bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotopic exchange of oxygen, sulfur, hydrogen and copper between aqueous phase and the copper minerals brochantite, libethenite and olivenite
Authors: Majzlan Juraj , Mathur Ryan , Milovský Rastislav , Milovská Stanislava 
Published: October 2021

AbstractFractionation factors for the isotopes of O, H, S, or Cu (as appropriate) were determined for the minerals brochantite [Cu4(SO4)(OH)6], libethenite [Cu2(PO4)(OH)] and olivenite [Cu2(AsO4)(OH)] and corresponding aqueous solutions at temperatures between 30 and 70°C. All samples used for this determination were synthetic and the degree of fractionation was expressed as 1000 ln α = (A × 106/T2) + B, where A and B are empirical parameters. A few natural libethenite samples from its type locality Ľubietová-Podlipa were also analysed and compared to the prediction based on the isotopic composition of meteoric water and our fractionation factors. The hydrogen fractionation factors agreed with the prediction well, whereas those for oxygen did not. A possible explanation is the disequilibrium of aqueous phosphate (and also arsenate) species and the solution in our experiments or the interaction of meteoric fluids with the isotopically heavy (in terms of oxygen) country rocks. Because the effects of isotopic disequilibrium in our experiments cannot be ruled out, the oxygen fractionation factors should be used with caution. The determined fractionation factors can be used as an isotope geothermometer, given that it can be proven that the phases of interest precipitated from the same fluid in equilibrium. Libethenite is predicted to have slightly lower δ65Cu values than its parental solution, but brochantite slightly higher δ65Cu values than its parental solution. Simple forward models, simulating neutralisation or reduction of mine drainage, show that precipitation of these minerals and removal of the co-existing fluid, could cause isotopic variations (in δ65Cu) on the order of 1‰ or more.
Pevonedistat targets malignant cells in myeloproliferative neoplasms in vitro and in vivo via NFκB pathway inhibition
Authors: Kong Tim , Laranjeira Angelo B.A. , Collins Taylor B. , De Togni Elisa S. , Wong Abigail J. , Fulbright Mary C. , Ruzinova Marianna , Celik Hamza , Challen Grant A. , Fisher Daniel A.C. , Oh Stephen T. 
Published: October 2021

Abstract
Targeted inhibitors of JAK2 (eg ruxolitinib) often provide symptomatic relief for myeloproliferative neoplasm (MPN) patients, but the malignant clone persists and remains susceptible to disease transformation. These observations suggest that targeting alternative dysregulated signaling pathways may provide therapeutic benefit. Previous studies identified NFκB pathway hyperactivation in myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) that was insensitive to JAK2 inhibition. Here, we provide evidence that NFκB pathway inhibition via pevonedistat targets malignant cells in MPN patient samples as well as in MPN and patient-derived xenograft mouse models that are nonredundant with ruxolitinib. Colony forming assays revealed preferential inhibition of MF colony growth compared with normal colony formation. In mass cytometry studies, pevonedistat blunted canonical TNFα responses in MF and sAML patient CD34+ cells. Pevonedistat also inhibited hyperproduction of inflammatory cytokines more effectively than ruxolitinib. Upon pevonedistat treatment alone or in combination with ruxolitinib, MPN mouse models exhibited reduced disease burden and improved survival. These studies demonstrating efficacy of pevonedistat in MPN cells in vitro as well as in vivo provide a rationale for therapeutic inhibition of NFκB signaling for MF treatment. Based on these findings, a Phase 1 clinical trial combining pevonedistat with ruxolitinib has been initiated.
Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma
Authors: Zinzani Pier Luigi , Ramchandren Radhakrishnan , Santoro Armando , Paszkiewicz-Kozik Ewa , Gasiorowski Robin , Johnson Nathalie A. , de Oliveira Jose S. R. , Buccheri Valeria , Perini Guilherme Fleury , Dickinson Michael , McDonald Andrew , Özcan Muhit , Sekiguchi Naohiro , Zhu Ying , Raut Monika , Saretsky Todd L. , Nahar Akash , Kuruvilla John 
Published: October 2021

