bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of chronological age on efficacy of immune checkpoint inhibitors in non‐small‐cell lung cancer: Real‐world data from 86 173 patients
Authors: Takamori Shinkichi , Shimokawa Mototsugu , Komiya Takefumi 
Published: October 2021

AbstractImmune checkpoint inhibitors (ICIs) have become standard pharmacological therapies in patients with non‐small‐cell lung cancer (NSCLC). Because elderly patients with NSCLC are often excluded from clinical trials as a result of lower functional capacity or comorbidities, the prognostic impact of chronological age on the efficacy of ICIs is unclear. The National Cancer Database was queried for stage IV NSCLC patients between 2014 and 2015. Associations between ICI therapy and clinical characteristics were assessed using chi‐squared tests. Kaplan–Meier curves were compared using the log‐rank test. A Cox proportional hazards model was used to identify clinical characteristics predictive of overall survival (OS). This study included 24 136 patients with stage IV NSCLC aged ≥75 years and 62 037 patients with stage IV NSCLC aged <75 years. Patients aged ≥75 years treated with ICIs had significantly longer OS than those not treated with ICIs (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.58–0.64, p < 0.0001). The corresponding HR in patients aged <75 years was 0.67 (95% CI 0.65–0.68, p < 0.0001). Cox modeling confirmed the survival benefit of ICI therapy in patients aged ≥75 years (HR for patients not receiving ICIs 1.63 [95% CI: 1.55–1.71], p < 0.0001). The corresponding HR in patients aged <75 years was 1.47 (95% CI 1.43–1.51, p < 0.0001). Chronological age does not appear to negatively impact the survival benefit of ICI therapy in patients with stage IV NSCLC according to this large real‐world database analysis.
Genetic liability for substance use associated with medical comorbidities in electronic health records of African‐ and European‐ancestry individuals
Authors: Hartwell Emily E. , Merikangas Alison K. , Verma Shefali S. , Ritchie Marylyn D. ,   Regeneron Genetics Center, Kranzler Henry R. , Kember Rachel L. 
Published: October 2021

AbstractPolygenic risk scores (PRS) represent an individual's summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record‐based biobanks makes it possible to evaluate the association of SUD PRS with other traits. We calculated PRS for smoking initiation, alcohol use disorder (AUD), and opioid use disorder (OUD) using summary statistics from the Million Veteran Program sample. We then tested the association of each PRS with its primary phenotype in the Penn Medicine BioBank (PMBB) using all available genotyped participants of African or European ancestry (AFR and EUR, respectively) (N = 18,612). Finally, we conducted phenome‐wide association analyses (PheWAS) separately by ancestry and sex to test for associations across disease categories. Tobacco use disorder was the most common SUD in the PMBB, followed by AUD and OUD, consistent with the population prevalence of these disorders. All PRS were associated with their primary phenotype in both ancestry groups. PheWAS results yielded cross‐trait associations across multiple domains, including psychiatric disorders and medical conditions. SUD PRS were associated with their primary phenotypes; however, they are not yet predictive enough to be useful diagnostically. The cross‐trait associations of the SUD PRS are indicative of a broader genetic liability. Future work should extend findings to additional population groups and for other substances of abuse.
A retrospective case series on transvaginal repair of rectovaginal fistula performed by a urogynaecology operative team in Australia
Authors: Thayalan Krishanthy , Krause Hannah , Goh Judith 
Published: October 2021

BackgroundRectovaginal fistula (RVF) is an abnormal epithelialised connection between the rectum and vagina. It is a common condition in limited resource settings and is caused almost exclusively by obstetric injury. In contrast, RVF is uncommonly seen in high resource settings.AimsThis study aims to review the aetiology and effectiveness of RVF management in the high resource setting, identifying predictors for repair success and long‐term outcomes.Materials and MethodsA retrospective case series study of patients who underwent transvaginal RVF repairs at two secondary healthcare facilities over a 14‐year period by one operative group.ResultsA total of 41 patients underwent 46 surgical repairs. All patients presented with flatal and/or faecal incontinence and aetiology was identifiable in 78.0% (n = 32). Obstetric cause was implicated in 26.8% (n = 11) and other causes include 26.8% (n = 11) from vaginal and abdominal surgery, 14.6% (n = 6) from perianal abscess, 7.32% (n = 3) as complications of Crohn’s disease and 2.44% (n = 1) as a complication of a cube pessary. Fistula was cured in 38 of 41 cases (92.7%) with a primary repair closure rate of 80.5% (n = 33). Post‐operative symptoms were limited to flatal incontinence in 4.88% (n = 2), faecal incontinence in 2.44% (n = 1), and persistent perineal pain in 7.32% (n = 3). The success of the surgical repair was not significantly impacted by fistula size, aetiology, presence of a stoma for diversion, history of prior repair, duration since RVF formation or repair technique.ConclusionsThis review identifies aetiology for RVF in the high resource setting and highlights the role of earlier surgical repair to minimise patient morbidity with good success in closure and reduction of post‐operative symptoms.
Providing children with COVID‐19 vaccinations is challenging due to lack of data and wide‐ranging parental acceptance
Authors: She Jiatong , Liu lanqin , Liu Wenjun 
Published: October 2021

