bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strength-Training Periodization: No Effect on Swimming Performance in Well-Trained Adolescent Swimmers
Authors: Schumann Moritz , Notbohm Hannah , Bäcker Simon , Klocke Jan , Fuhrmann Stefan , Clephas Christoph 
Published: March 2020

Purpose: To assess the effects of periodized versus nonperiodized dry-land strength training (DLST) on indices of swimming performance in well-trained adolescent swimmers. Methods: Sixteen athletes (10 boys and 6 girls; age 14.9 [1.1] y) performed similar endurance training for 16 weeks (29.1 [7.5] km·wk−1). During weeks 1 to 7, all athletes additionally performed 2 or 3 times weekly whole-body DLST (3 × 6–10 repetitions at 75–85% 1-repetition maximum [1RM]). Thereafter, the DLST frequency was maintained, but athletes were stratified into periodized (experimental, n = 9) and nonperiodized (control, n = 7) DLST groups. The experimental group performed maximal (3 × 3–4 repetitions at 85–90% 1RM) and explosive DLST (throws and unloaded jumps), while in the control group, DLST was maintained. Results: Swimming time at 4 mmol·L−1 of blood lactate improved after 7 weeks in both the experimental (+2.6% [1.8%], P = .033) and the control groups (+3.2% [2.4%], P = .081) and plateaued thereafter. Ten-meter start improved in both the experimental (−3.6% [2.5%], P = .039) and the control groups (−5.1% [2.2%], P = .054) throughout the entire intervention. Both groups improved in maximal weight lifted in half-squat (experimental, +19.6% [14.9%], P = .021; control, +25.7% [18.4%], P = .054) and bench press (experimental, +14.1% [4.8%], P = .018; control, +19.3% [11.1%], P = .051). Countermovement-jump height increased only in the experimental group throughout the intervention (+19.4% [7.0%], P = .024). The associations for the pooled changes in half-squat performance and 4 mmol·L−1 of blood lactate were statistically significant (r = .560, P = .024). Conclusions: The findings do not support the superior effects of DLST periodization in adolescent swimmers. However, the association between improvements in lower-body strength and swimming performance still indicates the importance of muscle strength in this age group.
Syn-kinematic ferroan high-K I-type granites from Dschang in southwestern Cameroon: U–Pb age, geochemistry and implications for crustal growth in the late Pan-African orogeny
Authors: Kwékam Maurice , Dunkl István , Fozing Eric Martial , Hartmann Gerald , Njanko Théophile , Tcheumenak Kouémo Jules , Njonfang Emmanuel 
Published: March 2020

Abstract

The Dschang granites, SW Cameroon, are post-Panafrican granitoids, hosted in Paleoproterozoic orthogneiss in the Western domain of the Central African fold belt. They include coarse-grained K-feldspar biotite granite and fine-grained magnetite granite. Magnetite forms nodules surrounded by a quartzo-feldsparthic halo. Major and trace element data of both granites show high SiO
2
, Al
2
O
3
, total alkalis and Ba and low TiO
2
, MgO, P
2
O
5
and Nb contents, conferring a fractionated I-type high-K alkali-calcic and weakly peraluminous character. Both granites are enriched in light rare earth elements and large ion lithophile elements, depleted in high field strength elements, and show a rare earth element pattern with Eu/Eu* = 0.3 to 0.9. Primitive mantle-normalized spidergrams display negative Nb, Ta and Ti anomalies, typical of their derivation from subduction-related post-collisional melt. Laser inductively coupled plasma mass spectrometry U–Pb data on zircons yielded crystallization ages of 578 +7/−11 Ma and 563+8/−3 Ma for the biotite and magnetite granites respectively. Inherited zircon (1991–1442 Ma), whole-rock Nd model ages in the range 2.1–1.9 Ga, highly negative
ε
Ndt
(−16 to −18) and initial
87
Sr/
86
Sr ratios in the range 0.7075–0.7114, support the remobilization of a Paleoproterozoic crust. The felsic magmas were probably produced by partial melting of Paleoproterozoic orthogneiss host rocks, under oxidizing conditions. Magnetite granite is also known from the Nkambé region. Such granites from both the Dschang and Nkambé regions suggest the presence of a Paleoproterozoic domain rich in iron mineralization. This domain potentially represents a Cu, Pb, Zn and Mo metallogenic province, heavily reworked during the Pan-African orogeny.
The Composite-File File System
Authors: Zhang Shuanglong , Roy Robert , Rumancik Leah , Wang An-I Andy 
Published: March 2020

