Carolina , de Figueiredo‐Mendes Claudio , A. Villela‐Nogueira Cristiane 
Published: June 2021

AbstractNAFLD is the most common cause of liver disease worldwide, and its prevalence is significantly increasing. Studies have shown that it is associated with comorbidities such as diabetes, metabolic syndrome and obesity. Early diagnosis and management are highly important and could modify the prognosis of the disease. Evaluating the possibility of multiple aetiologies and recognizing the additional causes of liver disease should be a part of the patient's initial assessment. There are no approved drug treatments as yet, so the main management strategies should involve lifestyle changes such as physical activity and dietary re‐education.
A Phytophthora capsici RXLR effector targets and inhibits the central immune kinases to suppress plant immunity
Authors: Liang Xiangxiu , Bao Yazhou , Zhang Meixiang , Du Dandan , Rao Shaofei , Li Yixin , Wang Xiaodan , Xu Guangyuan , Zhou Zhaoyang , Shen Danyu , Chang Qin , Duan Weiwei , Ai Gan , Lu Jie , Zhou Jian‐Min , Dou Daolong 
Published: June 2021

Summary

Receptor‐like cytoplasmic kinase subfamily VII (RLCK‐VII) proteins are the central immune kinases in plant pattern‐recognition receptor (PRR) complexes, and they orchestrate a complex array of defense responses against bacterial and fungal pathogens. However, the role of RLCK‐VII in plant–oomycete pathogen interactions has not been established. Phytophthora capsici is a notorious oomycete pathogen that infects many agriculturally important vegetables.

Here, we report the identification of RXLR25, an RXLR effector that is required for the virulence of P. capsici. In planta expression of RXLR25 significantly enhanced plants’ susceptibility to Phytophthora pathogens. Microbial pattern‐induced immune activation in Arabidopsis was severely impaired by RXLR25. We further showed that RXLR25 interacts with RLCK‐VII proteins.

Using nine rlck‐vii high‐order mutants, we observed that RLCK‐VII‐6 and RLCK‐VII‐8 members are required for resistance to P. capsici. The RLCK‐VII‐6 members are specifically required for Phytophthora culture filtrate (CF)‐induced immune responses. RXLR25 directly targets RLCK‐VII proteins such as BIK1, PBL8, and PBL17 and inhibits pattern‐induced phosphorylation of RLCK‐VIIs to suppress downstream immune responses.

This study identified a key virulence factor for P. capsici, and the results revealed the importance of RLCK‐VII proteins in plant–oomycete interactions.
A rare cause of platypnea‐orthodeoxia syndrome in a young female due to persistent left superior vena cava
Authors: de Jesus Mikhail , Patel Nirav , Cheema Mohiuddin , Weissler‐Snir Adaya 
Published: June 2021

AbstractPlatypnea‐Orthodeoxia syndrome (POS) is a rare clinical syndrome characterized by shortness of breath in the upright position that is relieved with supine positioning. We present a rare case of persistent left superior vena cava (PLSVC) draining into the left atrium causing a right‐to‐left shunt and subsequent POS. A 30‐year‐old female with a past medical history of hypertrophic cardiomyopathy, congenital Long QT syndrome and a left‐sided dual chamber implantable cardioverter‐defibrillator (ICD) presented with dyspnea and lightheadedness. Prior to presentation, the patient underwent a left‐sided ICD extraction due to ICD lead infection and re‐implantation from the right side through the cephalic vein. After further investigation, it was concluded that the PLSVC resulted in a physiological right‐to‐left shunting causing POS, with resolution of her symptoms after surgical ligation. To our knowledge, this is the first case report of PLSVC presenting with POS without anatomical intracardiac shunts following iatrogenic right superior vena cava (RSVC) obstruction.
Cohort profile: The COPENHAGEN Minipuberty Study—A longitudinal prospective cohort of healthy full‐term infants and their parents
Authors: Busch Alexander Siegfried , Ljubicic Marie Lindhardt , Upners Emmie N. , Fischer Margit Bistrup , Kolby Nanna , Eckert‐Lind Camilla , Jespersen Kirstine , Andersson Anna‐Maria , Frederiksen Hanne , Johannsen Trine Holm , Hegaard Hanne Kristine , Sharif Heidi , Hagen Casper P. , Juul Anders 
Published: June 2021