Abstract
KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD; ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (&gt;90%) and through week 24 (&gt;80%) was demonstrated across treatment groups (PRO analysis set: pembrolizumab, n = 146; BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31]; P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74]; P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT.
Regulatory association of long noncoding RNAs and chromatin accessibility facilitates erythroid differentiation
Authors: Ren Yunxiao , Zhu Junwei , Han Yuanyuan , Li Pin , Wu Jing , Qu Hongzhu , Zhang Zhaojun , Fang Xiangdong 
Published: October 2021

Abstract
Erythroid differentiation is a dynamic process regulated by multiple factors, whereas the interaction between long noncoding RNAs (lncRNAs) and chromatin accessibility and its influence on erythroid differentiation remains unclear. To elucidate this interaction, we used hematopoietic stem cells, multipotent progenitor cells, common myeloid progenitor cells, megakaryocyte-erythroid progenitor cells, and erythroblasts from human cord blood as an erythroid differentiation model to explore the coordinated regulatory functions of lncRNAs and chromatin accessibility by integrating RNA-seq and ATAC-seq data. We revealed that the integrated network of chromatin accessibility and lncRNAs exhibits stage-specific changes throughout the erythroid differentiation process and that the changes at the erythroblast stage of maturation are dramatic. We identified a subset of stage-specific lncRNAs and transcription factors (TFs) that associate with chromatin accessibility during erythroid differentiation, in which lncRNAs are key regulators of terminal erythroid differentiation via an lncRNA-TF-gene network. LncRNA PCED1B-AS1 was revealed to regulate terminal erythroid differentiation by coordinating GATA1 dynamically binding to the chromatin and interacting with the cytoskeleton network during erythroid differentiation. DANCR, another lncRNA that is highly expressed at the megakaryocyte-erythroid progenitor cell stage, was verified to promote erythroid differentiation by compromising megakaryocyte differentiation and coordinating with chromatin accessibility and TFs, such as RUNX1. Overall, our results identify the associated network of lncRNAs and chromatin accessibility in erythropoiesis and provide novel insights into erythroid differentiation and abundant resources for further study.
Genetic features and clinical outcomes of patients with isolated and comutatedDDX41-mutated myeloid neoplasms
Authors: Alkhateeb Hassan B. , Nanaa Ahmad , Viswanatha David , Foran James M. , Badar Talha , Sproat Lisa , He Rong , Nguyen Phuong , Jevremovic Dragan , Salama Mohamad E. , Greipp Patricia , Gangat Naseema , Tefferi Ayalew , Litzow Mark R. , Mangaonkar Abhishek A. , Shah Mithun Vinod , Patnaik Mrinal , Al-Kali Aref 
Published: October 2021

AbstractDDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.
Uncontrolled asthma from childhood to young adulthood associates with airflow obstruction
Authors: Mogensen Ida , Hallberg Jenny , Ekström Sandra , Bergström Anna , Melén Erik , Kull Inger 
Published: October 2021

