bluuebunny/crossref_metadata_2025_split huggingface dataset:
Channel mobility drives a diverse stratigraphic architecture in the dryland Mojave River (California, USA)
Authors: Ielpi Alessandro , Lapôtre Mathieu G.A. , Finotello Alvise , Ghinassi Massimiliano , D'Alpaos Andrea 
Published: February 2020

AbstractThe links between flood frequency and rates of channel migration are poorly defined in the ephemeral rivers typical of arid regions. Exploring these links in desert fluvial landscapes would augment our understanding of watershed biogeochemistry and river morphogenesis on early Earth (i.e. prior to the greening of landmasses). Accordingly, we analyse the Mojave River (California), one of the largest watercourses in the Great Basin of the western United States. We integrate discharge records with channel‐migration rates derived from dynamic time‐warping analysis and chronologically calibrated subsidence rates, thereby constraining the river's formative conditions. Our results reveal a slight downstream decrease in bankfull discharge on the Mojave River, rather than the downstream increase typically exhibited by perennial streams. Yet, the number of days per year during which the channel experiences bankfull or higher stages is roughly maintained along the river's length. Analysis of historical peak flood records suggests that the incidence of channel‐formative events responds to modulation in watershed runoff due to the precipitation in the river's headwaters over decades to centuries. Our integrated analysis finally suggests that, while maintaining hydraulic geometries that are fully comparable with many other rivers worldwide, ephemeral desert rivers akin to the Mojave are capable of generating a surprisingly wide range of depositional geometries in the stratigraphic record. © 2020 John Wiley & Sons, Ltd.
Summer‐born struggle: The effect of school starting age on health, education, and work
Authors: Balestra Simone , Eugster Beatrix , Liebert Helge 
Published: February 2020

AbstractChildren starting school older consistently exhibit better educational outcomes. In this paper, we underscore child development as a mechanism driving this effect. Using unique administrative data on health examinations, we study the causal effect of school starting age (SSA) on a child's probability of being diagnosed with special educational needs in early grades. Results show that children with higher SSA are less likely to develop behavioral problems and speech impediments, whereas learning disabilities, ADHD, and dyslexia/dyscalculia remain unaffected. Importantly, these effects only arise after primary school entry and are not due to preexisting health conditions. We also find that teachers tend to over‐refer relatively young children to special needs services, but this over‐referring behavior is not driving the results, which are based on psychologists' diagnoses. The SSA effect persists throughout compulsory schooling, resulting in higher test scores and better quality vocational training contracts. However, SSA does not affect employment, earnings, or disability insurance benefits at labor market entry.
Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Chari Ajai , Cornell Robert F. , Gasparetto Cristina , Karanes Chatchada , Matous Jeffrey V. , Niesvizky Ruben , Lunning Matthew , Usmani Saad Z. , Anderson Larry D. , Chhabra Saurabh , Girnius Saulius , Shustik Chaim , Stuart Robert , Lee Yihua , Salman Zeena , Liu Emily , Valent Jason 
Published: February 2020

AbstractPatients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first‐in‐class, once‐daily inhibitor of Bruton's tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra‐additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM. This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM). In this final analysis, we report results in patients who received the recommended phase 2 dose (RP2D; ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone), which was determined in phase 1. The primary efficacy endpoint was overall response rate (ORR). Fifty‐nine patients with RRMM received the RP2D (18 in phase 1 and 41 in phase 2b). These patients had received a median of three prior lines of therapy; 69% were refractory to bortezomib, and 90% were refractory to their last treatment. ORR in the RP2D population was 71% (stringent complete response and complete response: 3% each). Median duration of clinical benefit and median duration of response were both 6.5 months. Median progression‐free survival (PFS) was 7.4 months, and median overall survival (OS) was 35.9 months. High‐risk patients had comparable ORR and median PFS (67% and 7.7 months, respectively) to non–high‐risk patients, whose ORR was 73% and median PFS was 6.9 months, whereas median OS in high‐risk patients was 13.9 months and not reached in non–high‐risk patients. The most common grade ≥3 hematologic treatment‐emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non‐hematologic TEAE was hypertension (19%). In patients with RRMM treated with multiple previous lines of therapy, ibrutinib plus carfilzomib demonstrated anticancer activity within the expected efficacy range. No new safety signals were identified and the combination was well‐tolerated.
Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder
Authors: Mu Li , Lin Yezhe , Huang Xingbing , Ning Yuping , Wu Fengchun , Zhang Xiang Yang 
Published: February 2020