The design and implementation of traditional file systems typically use the one-to-one mapping of logical files to their physical metadata representations. File system optimizations generally follow this rigid mapping and miss opportunities for an entire class of optimizations.
We designed, implemented, and evaluated a composite-file file system, which allows many-to-one mappings of files to metadata. Through exploring different mapping strategies, our empirical evaluation shows up to a 27% performance improvement under web server and software development workloads, for both disks and SSDs. This result demonstrates that our approach of relaxing file-to-metadata mapping is promising.
Risk SNP-Mediated Enhancer–Promoter Interaction Drives Colorectal Cancer through Both FADS2 and AP002754.2
Authors: Tian Jianbo , Lou Jiao , Cai Yimin , Rao Meilin , Lu Zequn , Zhu Ying , Zou Danyi , Peng Xiating , Wang Haoxue , Zhang Ming , Niu Siyuan , Li Yue , Zhong Rong , Chang Jiang , Miao Xiaoping 
Published: March 2020

Abstract

Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C&gt;G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17–1.36; P = 2.57 × 10–9). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer–promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a potential oncogene that facilitated colorectal cancer cell proliferation and xenograft growth in vitro and in vivo by increasing the metabolism of PGE2, an oncogenic molecule involved in colorectal cancer tumorigenesis. Our findings represent a novel mechanism by which a noncoding variant can facilitate long-range genome interactions to modulate the expression of multiple genes including not only mRNA, but also lncRNA, which provides new insights into the understanding of colorectal cancer etiology.

Significance:
This study provides an oncogenic regulatory circuit among several oncogenes including E2F1, FADS2, and AP002754.2 underlying the association of rs174575 with colorectal cancer risk, which is driven by long-range enhancer–promoter interaction loops.
Melanoma-Secreted Lysosomes Trigger Monocyte-Derived Dendritic Cell Apoptosis and Limit Cancer Immunotherapy
Authors: Santana-Magal Nadine , Farhat-Younis Leen , Gutwillig Amit , Gleiberman Annette , Rasoulouniriana Diana , Tal Lior , Netanely Dvir , Shamir Ron , Blau Rachel , Feinmesser Meora , Zlotnik Oran , Gutman Haim , Linde Ian L. , Reticker-Flynn Nathan E. , Rider Peleg , Carmi Yaron 
Published: March 2020

Abstract

The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage. Analysis of the immune systems of the organisms revealed that the numbers of tumor-infiltrating dendritic cells (TIDC) drastically decreased with time. Further, in contrast to the current paradigm, once melanoma was established, TIDC did not migrate into sentinel lymph nodes. Instead, they underwent local cell death due to excessive phagocytosis of lysosomes. Importantly, TIDC were required to license the cytotoxic activity of tumor CD8+ T cells, and in their absence, T cells did not lyse melanoma cells. Our results offer a paradigm shift regarding the role of TIDC and a framework to increase the efficacy of immunotherapies.

Significance:
This work redefines the role of monocyte-derived dendritic cells in melanoma and provides a novel strategy to increase the efficacy of T-cell–based immunotherapies in nonresponding individuals.
ATM Loss Confers Greater Sensitivity to ATR Inhibition Than PARP Inhibition in Prostate Cancer
Authors: Rafiei Shahrzad , Fitzpatrick Kenyon , Liu David , Cai Mu-Yan , Elmarakeby Haitham A. , Park Jihye , Ricker Cora , Kochupurakkal Bose S. , Choudhury Atish D. , Hahn William C. , Balk Steven P. , Hwang Justin H. , Van Allen Eliezer M. , Mouw Kent W. 
Published: March 2020

Abstract

Alterations in DNA damage response (DDR) genes are common in advanced prostate tumors and are associated with unique genomic and clinical features. ATM is a DDR kinase that has a central role in coordinating DNA repair and cell-cycle response following DNA damage, and ATM alterations are present in approximately 5% of advanced prostate tumors. Recently, inhibitors of PARP have demonstrated activity in advanced prostate tumors harboring DDR gene alterations, particularly in tumors with BRCA1/2 alterations. However, the role of alterations in DDR genes beyond BRCA1/2 in mediating PARP inhibitor sensitivity is poorly understood. To define the role of ATM loss in prostate tumor DDR function and sensitivity to DDR-directed agents, we created a series of ATM-deficient preclinical prostate cancer models and tested the impact of ATM loss on DNA repair function and therapeutic sensitivities. ATM loss altered DDR signaling, but did not directly impact homologous recombination function. Furthermore, ATM loss did not significantly impact sensitivity to PARP inhibition but robustly sensitized to inhibitors of the related DDR kinase ATR. These results have important implications for planned and ongoing prostate cancer clinical trials and suggest that patients with tumor ATM alterations may be more likely to benefit from ATR inhibitor than PARP inhibitor therapy.

