bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of individuals with selected muscular dystrophies from the expanded pilot of the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) in the United States
Authors: Wallace Bailey , Smith K. Tiffany , Thomas Shiny , Conway Kristin M. , Westfield Christina , Andrews Jennifer G. , Weinert Richard O. , Do Thuy Quynh N. , Street Natalie ,   the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)
Published: July 2020

AbstractIntroductionData on muscular dystrophies (MDs), a heterogeneous group of heritable diseases hallmarked by progressive muscle deterioration, are scarce.ObjectiveWe describe cross‐sectional sociodemographic and clinical characteristics of individuals with congenital, distal, Emery‐Dreifuss, facioscapulohumeral, limb‐girdle, myotonic, or oculopharyngeal MD.MethodsThe study was conducted in four sites (Arizona, Colorado, Iowa, and 12 western New York counties) as a pilot expansion of the Muscular Dystrophy Surveillance, Tracking and Research Network, funded by the Centers for Disease Control and Prevention. MDs were detected in healthcare facilities and administrative data sources using International Classification of Disease codes. Our sample contains 1,723 individuals with a MD diagnosis and a healthcare encounter between January 1, 2007 and December 31, 2011.Results and ConclusionsIndividuals were mostly non‐Hispanic and white. Median ages ranged from 9.2 to 66.0 years. Most (98%) had health insurance. The proportion of individuals who were disabled or unable to work increased with age (range: 8.6–46.4%). People with limb‐girdle MD aged ≥18 years were more likely to be nonambulatory (range: 24.5–44.7%). The percentages of individuals with documented clinical interventions during the surveillance period were low. The most common cause of death was respiratory causes (46.3–57.1%); an ICD‐10 code for MD (G71.1 or G71.0) was reported for nearly one‐half. Our findings show wide variability in sociodemographic and clinical characteristics across MDs.
Molecular tools and applications of Euglena gracilis: From biorefineries to bioremediation
Authors: Khatiwada Bishal , Sunna Anwar , Nevalainen Helena 
Published: July 2020

AbstractEuglena gracilis is a promising source of commercially important metabolites such as vitamins, wax esters, paramylon, and amino acids. However, the molecular tools available to create improved Euglena strains are limited compared to other microorganisms that are currently exploited in the biotechnology industry. The complex poly‐endosymbiotic nature of the Euglena genome is a major bottleneck for obtaining a complete genome sequence and thus represents a notable shortcoming in gaining molecular information of this organism. Therefore, the studies and applications have been more focused on using the wild‐type strain or its variants and optimizing the nutrient composition and cultivation conditions to enhance the production of biomass and valuable metabolites. In addition to producing metabolites, the E. gracilis biorefinery concept also provides means for the production of biofuels and biogas as well as residual biomass for the remediation of industrial and municipal wastewater. Using Euglena for bioremediation of environments contaminated with heavy metals is of special interest due to the strong ability of the organism to accumulate and sequester these compounds. The published draft genome and transcriptome will serve as a basis for further molecular studies of Euglena and provide a guide for the engineering of metabolic pathways of relevance for the already established as well as novel applications.
Different strategies, distinguished cooperation efficiency, and brain synchronization for couples: An fNIRS‐based hyperscanning study
Authors: Tang Yun , Liu Xin , Wang Chenbo , Cao Miao , Deng Shining , Du Xiujuan , Dai Yuan , Geng Shujie , Fan Yun , Cui Lijuan , Li Fei 
Published: July 2020

AbstractIntroductionIndividuals may employ different strategies when cooperating with others. For example, when two participants are asked to press buttons simultaneously, they may press the buttons as quickly as possible (immediate response strategy) or press them in a delayed pattern (delayed response strategy). Despite recognition of interpersonal brain synchronization (IBS) as a fundamental neural mechanism of cooperation, it remains unclear how various strategies influence cooperative behavior and its neural activities.MethodsTo address this issue, 43 married couples were recruited to complete a button‐press cooperative task, during which IBS was recorded by functional near‐infrared spectroscopy hyperscanning.ResultsBehavioral results showed that couples who adopted a delayed response strategy performed better than those who adopted an immediate response strategy and those without any obvious strategy, and a new measure (cooperation coefficient) was used to index the level of cooperation. In addition, stronger IBS in the right frontal cortex was observed in the delayed response condition. The greater couples’ perceived parenting stress, the more likely they were to perform well in tasks and the stronger their brain synchronization, since they tended to choose the delayed response strategy.ConclusionThe delayed response strategy may better unify dyad partners’ response modes, trigger synchronized psychological processes, and enable their brains to become synchronized. The study extends understanding of cooperation by comparing the contributions of different strategies underlying cooperative behavior with corresponding neural evidence.
High throughput screening setup of a scale‐down device for membrane chromatography‐aggregate removal of monoclonal antibodies
Authors: Stein Dominik , Thom Volkmar , Hubbuch Jürgen 
Published: July 2020