AbstractObjectiveSex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder.MethodsA total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions–Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high‐performance liquid chromatography.ResultsMen had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women.ConclusionsIn bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women.
Feeling the burn? A systematic review of burnout in pharmacists
Authors: McQuade Brianna M. , Reed Brent N. , DiDomenico Robert J. , Baker William L. , Shipper Andrea G. , Jarrett Jennie B. 
Published: February 2020

AbstractBurnout is high among health care professionals. In physicians, burnout is linked to suboptimal well‐being and patient care, but the overall landscape of pharmacist burnout is unknown. Synthesis of available data regarding pharmacist burnout is needed to better understand its effects on well‐being and professional practice. This systematic review sought to determine the prevalence and intensity of burnout in pharmacists. The aim of the study was the systematic review of articles on pharmacist burnout. PubMed, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO were searched for articles through February 13, 2019. Search strategies combined terms for pharmacists and burnout (including job satisfaction, stress, and resilience). The primary outcome was the proportion of pharmacists who met criteria for burnout. Secondary outcomes included the mean scores for Maslach Burnout Inventory (MBI) subscales, difference between pharmacist practice settings, and factors contributing to burnout. Raw scores and threshold proportions were pooled using a Hartung‐Knapp random‐effects model. Five articles reported the proportion of high emotional exhaustion (EE) and depersonalization (DP) and low personal accomplishment (PA), and nine articles reported individual MBI subscale scores, which were included for quantitative analysis. The proportion values of pharmacists with MBI subscale scores consistent with burnout were 41% (95% CI 27%‐54%), 20% (95% CI 7%‐32%), and 32% (95% 14%‐50%) for high EE, high DP, and low PA, respectively. Mean MBI subscales scores were 23.53 (95% CI 21.68‐25.39), 7.07 (95% CI 6.22‐7.92), and 36.51 (95% CI 34.34‐38.67) for EE, DP, and PA, respectively. Substantial heterogeneity was observed. The burnout prevalence among pharmacists is lower than previously reported, but notable. The average MBI subscale scores for high EE or DP or low PA in pharmacists did not meet criteria for burnout.
Gas6 negatively regulates the Staphylococcus aureus‐induced inflammatory response via TLR signaling in the mouse mammary gland
Authors: Zahoor Arshad , Yang Yaping , Yang Chao , Akhtar Muhammad , Guo Yingfang , Shaukat Aftab , Guo Meng‐yao , Deng Ganzhen 
Published: February 2020

AbstractStaphylococcus aureus (S. aureus)‐induced mastitis is the most frequent, pathogenic, and prevalent infection of the mammary gland. The ligand growth arrest‐specific 6 (Gas6) is a secretory protein that binds to and activates Tyro3, Axl, and MerTK receptors. This study explored the role of Gas6 in S. aureus‐induced mastitis. Our results revealed that TLR receptors initiate the innate immune response in mammary gland tissues and epithelial cells and that introducing S. aureus activates TLR2 and TLR6 to drive multiple intracellular mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) pathways. Moreover, S. aureus also induces Gas6, which then activates the TAM receptor kinase pathway, which is related to the inhibition of TLR2‐ and TLR6‐mediated inflammatory pathways through SOCS1 and SOCS3 induction. Gas6 absence alone was found to be involved in the downregulation of TAM receptor‐mediated anti‐inflammatory effects by inducing significantly prominent expression of TRAF6 and low protein and messenger RNA expression of SOCS1 and SOCS3. S. aureus‐induced MAPK and NF‐ĸB p65 phosphorylation were also dependent on Gas6, which negatively regulated the production of Pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) in S. aureus‐treated mammary tissues and mammary epithelial cells. Our in vivo and in vitro study uncovered the Gas6‐mediated negative feedback mechanism, which inhibits TLR2‐ and TLR6‐mediated MAPK and NF‐ĸB signaling by activating TAM receptor kinase (MerTK, Axl, and Tyro3) through the induction of SOCS1/SOCS3 proteins.
Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate
Authors: Shokouhian Mohammad , Bagheri Marziye , Poopak Behzad , Chegeni Rouzbeh , Davari Nader , Saki Najmaldin 
Published: February 2020

AbstractHematopoietic stem cells (HSCs) are quiescent cells with self‐renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self‐renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA. Also, TFs contribute to either facilitation or inhibition of gene expression through binding to enhancer or promoter regions of DNA. As a result, epigenetic factors and TFs regulate the activation or repression of HSCs genes, playing a central role in normal hematopoiesis. Given the importance of histone/DNA methylation and TFs in gene expression regulation, their aberrations, including changes in HSCs‐related methylation of histone/DNA and TFs (e.g., CCAAT‐enhancer‐binding protein α, phosphatase and tensin homolog deleted on the chromosome 10, Runt‐related transcription factor 1, signal transducers and activators of transcription, and RAS family proteins) could disrupt HSCs fate. Herewith, we summarize how dysregulations in the expression of genes related to self‐renewal, proliferation, and differentiation of HSCs caused by changes in epigenetic modifications and transcriptional networks lead to clonal expansion and leukemic transformation.
Body composition is prognostic and predictive of ipilimumab activity in metastatic melanoma
Authors: Chu Michael P. , Li Yuetong , Ghosh Sunita , Sass Shelley , Smylie Michael , Walker John , Sawyer Michael B. 
Published: February 2020