Significance:
ATM loss occurs in a subset of prostate tumors. This study shows that deleting ATM in prostate cancer models does not significantly increase sensitivity to PARP inhibition but does sensitize to ATR inhibition.
See related commentary by Setton and Powell, p. 2085
Prediagnostic Circulating Levels of Sex Steroid Hormones and SHBG in Relation to Risk of Ductal Carcinoma In Situ of the Breast among UK Women
Authors: Arthur Rhonda S. , Xue Xiaonan , Rohan Thomas E. 
Published: March 2020

Abstract

Background:
Sex steroid hormones and sex hormone–binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma in situ (DCIS) of the breast, remain unclear.

Methods:
We used Cox proportional hazards regression models to estimate the associations of serum levels of estradiol (premenopausal women only), testosterone, and/or SHBG with DCIS risk among 182,935 women. After a median follow-up of 7.1 years, 186 and 531 DCIS cases were ascertained in premenopausal and postmenopausal women, respectively.

Results:
Total and free estradiol were positively associated with risk of DCIS among premenopausal women. The HRs for the highest versus the lowest tertiles were 1.54 (1.06–2.23) and 1.72 [95% confidence interval (CI), 1.15–2.57], respectively. Among postmenopausal women, elevated levels of free testosterone (FT), and to a lesser extent, total testosterone, were positively associated with DCIS risk. The HRs for the highest versus the lowest quartiles were 1.42 (95% CI, 1.09–1.85) and 1.16 (95% CI, 0.91–1.48), respectively. Serum SHBG levels were inversely associated with risk of DCIS among postmenopausal women (HRq4 vs. q1: 0.75; 95% CI, 0.56–0.99).

Conclusions:
This study suggests that elevated levels of estradiol are associated with increased risk of DCIS among premenopausal women, and that among postmenopausal women, elevated levels of testosterone, and particularly those of FT, are associated with increased DCIS risk, while elevated levels of SHBG are associated with reduced risk.

Impact:
These findings may be helpful in developing prevention strategies aimed at reducing breast cancer risk among premenopausal and postmenopausal women.
Periostin and Epithelial–Mesenchymal Transition Score as Novel Prognostic Markers for Leiomyosarcoma, Myxofibrosarcoma, and Undifferentiated Pleomorphic Sarcoma
Authors: Piano Maria Assunta , Brunello Antonella , Cappellesso Rocco , Del Bianco Paola , Mattiolo Adriana , Fritegotto Chiara , Montini Barbara , Zamuner Carolina , Del Fiore Paolo , Rastrelli Marco , Sommariva Antonio , De Salvo Gian Luca , Montesco Maria Cristina , Rossi Carlo Riccardo , Zagonel Vittorina , Calabrò Maria Luisa 
Published: March 2020