AbstractIn biopharmaceutical process development, resin‐based high throughput screening (HTS) is well known for overcoming experimental limitations by permitting automated parallel processing at miniaturized scale, which results in fast data generation and reduced feed consumption. For membrane adsorber (MA), HTS solutions have so far only been available to a partial extent. Three case studies were performed with the aim of aligning HTS applications for MAs with those established for column chromatography: Process parameter range determination, mechanistic modeling (MM), and scalability. In order to exploit the MA typically features, such as high mass transfer and easy scalability, for scalable high throughput process development, a scale‐down device (SDD) for MA was developed. Its applicability is confirmed for a monoclonal antibody aggregate removal step. The first case study explores the experimental application of the SDD developed. It uses bind and elute mode and variations of pH and salt concentration to obtain process operation windows for ion‐exchange MAs Sartobind® S and Q. In the second case study, we successfully developed a mechanistic model based on parameters obtained from the SDD–HTS setup. The results proved to validate the use of the SDD developed for parameter estimation and thus model‐based process development. The third case study shows the transferability and scalability of data from the SDD–HTS setup using both a direct scale factor and MM. Both approaches show good applicability with a deviation below 20% in the prediction of 10% dynamic breakthrough capacity and reliable scale‐up from 0.42 to 800 ml.
Large granular lymphocyte leukemia serum and corresponding hematological parameters reveal unique cytokine and sphingolipid biomarkers and associations with STAT3 mutations
Authors: Olson Kristine C. , Moosic Katharine B. , Jones Marieke K. , Larkin Paige M. K. , Olson Thomas L. , Toro Mariella F. , Fox Todd E. , Feith David J. , Loughran Thomas P. 
Published: July 2020

AbstractLarge granular lymphocyte (LGL) leukemia is a rare hematological disorder with expansion of the T‐cell or natural killer (NK) cell lineage. Signal transducer and activator of transcription 3 (STAT3) exhibits somatic activating mutations in 30%‐40% of LGL leukemia cases. Transcriptional targets of STAT3 include inflammatory cytokines, thus previous studies have measured cytokine levels of LGL leukemia patients compared to normal donors. Sphingolipid metabolism is a growing area of cancer research, with efforts focused on drug discovery. To date, no studies have examined serum sphingolipids in LGL leukemia patients, and only one study compared a subset of cytokines between the T‐LGL and NK‐LGL subtypes. Therefore, here, we included both LGL leukemia subtypes with the goals of (a) measuring serum sphingolipids for the first time, (b) measuring cytokines to find distinctions between the subtypes, and (c) establishing relationships with STAT3 mutations and clinical data. The serum analyses identified cytokines (EGF, IP‐10, G‐CSF) and sphingolipids (SMC22, SMC24, SMC20, LysoSM) significantly different in the LGL leukemia group compared to normal donors. In a mixed STAT3 mutation group, D661Y samples exhibited the highest mean corpuscular volume (MCV) values. We explored this further by expanding the cohort to include larger groups of single STAT3 mutations. Male D661Y STAT3 samples had lower Hgb and higher MCV compared to wild type (WT) or Y640F counterparts. This is the first report examining large groups of individual STAT3 mutations. Overall, our results revealed novel serum biomarkers and evidence that D661Y mutation may show different clinical manifestation compared to WT or Y640F STAT3.
Long‐term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials
Authors: André Marc P. E. , Carde Patrice , Viviani Simonetta , Bellei Monica , Fortpied Catherine , Hutchings Martin , Gianni Alessandro M. , Brice Pauline , Casasnovas Olivier , Gobbi Paolo G. , Zinzani Pier Luigi , Dupuis Jehan , Iannitto Emilio , Rambaldi Alessandro , Brière Josette , Clément‐Filliatre Laurianne , Heczko Marian , Valagussa Pinuccia , Douxfils Jonathan , Depaus Julien , Federico Massimo , Mounier Nicolas 
Published: July 2020