AbstractBackgroundBody composition is minimally investigated in an immunotherapy era. Specific body composition signals such as myosteatosis may reflect aspects of patients' immunology and thereby their ability to respond to immunotherapies. Ipilimumab is a key checkpoint inhibitor in metastatic melanoma. As an antibody, it may also be more accurately dosed using body composition parameters rather than weight alone. This retrospective study aimed to investigate body composition‐based dosing and outcomes.MethodsPretreatment computed tomography images from metastatic melanoma, ipilimumab‐treated patients from 2009 to 2014 were used to measure myosteatosis [skeletal muscle radiographic density or SMD, in Hounsfield units (HU)] and surface area (cm2) as previously described. Cut point analysis determined whether a level of ipilimumab dose and myosteatosis demonstrated differences in progression‐free (PFS) and overall survival (OS). Secondary endpoints included objective response rates and toxicities.ResultsOf 121 identified, 97 patients were evaluable. Baseline demographics included 56 years median age, 60% male participants, and 23.7% with BRAF mutations. SMD analysis identified cut‐offs of SMD < 42 in those with BMI < 25 kg/m2 and <20 HU in those with BMI ≥ 25 kg/m2, respectively. Low SMD patients had poorer median PFS [2.4 vs. 2.7 months, hazard ratio (HR) 1.76, P = 0.008] and OS (5.4 vs. 17.5 months, HR 2.47, P = 0.001), which remained significant in multivariate modelling. High SMD patients had more immune‐related adverse events, better objective response rates (17.9 vs. 3.3%, P = 0.051), and lower baseline neutrophil‐to‐lymphocyte ratio (21 vs. 39%, P = 0.049). Separately, patients receiving <2.03 mg/cm2 had improved median PFS (3.0 vs. 2.6 months, HR 1.88, P = 0.02) and OS (14.9 vs. 5.7 months, HR 1.98, P = 0.01).ConclusionsLow SMD and receiving >2.03 mg/cm2 are prognostic of poorer melanoma outcomes post ipilimumab. SMD may identify patients with flawed immunology and predict who may better respond to such therapy. Ipilimumab dosing by skeletal muscle index stands in contrast to weight‐based dosing and may demonstrate a more accurate method of antibody dosing.
The emerging roles of circular RNAs in CNS injuries
Authors: Qu Xiaolin , Li Zhenxing , Chen Jigang , Hou Lijun 
Published: February 2020

AbstractWith high morbidity and mortality worldwide, injuries to the central nervous system (CNS) usually result in devastating consequences. However, the underlying mechanisms have not been fully understood and current therapies are still limited. Circular RNA (circRNA) is a novel type of endogenous noncoding RNAs, characterized by covalently closed annular structure. It is gradually recognized that circRNAs are involved in multiple biological processes, such as acting as microRNA sponges or scaffolds during the assembly of protein complex and modulating the transcription of certain genes. Interestingly, circRNAs have been found to be highly expressed in the CNS, which indicates their neurospecificity. Several circRNAs have already been discovered to be associated with multiple pathophysiological processes following neurological diseases. Currently, the molecular roles of circRNAs in CNS injuries have gained increasing attention, leading to uninterrupted relevant researches. Herein, we presented a review of current studies on the role of circRNAs in CNS injuries. The therapeutic potency of circRNAs in CNS injuries was also analyzed.
Improving daily precipitation estimates for the Qinghai‐Tibetan plateau based on environmental similarity
Authors: Wang Yudan , Kong Yunfeng , Chen Hao , Zhao Lin 
Published: February 2020