AbstractAimVaccines are vital to ending the COVID‐19 pandemic and we reviewed the data on vaccinating children, and including them in clinical trials, as most of the activity has focused on adults.MethodsEnglish and Chinese databases, including PubMed, Elsevier Scopus, Web of Science, CNKI and CQVIP were searched, along with websites such as the World Health Organization and the University of Oxford.ResultsWe identified 44 papers and 16 news items about vaccinating children against the virus, published from 10 February 2020 to 14 July 2021. Child vaccination has been slow and only a few countries have included children in Phase II or III clinical trials. The data on children were much more limited than on adults, but most children were asymptomatic or had mild symptoms and some deaths had been recorded. More clinical trials are needed to assess the safety and efficacy of vaccinating children, as higher vaccination levels can help to build up herd immunity. The percentage of parents willing to vaccinate their children against the virus ranged from 48.2% to 72.6%, with much lower rates for letting them participate in clinical trials.ConclusionVaccines should be offered to children as soon as their safety and efficacy are established.
Drivers of depositor discipline in credit unions
Authors: Gómez‐Biscarri Javier , López‐Espinosa Germán , Mesa‐Toro Andrés 
Published: October 2021

AbstractIn this paper, we analyze whether credit unions are subject to market discipline by their (member) depositors and examine the drivers of such discipline. We first provide descriptive evidence of depositor discipline in credit unions: shares and deposits as well as savings interest rates react to variables that reflect the financial health of the credit union and its asset risk. We show that this discipline is long‐lasting and that it is mediated by the existence of a deposit guarantee scheme and by the strength of the relationship of members with the credit union. We then use proxies of the capability of members to process financial information to show that discipline is heavily influenced by member financial sophistication. Our results suggest that a type of market‐based discipline acts as a complement for regulation in controlling credit union risk taking, thus contributing to overall financial stability.
Temporal stability in species richness but reordering in species abundances within avian assemblages of a tropical Andes conservation hot spot
Authors: Tinoco Boris A. , Latta Steven C. , Astudillo Pedro X. , Nieto Andrea , Graham Catherine H. 
Published: October 2021

AbstractAs the pace of environmental change increases, there is an urgent need for quantitative data revealing the temporal dynamics of local communities in tropical areas. Here, we quantify the stability of avian assemblages in the highly threatened, but poorly studied, Andean biodiversity hot spot. We evaluated the temporal variation in species richness and community composition of local bird assemblages in three habitat types (native forest, introduced forest, native shrub) using a unique, relatively long‐term data series from Cajas National Park and Mazán Reserve in the southern Andes of Ecuador. We sampled birds with mist nets using a standardized protocol over 11 years, from 2006 to 2016. Species richness remained stable over time across habitats, but community composition changed in the native forest. In particular, we observed taxonomic reordering in the native forest, in which the evenness in the distribution of abundances of taxa decreased over time. This finding is consistent with other studies where species richness remained constant over time while community composition changed. Our study highlights the value of long‐term studies in the tropical Andes as we show that species composition of birds in a montane forest is changing, consistent with global trends in biodiversity change.Abstract in Spanish is available with online material.
Long‐term health outcomes in young women with polycystic ovary syndrome: A narrative review
Authors: Allen Lowri A. , Shrikrishnapalasuriyar Natasha , Rees Dafydd Aled 
Published: October 2021