AbstractPurposeWe explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials.Patients and methodsPrimary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT).ResultsAbout 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP.ConclusionsThis analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.
Disparities in cancer‐related healthcare among people with intellectual disabilities: A population‐based cohort study with health insurance claims data
Authors: Cuypers Maarten , Tobi Hilde , Huijsmans Cornelis A. A. , van Gerwen Lieke , ten Hove Michiel , van Weel Chris , Kiemeney Lambertus A. L. M. , Naaldenberg Jenneken , Leusink Geraline L. 
Published: July 2020

AbstractBackgroundConcerns have been raised about the accessibility and quality of cancer‐related care for people with intellectual disabilities (ID). However, there is limited insight into cancer incidence and the utilization of cancer care at the ID population level to inform targeted cancer control strategies. Therefore, we aimed to examine differences in the utilization of cancer‐related care between people with and without ID, identified through diagnostic codes on health insurance claims.MethodsIn a population‐based cohort study, Dutch individuals of all ages who received residential care through the Chronic Care Act due to an ID (n = 65 183) and an age and sex‐matched sample of persons without ID (1:2 ratio), who were cancer‐free at enrollment in 2013 were followed through 2015. Incidence rates (IRs) of newly started cancer care and IR ratios (IRRs) with 95% CIs were used to compare groups. Separate analyses were performed per cancer type.ResultsIndividuals with ID received less cancer‐related care than individuals without (IRR = 0.64, 95% CI 0.62‐0.66). Differences increased with age and were larger for females than for males. Utilization of care for cancers within the national screening program (female breast, cervical, and colon cancer) was lower for people with ID compared to people without ID.ConclusionCancer may be underdiagnosed and/or undertreated in people with ID, or cancer is truly less prevalent in this population. In particular, the differences detected between males and females with ID, and the potential underutilization of national screening programs, require urgent follow‐up investigations.
Five‐Step Enantioselective Synthesis of Islatravir via Asymmetric Ketone Alkynylation and an Ozonolysis Cascade
Authors: Patel Niki R. , Huffman Mark A. , Wang Xiao , Ding Bangwei , McLaughlin Mark , Newman Justin A. , Andreani Teresa , Maloney Kevin M. , Johnson Heather C. , Whittaker Aaron M. 
Published: July 2020

AbstractA 5‐step enantioselective synthesis of the potent anti‐HIV nucleoside islatravir is reported. The highly efficient route was enabled by a novel enantioselective alkynylation of an α,β‐unsaturated ketone, a unique ozonolysis‐dealkylation cascade in water, and an enzymatic aldol‐glycosylation cascade.
Pd‐Catalyzed Transfer of Difluorocarbene for Three Component Cross‐Coupling†
Authors: Xu Zhi‐Wei , Zhang Wei , Lin Jin‐Hong , Jin Chuan‐Ming , Xiao Ji‐Chang 
Published: July 2020

Summary of main observation and conclusionOutstanding accomplishments have been achieved in the chemistry of difluorocarbene, but transition‐ metal‐catalyzed transfer of difluorocarbene for coupling remains a challenging task. Herein, we describe a Pd‐catalyzed coupling of difluorocarbene with two aryl carbon centers to give difluoromethylenation products, which cannot be obtained by any previous difluorocarbene‐transformation method.
The effect of chemotherapy on survival in patients with nonmetastatic male breast cancer: A population‐based observational study
Authors: Pan Hong , Zhang Kai , Wang Ming , Ling Lijun , Wang Shui , Zhou Wenbin 
Published: July 2020