AbstractDue to the scarcity of gauge observations and inaccuracy of satellite estimation, obtaining reliable daily precipitation estimates over the Qinghai‐Tibetan Plateau (QTP) remains challenging. In this article, an integrated scheme is developed based on the assumption that in a specific climatic region, the similarity of environmental conditions related to precipitation (SEP) in two locations is positively correlated to the similarities of occurrence and magnitude of precipitation between them. First, the QTP was divided into the northwestern arid, middle semi‐arid/semi‐humid, and southeastern humid climatic sub‐regions by grouping analysis. Second, based on modified weighted k‐nearest neighbour model, daily precipitation of target locations in these climatic sub‐regions were predicted by weighted regression of a group of gauge observations that have the largest SEP with the target locations. SEP was calculated by the following auxiliary environmental factors: longitude, latitude, elevation, Normalized Difference Vegetation Index, relative humidity, and CMORPH (Climate Prediction Center's morphing technique) daily precipitation estimates (original CMORPH). The validation results demonstrate the effectiveness of the proposed scheme. Compared with the original CMORPH and PDF‐calibrated CMORPH (CMORPH calibrated by probability density function matching plus optimal interpolation method) at daily, monthly, and yearly scales, the scheme improves the rain/no rain detection capacity and the accuracy of daily precipitation estimates. In addition, the daily precipitation estimates obtained from this scheme can present significant discrimination over specific geographic units, particularly the Qaidam Basin, the great bend of the Brahmaputra River, and Hengduan Mountain.
Safety and Outcomes of Early Enteral Nutrition in Circulatory Shock
Authors: Patel Jayshil J. , Rice Todd , Heyland Daren K. 
Published: February 2020

AbstractCirculatory shock is one of the most common reasons for an intensive care unit admission, has been shown to impair gut barrier and immune functions, and promotes dysbiosis. The exact timing and dose of enteral nutrition (EN) in circulatory shock remains unclear. In fact, because of fear of complications such as nonocclusive mesenteric ischemia and bowel necrosis and splanchnic steal phenomenon, clinicians may hesitate to start EN in critically ill patients with circulatory shock. In this narrative review, we identify and appraise contemporary evidence evaluating the safety and outcomes of EN in circulatory shock.
Analysis of volatile organic compounds in indoor environments using thermal desorption with comprehensive two‐dimensional gas chromatography and high‐resolution time‐of‐flight mass spectrometry
Authors: Veenaas Cathrin , Ripszam Matyas , Haglund Peter 
Published: February 2020

AbstractBuilding‐related health effects are frequently observed. Several factors have been listed as possible causes including temperature, humidity, light conditions, presence of particulate matter, and microorganisms or volatile organic compounds. To be able to link exposure to specific volatile organic compounds to building‐related health effects, powerful and comprehensive analytical methods are required. For this purpose, we developed an active air sampling method that utilizes dual‐bed tubes loaded with TENAX‐TA and Carboxen‐1000 adsorbents to sample two parallel air samples of 4 L each. For the comprehensive volatile organic compounds analysis, an automated thermal desorption comprehensive two‐dimensional gas chromatography high‐resolution time‐of‐flight mass spectrometry method was developed and used. It allowed targeted analysis of approximately 90 known volatile organic compounds with relative standard deviations below 25% for the vast majority of target volatile organic compounds. It also allowed semiquantification (no matching standards) of numerous nontarget air contaminants using the same data set. The nontarget analysis workflow included peak finding, background elimination, feature alignment, detection frequency filtering, and tentative identification. Application of the workflow to air samples from 68 indoor environments at a large hospital complex resulted in a comprehensive volatile organic compound characterization, including 178 single compounds and 13 hydrocarbon groups.
Effect of difluoroacetic acid and biological matrices on the development of a liquid chromatography–triple quadrupole mass spectrometry method for determination of intact growth factor proteins
Authors: Maráková Katarína , Rai Alex J. , Schug Kevin A. 
Published: February 2020

AbstractIn biological systems, variable protein expression is a crucial marker for numerous diseases, including cancer. The vast majority of liquid chromatography–triple quadrupole mass spectrometry‐based quantitative protein assays use bottom‐up methodologies, where proteins are subjected to proteolytic cleavage prior to analysis. Here, the effect of difluoroacetic acid and biological matrices on the developement of a multiple reaction monitoring based top‐down reversed‐phase liquid chromatography–triple quadrupole mass spectrometry method for analysis of cancer‐related intact proteins was evaluated. Seven growth factors (5.5–26.5 kDa; isoelectric points: 4.6–9.9) were analyzed on a wide‐pore C4 column. The optimized method was performed at 30°C, using a 0.2 mL/min flow rate, a 10 %B/min gradient slope, and 0.05% v/v difluoroacetic acid as a mobile phase modifier. The increase of mass spectrometry sensitivity due to the difluoroacetic acid (estimated limits of detection in biological matrices 1–500 ng/mL) significantly varied for proteins with lower and higher charge state distributions. Matrix effects, as well as the specificity of the method were assessed for variable biological samples and pretreatment methods. This work demonstrates method development to improve the ability to target intact proteins directly by more affordable triple quadrupole mass spectrometry instrumentation, which could be beneficial in many application fields.