IntroductionLung function development from childhood to young adulthood is important for lung health later in life. We investigated the association between asthma control and lung function from 8 to 24 years of age.MethodsA total of 668 participants from the population-based BAMSE cohort study, with persistent or incidental asthma and between 8 and 24 years of age, were included. Asthma was defined as controlled or uncontrolled at each examination based on the Global Initiative for Asthma (GINA) criteria. Dynamic spirometry was performed at 8, 16 and 24 years of age. Associations between uncontrolled asthma and pre-bronchodilation forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were evaluated with a generalised estimating equation model, as overall associations and at each examination. Unadjusted and adjusted (for sex, current asthma, allergic sensitisation, body mass index, smoking, smoke exposure, inhaled corticosteroid use) analyses were done; and were thereafter stratified by sex, elevated blood eosinophils (≥0.3×109 cells·µL−1), elevatedFENO(≥25 ppb), allergic sensitisation and ever/never smoking.ResultsUncontrolled asthma was associated with a lower overall FEV1/FVC z-score from 8 to 24 years of age (adjusted regression coefficient −0.11; 95% CI (−0.20 to −0.02; p=0.016). After stratification, this association was primarily seen among females (adjusted regression coefficient −0.170; 95% CI (−0.298 to −0.044; p=0.009) and participants with elevatedFENO(regression coefficient −0.207; 95% CI −0.342 to −0.073; p=0.002), in contrast to males and participants with normalFENO.ConclusionUncontrolled asthma is associated with airflow obstruction from childhood to young adulthood. This highlights the importance of active management of asthma during growth.
CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study
Authors: Lorè Nicola I. , De Lorenzo Rebecca , Rancoita Paola M. V. , Cugnata Federica , Agresti Alessandra , Benedetti Francesco , Bianchi Marco E. , Bonini Chiara , Capobianco Annalisa , Conte Caterina , Corti Angelo , Furlan Roberto , Mantegani Paola , Maugeri Norma , Sciorati Clara , Saliu Fabio , Silvestri Laura , Tresoldi Cristina ,   Bio Angels for COVID-BioB Study Group, Farina Nicola , De Filippo Luigi , Battista Marco , Grosso Domenico , Gorgoni Francesca , Di Biase Carlo , Moretti Alessio Grazioli , Granata Lucio , Bonaldi Filippo , Bettinelli Giulia , Delmastro Elena , Salvato Damiano , Magni Giulia , Avino Monica , Betti Paolo , Bucci Romina , Dumoa Iulia , Bossolasco Simona , Morselli Federica , Ciceri Fabio , Rovere-Querini Patrizia , Di Serio Clelia , Cirillo Daniela M. , Manfredi Angelo A. 
Published: October 2021

Abstract
Background
Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment.

Methods
We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers.

Results
Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233–0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547–0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital.

Conclusions
CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Graphic abstract
Effect of anogenital distance on stress urinary incontinence
Authors: Ekmez Murat , Ekmez Fırat 
Published: October 2021

Abstract
Background
To clarify the effect of anogenital distance (AGD) on stress urinary incontinence (SUI) in female patients.

Methods
Charts of patients who admitted to urogynecology polyclinic between December 2020 and February 2021 were analyzed retrospectively. The AGD parameters including anogenital distance from the anus to the clitoris (AGDAC), anogenital distance from the anus to the fourchette (AGDAF) and genital hiatus (GH) were measured. To identify effect of ADG parameters on SUI, patients were divided into the two subgroups (patients with SUI and without SUI). Demographic characteristics of patients and perineal anatomy measurement were compared between groups.

Results
Totally, 256 female patients met study inclusion criteria. In comparison of patients with and without SUI, demonstrated that age, weight, height, and BMI were similar between groups (p = 0.200, p = 0.455, p = 0.131, and p = 0.215, respectively). The AGDAF was measured 22.6 mm in patients with SUI and 25.5 mm in patients without SUI (p = 0.014). In contrast, AGDAC was significantly longer in patients with SUI (81.1 mm vs. 72.2 mm, p = 0.001). Also, GH was significantly longer in patients with SUI (p = 0.016). Multivariate logistic regression analysis revealed that one mm increment in AGDAC and GH, is associated with 1.108- and 1.038-fold time of SUI development risk, respectively (p = 0.001 and p = 0.004). In contrast, decrease in AGDAF is resulted with significantly higher risk for SUI (p = 0.001).