BackgroundMale breast cancer is a rare malignant disease, accounting for <1% of all breast cancers. The treatment of male breast cancer is mainly extrapolated from the enormous literature and clinical experience in women. The objective of the current study was to assess the relationship between adjuvant chemotherapy and survival in a large population‐based cohort of patients with early‐stage male breast cancer.MethodsMen with invasive stage I to stage III breast cancer were identified in the Surveillance, Epidemiology, and End Results cancer database from 1990 to 2014. The effect of chemotherapy on survival was determined using multivariable Cox regression.ResultsOf 2713 male patients enrolled, 1817 (66.9%) did not receive chemotherapy. Age, T classification, N classification, tumor grade, and progesterone receptor (PR) status were found to be strong predictors of chemotherapy administration. Chemotherapy was associated with a significant 26% reduction in all‐cause mortality (P < .001) and a marginally significant 21% reduction in breast cancer–specific mortality (P = .085). For men with PR‐negative breast cancer, use of chemotherapy was associated with improved breast cancer–specific survival (hazards ratio [HR], 0.50; 95% confidence interval [95% CI], 0.28‐0.91 [P = .023]) and overall survival (HR, 0.54; 95% CI, 0.37‐0.77 [P = .001]). However, chemotherapy did not improve the breast cancer–specific survival for all men with PR‐positive tumors (P = .959); it was associated with improved overall survival (HR, 0.78; 95% CI, 0.66‐0.92 [P = .004]) for men with PR‐positive stage II and stage III breast cancer.ConclusionsChemotherapy should be considered for men with PR‐negative, nonmetastatic breast cancer and PR‐positive, stage II and stage III breast cancer.
Use of high‐resolution full‐field optical coherence tomography and dynamic cell imaging for rapid intraoperative diagnosis during breast cancer surgery
Authors: Yang Houpu , Zhang Shuwei , Liu Peng , Cheng Lin , Tong Fuzhong , Liu Hongjun , Wang Siyuan , Liu Miao , Wang Chaobin , Peng Yuan , Xie Fei , Zhou Bo , Cao Yingming , Guo Jiajia , Zhang Yuanyuan , Ma Yingteng , Shen Danhua , Xi Peng , Wang Shu 
Published: July 2020

BackgroundAlthough traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full‐field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery.MethodsFFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin‐eosin) for purposes of comparison.ResultsA total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor‐positive, 48; tumor‐negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%).ConclusionsThese timely and tissue‐sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.
Nomogram predicting survival as a selection criterion for postmastectomy radiotherapy in patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes
Authors: Tang Yu , Zhang Yu-Jing , Zhang Na , Shi Mei , Wen Ge , Cheng Jing , Wang Hong-Mei , Liu Min , Wang Xiao-Hu , Guo Qi-Shuai , Wu Hong-Fen , Ma Chang-Ying , Jin Jing , Liu Yue-Ping , Song Yong-Wen , Fang Hui , Ren Hua , Wang Shu-Lian , Li Ye-Xiong 
Published: July 2020

BackgroundThe role of postmastectomy radiotherapy (PMRT) in women with pT1‐T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT.MethodsThe authors retrospectively evaluated 4869 patients with pT1‐T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease‐free survival and OS rates were calculated using the Kaplan‐Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model.ResultsAfter a median follow‐up of 65.9 months, the 5‐year OS, disease‐free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate‐risk (P < .001) and high‐risk groups (P = .004), but not in the low‐risk group (P = .728).ConclusionsThe authors developed a nomogram that is predictive of OS among women with pT1‐T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT.
Identification of regenerative processes in neonatal spinal cord injury in the opossum (Monodelphis domestica): A transcriptomic study
Authors: Wheaton Benjamin J. , Sena Johnny , Sundararajan Anitha , Umale Pooja , Schilkey Faye , Miller Robert D. 
Published: July 2020

AbstractThis study investigates the response to spinal cord injury in the gray short‐tailed opossum (Monodelphis domestica). In opossums spinal injury early in development results in spontaneous axon growth through the injury, but this regenerative potential diminishes with maturity until it is lost entirely. The mechanisms underlying this regeneration remain unknown. RNA sequencing was used to identify differential gene expression in regenerating (SCI at postnatal Day 7, P7SCI) and nonregenerating (SCI at Day 28, P28SCI) cords +1d, +3d, and +7d after complete spinal transection, compared to age‐matched controls. Genes showing significant differential expression (log2FC ≥ 1, Padj ≤ 0.05) were used for downstream analysis. Across all time‐points 233 genes altered expression after P7SCI, and 472 genes altered expression after P28SCI. One hundred and forty‐seven genes altered expression in both injury ages (63% of P7SCI data set). The majority of changes were gene upregulations. Gene ontology overrepresentation analysis in P7SCI gene‐sets showed significant overrepresentations only in immune‐associated categories, while P28SCI gene‐sets showed overrepresentations in these same immune categories, along with other categories such as “cell proliferation,” “cell adhesion,” and “apoptosis.” Cell‐type–association analysis suggested that, regardless of injury age, injury‐associated gene transcripts were most strongly associated with microglia and endothelial cells, with strikingly fewer astrocyte, oligodendrocyte and neuron‐related genes, the notable exception being a cluster of mostly downregulated oligodendrocyte‐associated genes in the P7SCI + 7d gene‐set. Our findings demonstrate a more complex transcriptomic response in nonregenerating cords, suggesting a strong influence of non‐neuronal cells in the outcome after injury and providing the largest survey yet of the transcriptomic changes occurring after SCI in this model.