AbstractBackgroundThe hypothalamic‐pituitary‐gonadal (HPG) axis governs sexual maturation and reproductive function in humans. In early postnatal life, it is transiently active during which circulating sex steroids reach adult levels. While this so‐called minipuberty represents a universal phenomenon in infants of both sexes, its role for early maturation and growth remains incompletely understood.ObjectivesTo provide normative data on auxology as well as serum and urinary hormone levels in healthy, full‐term infants throughout the first year of life and to investigate associations of postnatal HPG axis dynamics as well as hormonal, genetic and environmental exposures with early genital development and growth.PopulationHealthy, Danish, full‐term, singleton newborns including their parents.DesignSingle‐centre, prospective, observational longitudinal pregnancy and birth cohort.MethodsNewborns were followed with six repeated clinical examinations during a one‐year follow‐up period. An umbilical cord blood sample was drawn at birth. At each visit, infants underwent a clinical examination focusing on auxology and genital development. Further, blood (serum, plasma, DNA) and urine samples were collected at each visit. Mothers and fathers underwent a clinical examination and provided blood samples prior to and after birth. A subset of parents provided urine samples and breast milk samples. Pregnancy and obstetrical outcomes, and detailed parental questionnaires were compiled.Preliminary resultsBetween August 2016 and August 2018, 2481 women with singleton pregnancies were invited to participate of which 298, including their partners, were enrolled (12.0%). A total of 268 healthy, full‐term newborns born appropriate for gestational age (AGA) were included at birth, 233 newborns participated in the postnatal follow‐up period and 186 completed the one‐year follow‐up period (9.4% and 7.5%, respectively).ConclusionThe COPENHAGEN Minipuberty Study provides detailed, longitudinal data on early genital development and growth including hormonal and genetic profiles and environmental exposure in healthy infants including additional data in their parents.
Relatives’ negotiation power in relation to older people’s acute hospital admission: A qualitative interview study
Authors: Hoffmann Eva , Andersen Pernille Tanggaard , Mogensen Christian Backer , Prinds Christina , Primdahl Jette 
Published: June 2021

AbstractBackgroundAcutely admitted older people are potentially vulnerable and dependent on relatives to negotiate and navigate on their behalf.AimThis study aimed to explore relatives’ experiences of their interactions with healthcare professionals during acute hospital admission of older people to derive themes of importance for relatives’ negotiations with these professionals.MethodA qualitative design was applied. Relatives of acutely admitted older people at two emergency departments in Denmark were interviewed (n = 17). The qualitative content analysis was guided by Graneheim and Lundman's concepts.ResultsThe analysis derived four themes: (a) Mandate, (b) Incentive, (c) Capability and (d) Attitude to taking action. These four sources of relatives’ negotiation power can be illustrated in the MICA model.ConclusionFour themes were identified as important sources of relatives’ negotiation power. Since the four sources of power potentially change according to the situation, relatives’ negotiation power seems to be context dependent.
Agreeableness, extraversion and life satisfaction: Investigating the mediating roles of social inclusion and status
Authors: Fors Connolly Filip , Johansson Sevä Ingemar 
Published: June 2021

We examine inclusion and status as potential mediators in the relationships between extraversion and agreeableness, on the one hand, and life satisfaction, on the other hand. Previous research has shown that agreeableness is less strongly related to life satisfaction compared to extraversion. We argue that the relatively weak association between agreeableness and life satisfaction is due to the fact that, even though this personality trait is positively related to inclusion, it is only weakly related to status. Using structural equation modeling (SEM) and survey data from Australia, Denmark and Sweden, we test five hypotheses about the linkages between these personality traits, inclusion, status and life satisfaction. Our results show that both extraversion and agreeableness are positively associated with life satisfaction and that this association is much stronger for extraversion. Furthermore, our results show that extraversion is reliably associated with both inclusion and status, whereas agreeableness is a reliable predictor of inclusion but not of status. Turning to our mediation analysis, our main results demonstrate that the relationship between extraversion and life satisfaction is fully mediated by both inclusion and status, whereas the relationship between agreeableness and life satisfaction is partially mediated by inclusion. Our mediation analysis further shows that agreeableness has a negative direct effect on life satisfaction over and above the positive indirect effect through inclusion. Our findings highlight the role of both inclusion and status as important mediators in the relationships between extraversion and agreeableness, on the one hand, and life satisfaction, on the other hand.
Improving Lasso for model selection and prediction
Authors: Pokarowski Piotr , Rejchel Wojciech , Sołtys Agnieszka , Frej Michał , Mielniczuk Jan 
Published: June 2021

AbstractIt is known that the Thresholded Lasso (TL), SCAD or MCP correct intrinsic estimation bias of the Lasso. In this paper we propose an alternative method of improving the Lasso for predictive models with general convex loss functions which encompass normal linear models, logistic regression, quantile regression, or support vector machines. For a given penalty we order the absolute values of the Lasso nonzero coefficients and then select the final model from a small nested family by the Generalized Information Criterion. We derive exponential upper bounds on the selection error of the method. These results confirm that, at least for normal linear models, our algorithm seems to be the benchmark for the theory of model selection as it is constructive, computationally efficient and leads to consistent model selection under weak assumptions. Constructivity of the algorithm means that, in contrast to the TL, SCAD or MCP, consistent selection does not rely on the unknown parameters as the cone invertibility factor. Instead, our algorithm only needs the sample size, the number of predictors and an upper bound on the noise parameter. We show in numerical experiments on synthetic and real‐world datasets that an implementation of our algorithm is more accurate than implementations of studied concave regularizations. Our procedure is included in the R package DMRnet and available in the CRAN repository.