Conclusion
The present study demonstrated that shorter AGDAF, and longer AGDAC and GH were resulted with significantly higher incidence of SUI. Considering the ease and non-invasiveness of anogenital distance measurement, an important implication of the results of current study is that it is a measurement that can be easily performed during routine gynecological and obstetric examinations as a suitable tool for use in the prediction of women who will develop stress incontinence in the future.
Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: a diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle aspiration
Authors: Maruta Akinori , Iwashita Takuji , Yoshida Kensaku , Uemura Shinya , Yasuda Ichiro , Shimizu Masahito 
Published: October 2021

Abstract
Background
A pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified.

Aims
To evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer.

Methods
Between January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis.

Results
The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) (p < 0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) (p = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not.

Conclusions
EUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.
Patient-centeredness in the multimorbid elderly: a focus group study
Authors: Kanat Manuela , Schaefer Jonas , Kivelitz Laura , Dirmaier Jörg , Voigt-Radloff Sebastian , Heimbach Bernhard , Glattacker Manuela 
Published: October 2021

Abstract
Background
Patient-centeredness (PC) aims to adapt health care to the individual needs and preferences of patients. An existing integrative model of PC comprises several dimensions of PC which have not yet been investigated from the patients’ perspective. Older patients with multimorbidity represent a target group for patient-centered care, as their care needs are particularly complex and should be addressed individually. We aimed to assess the perspective that older patients with multimorbidity have of patient-centered care and to examine the transferability of the integrative model of PC to this specific population.

Method
We performed 4 guided focus group interviews with a total of 20 older individuals with multimorbidity. The focus group interviews were audio-recorded and transcribed verbatim. Patients’ statements were content-analyzed applying an a priori designed system of categories that included the dimensions of PC from the integrative model and the additional category ‘prognosis and life expectancy’, which had emerged from an initial literature search on aspects of PC specific to the multimorbid elderly.

Results
The new category ‘prognosis and life expectancy’ was confirmed and expanded to ‘individual care needs related to aging and chronic disesase’. All dimensions of our integrative PC model were confirmed for older patients with multimorbidity. Among these, we found that eight dimensions (individual care needs related to aging and chronic disease, biopsychosocial perspective, clinician-patient communication, essential characteristics of the clinician, clinician-patient-relationship, involvement of family and friends, coordination and continuity of care, access to care) were complemented by aspects specific to this target population.

Conclusions
The integrative PC model is applicable to the population of older patients with multimorbidity. For a population-specific adaptation, it might be complemented by the dimension ‘individual care needs in aging and chronic disease’, in conjunction with age-specific aspects within existing dimensions. Together with corresponding results from a Delphi survey, our adapted PC model will serve as the basis for a subsequent systematic review of instruments measuring PC in older patients with multimorbidity.

Trial registration
PROSPERO (https://www.crd.york.ac.uk/prospero; CRD42018084057; 2018/02/01), German Clinical Trials Register (www.drks.de; DRKS00013309; 2018/01/23).
Perceived discrimination and health outcomes among middle-aged and older adults in India: results of a national survey in 2017–2018
Authors: Pengpid Supa , Peltzer Karl 
Published: October 2021

Abstract
Background
The study aimed to estimate the associations between perceived discrimination and poor physical health, poor mental health, and health risk behaviours in middle-aged and older adults in a national population survey in India.

Methods
The sample included 72,262 middle-aged and older adults from a cross-sectional national community dwelling survey in India in 2017–2018.

Results
The prevalence of moderate (1–2 types) perceived discrimination was 10.7%, and high (3–6 types) perceived discrimination was 6.6%. In the final adjusted logistic, linear or Poisson regression analyses, moderate and/or high perceived discrimination was significantly positively associated with poor mental health (low life satisfaction, poor cognitive functioning, insomnia symptoms, and depressive symptoms), poor physical health (pain conditions count, and functional limitations), and health risk behaviours (heavy episodic drinking and physical inactivity).

Conclusion
Perceived discrimination is associated with poor mental health, poor physical health, and health risk behaviour, emphasising the need to consider perceived discrimination in various physical and mental health contexts.