AbstractPolycystic ovary syndrome (PCOS) has long been recognized as a common disorder in young women leading to reproductive and cutaneous sequelae. However, the associated health risks are now known to extend beyond these familiar manifestations to a range of longer‐term comorbidities. Here we review the evidence for an association of PCOS with adverse long‐term health outcomes, discussing the pathophysiological mechanisms involved in addition to opportunities for therapeutic intervention. Cross‐sectional and longitudinal studies point to an increased risk of type 2 diabetes, hypertension and dyslipidaemia, with recent data confirming that these translate to an increased risk of cardiovascular events independently of obesity. Obstructive sleep apnoea, nonalcoholic fatty liver disease and endometrial cancer are also more prevalent, while mental health disorders, notably anxiety and depression, are common but under‐appreciated associations. Uncertainties remain as to whether these risks are apparent in all patients with PCOS or are confined to particular subtypes, whether risks persist post‐menopausally and how risk may be affected by ethnicity. Further work is also needed in establishing if systematic screening and targeted intervention can lead to improved outcomes. Until such data are available, clinicians managing women with PCOS should counsel patients on long‐term health risks and invest in strategies that limit progression to metabolic and non‐metabolic morbidities.
Runx3 regulates iron metabolism via modulation of BMP signalling
Authors: Kim Hyun‐Yi , Lee Jong‐Min , Lee You‐Soub , Li Shujin , Lee Seung‐Jun , Bae Suk‐Chul , Jung Han‐Sung 
Published: October 2021

AbstractObjectivesRunx3, a member of the Runx family of transcription factors, has been studied as a tumour suppressor and key player of organ development. In a previous study, we reported differentiation failure and excessive angiogenesis in the liver of Runx3 knock‐out (KO) mice. Here, we examined a function of the Runx3 in liver, especially in iron metabolism.MethodsWe performed histological and immunohistological analyses of the Runx3 KO mouse liver. RNA‐sequencing analyses were performed on primary hepatocytes isolated from Runx3 conditional KO (cKO) mice. The effect of Runx3 knock‐down (KD) was also investigated using siRNA‐mediated KD in functional human hepatocytes and human hepatocellular carcinoma cells.ResultWe observed an iron‐overloaded liver with decreased expression of hepcidin in Runx3 KO mice. Expression of BMP6, a regulator of hepcidin transcription, and activity of the BMP pathway were decreased in the liver tissue of Runx3 KO mice. Transcriptome analysis on primary hepatocytes isolated from Runx3 cKO mice also revealed that iron‐induced increase in BMP6 was mediated by Runx3. Similar results were observed in Runx3 knock‐down experiments using HepaRG cells and HepG2 cells. Finally, we showed that Runx3 enhanced the activity of the BMP6 promoter by responding to iron stimuli in the hepatocytes.ConclusionIn conclusion, we suggest that Runx3 plays important roles in iron metabolism of the liver through regulation of BMP signalling.
Histopathologic features of inverse psoriasis
Authors: Knabel Michael , Mudaliar Kumaran 
Published: October 2021

AbstractBackgroundInverse psoriasis represents a less commonly described form of psoriasis in intertriginous areas. The pathologic findings of inverse psoriasis are typically grouped in with those of plaque psoriasis, as the histopathologic features specific to inverse psoriasis have not received significant investigation.MethodsA single institution, retrospective cohort study was performed to review biopsy slides for psoriasis occurring in typical intertriginous areas. Patient's charts were reviewed and only those where the clinical diagnosis of inverse psoriasis was also favored were included.ResultsTwelve patients met inclusion criteria: 58% male and 42% female, 18 to 86 years of age. Classic features of psoriasis such as hypogranulosis, confluent parakeratosis, and thinning of the suprapapillary plate were seen in 100%. Regular psoriasiform acanthosis and dilated tortuous dermal vessels were seen in 92%. Neutrophils were present in the scale in 83% and in the dermis in 100%. Features considered atypical for psoriasis included spongiosis in 83%, eosinophils in 67%, and focal serum in the scale in 42%.ConclusionsWhile inverse psoriasis commonly exhibits features considered to be classic for psoriasis, it is not unusual for inverse psoriasis to show features considered atypical for plaque psoriasis such as dermal eosinophils, epidermal spongiosis, and focal serum in the scale.
Next‐generation sequencing confirms T‐cell clonality in a subset of pediatric pityriasis lichenoides
Authors: Raghavan Shyam S. , Wang Jennifer Y. , Gru Alejandro A. , Marqueling Ann L. , Teng Joyce M.C. , Brown Ryanne A. , Novoa Roberto A. , Kim Youn , Zehnder James , Zhang Bing Melody , Rieger Kerri E. 
Published: October 2021

AbstractBackgroundPityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T‐cell populations via PCR‐based assays. In this study, we sought to implement next‐generation sequencing (NGS) as a more sensitive and specific test to examine for T‐cell clonality within the pediatric population.MethodsWe identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T‐cell receptor beta (TRB) and gamma (TRG) genes.ResultsOf the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow‐up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T‐cell clonality. Two patients showed matching TRB clones from different anatomic sites.ConclusionsT‐cell clonality is a common finding in PL, probably representing a “reactive clonality” rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma.
Cutaneous reactive angiomatosis associated with intravascular cryoprotein deposition as the presenting finding in a patient with underlying lymphoplasmacytic lymphoma: A case report and review of the literature
Authors: Zacher Natasha C. , Bailey Elizabeth E. , Kwong Bernice Y. , Rieger Kerri E. 
Published: October 2021

AbstractCutaneous reactive angiomatosis, a group of disorders defined by benign vascular proliferation, is associated with a number of systemic processes, including intravascular occlusion by cryoproteins. We report a case of a 64‐year‐old female patient who presented with a 1‐year history of nontender petechiae of the bilateral arms and lower legs. Dermoscopic evaluation showed increased vascularity with a globular pattern. Over a period of months, her findings progressed to erythematous to violaceous plaques with admixed hypopigmented stellate scarring of the bilateral lower extremities, forearms, and lateral neck. Biopsy showed increased thin‐walled, small dermal blood vessels with focal inter‐anastamosis. Some vessels were occluded by eosinophilic globules suspicious for cryoprotein. Subsequent laboratory studies confirmed a diagnosis of type 1 cryoglobulinemia, prompting a bone marrow biopsy that revealed lymphoplasmacytic lymphoma. Herein, we report the fourth case of angiomatosis secondary to intravascular cryoproteins as the initial presentation of an underlying hematologic malignancy. We also present a review of the literature and emphasize the need for thorough initial workup and close and prolonged clinical monitoring for underlying systemic disease in these patients.
Muscle synergy structure and gait patterns in children with spastic cerebral palsy
Authors: Goudriaan Marije , Papageorgiou Eirini , Shuman Benjamin R , Steele Katherine M , Dominici Nadia , Van Campenhout Anja , Ortibus Els , Molenaers Guy , Desloovere Kaat 
Published: October 2021

AimTo determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP).MethodIn this cross‐sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo–17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non‐negative matrix factorization. We compared synergy activations and weights between the patterns.ResultsSynergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high.InterpretationThe similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.
Persistence of islet autoantibodies after diagnosis in type 1 diabetes
Authors: Long Anna E. , George Gifty , Williams Claire L. 
Published: October 2021

AbstractThe presence of islet autoantibodies remains a reliable biomarker to identify individuals at high risk of developing type 1 diabetes. As such, these autoantibodies play a pivotal role in understanding the prodrome of diabetes and selecting individuals for both prevention and intervention clinical trials. Over the last few decades, studies have sought to investigate autoantibody prevalence after diabetes onset to better understand ongoing islet autoimmunity; however, many findings are contradictory, and little is known about factors that may influence autoantibody persistence. Generally, glutamate decarboxylase autoantibodies (GADAs) are the most prevalent autoantibodies after diagnosis, particularly in adults, whilst zinc transporter 8 autoantibodies (ZnT8A) prevalence declines more rapidly. However, when studies with islet autoantibody data at diagnosis are considered, it becomes clear that overall islet antigen‐2 autoantibodies (IA‐2A) tend to persist for longer than GADA or ZnT8A. In this review, we assess the major studies that have contributed to our understanding of autoantibody persistence after diabetes onset and what factors affect this. Islet autoantibodies may provide biomarkers for long‐term β‐cell function and insights into how to prevent ongoing islet autoimmunity but larger studies collecting samples at and decades after diabetes onset are required to leverage the information they could provide.
Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan‐O randomized trial
Authors: Davies Melanie J. , Rosenstock Julio , Ali Amar , Russell‐Jones David , Souhami Elisabeth , Palmer Karen , Ji Chen , Niemoeller Elisabeth , Skolnik Neil 
Published: October 2021

AbstractAimsTo assess the efficacy and safety of iGlarLixi (the titratable fixed‐ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol).Materials and methodsThe LixiLan‐O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan‐O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening.ResultsThe mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2‐hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c −1.9% vs. −1.6% or −1.0% [−20 vs. −17 or −10 mmol/mol; 2‐hour PPG −7.2 vs. −4.6 or −5.5 mmol/L). Greater proportions of participants achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c <7% (<53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c <7% (<53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively.ConclusionsAdults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar.
The unequal burden of retirement reform: Evidence from Australia
Authors: Morris Todd 
Published: October 2021

AbstractAs governments try to contain rising expenditure on retirement pensions by increasing eligibility ages, there are concerns that such reforms disproportionately affect poorer households. Using detailed longitudinal data, I examine this trade‐off in the context of an Australian reform that increased women’s pension‐eligibility age from 60 to 65. While this reform significantly reduced government spending on women at affected ages, the negative effects on household incomes were concentrated among poorer households. These unequal impacts meant that the reform temporarily increased relative poverty rates among affected women by around four percentage points and inequality measures by 6% to 19%.