AbstractPurpose:Interpatient clinical variability in soft-tissue sarcomas (STS) highlights the need for novel prognostic markers supporting patient risk stratification. As sarcomas might exhibit a more mesenchymal or a more epithelial state, we focused on epithelial–mesenchymal and mesenchymal–epithelial transitions (EMT/MET) for prognostic clues, and selected three histotypes with variable aggressiveness.Experimental Design:The expression of EMT/MET-related factors was measured by qRT-PCR in 55 tumor samples from patients with leiomyosarcoma, myxofibrosarcoma, or undifferentiated pleomorphic sarcoma. The identified marker was further evaluated by IHC in 31 leiomyosarcomas and by measuring its circulating levels in 67 patients. The prognostic value of a sarcoma-tailored EMT score was analyzed. Epirubicin chemosensitivity and migration were studied in primary STS cultures. Associations with overall survival (OS) were assessed using Kaplan–Meier and Cox regression methods.Results:High expression of periostin, a mesenchymal matricellular protein, in sarcoma tissues (P = 0.0024), its high stromal accumulation in leiomyosarcomas (P = 0.0075), and increased circulation (&gt;20 ng/mL, P = 0.0008) were associated with reduced OS. High periostin expression [HR 2.9; 95% confidence interval (CI), 1.3–6.9; P = 0.0134] and circulation (HR 2.6; 95% CI, 1.3–5.1; P = 0.0086), and a mesenchymal EMT score (mesenchymal vs. transitioning; HR, 5.2; 95% CI, 2.1–13.0, P = 0.0005) were associated with increased risk in multivariable models. An intrinsic or induced mesenchymal state enhanced chemoresistance and migration in sarcoma cell lines.Conclusions:Although limited to a pilot study, these findings suggest that periostin might contribute prognostic information in the three studied STS histotypes. Moreover, a transitioning EMT score measured in the tumor might predict a less active and a more chemosensitive disease.
Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma
Authors: Atkins Michael B. , Rini Brian I. , Motzer Robert J. , Powles Thomas , McDermott David F. , Suarez Cristina , Bracarda Sergio , Stadler Walter M. , Donskov Frede , Gurney Howard , Oudard Stephane , Uemura Motohide , Lam Elaine T. , Grüllich Carsten , Quach Caroleen , Carroll Susheela , Ding Beiying , Zhu Qian (Cindy) , Piault-Louis Elisabeth , Schiff Christina , Escudier Bernard 
Published: March 2020

Abstract

Purpose:
Patient-reported outcomes (PRO) were evaluated in the phase III IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC).

Patients and Methods:
Patients were randomized 1:1 to receive atezolizumab 1,200 mg intravenous (i.v.) infusions every 3 weeks (q3w) plus bevacizumab 15 mg/kg i.v. q3w or sunitinib 50 mg per day orally 4 weeks on/2 weeks off. Patients completed the MD Anderson Symptom Inventory (MDASI), National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and Brief Fatigue Inventory (BFI) at baseline, q3w during treatment, at end of treatment, and during survival follow-up. Longitudinal and time to deterioration (TTD) analyses for core and RCC symptoms and their interference with daily life, treatment side-effect bother, and health-related quality of life (HRQOL) were evaluated.

Results:
The intent-to-treat population included 454 and 461 patients in the atezolizumab plus bevacizumab and sunitinib arms, respectively. Completion rates for each instrument were 83% to 86% at baseline and ≥ 70% through week 54. Milder symptoms, less symptom interference and treatment side-effect bother, and better HRQOL at most visits were reported with atezolizumab plus bevacizumab versus sunitinib. The TTD HR (95% CI) favored atezolizumab plus bevacizumab for core (HR, 0.50; 0.40–0.62) and RCC symptoms (HR, 0.45; 0.37–0.55), symptom interference (HR, 0.56; 0.46–0.68), and HRQOL (HR, 0.68; 0.58–0.81).

Conclusions:
PROs in IMmotion151 suggest lower overall treatment burden with atezolizumab plus bevacizumab compared with sunitinib in patients with treatment-naïve mRCC and provide further evidence for clinical benefit of this regimen.
Genomics, Morphoproteomics, and Treatment Patterns of Patients with Alveolar Soft Part Sarcoma and Response to Multiple Experimental Therapies
Authors: Groisberg Roman , Roszik Jason , Conley Anthony P. , Lazar Alexander J. , Portal Daniella E. , Hong David S. , Naing Aung , Herzog Cynthia E. , Somaiah Neeta , Zarzour Maria A. , Patel Shreyaskumar , Brown Robert E. , Subbiah Vivek 
Published: March 2020

Abstract
Overexpression of transcription factor 3 in alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multikinase inhibitors[tyrosine kinase inhibitor (TKI)] and immune checkpoint inhibitors (ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed to further elucidate novel targets. We retrospectively reviewed patients with ASPS treated on clinical trials. Demographic and clinical next-generation sequencing (NGS) profiles were collected. AACR GENIE database was queried to further evaluate aberrations in ASPS. Morphoproteomic analysis was carried out to better define the biology of ASPS with integration of genomic and proteomic findings. Eleven patients with ASPS were identified; 7 received NGS testing and mutations in CDKN2A (n = 1) and hepatocyte growth factor (n = 1) were present. Ten patients were treated with TKIs with stable disease as best response and 4 patients with ICI (three partial responses). Within GENIE, 20 patients were identified harboring 3 called pathogenic mutations. Tumor mutation burden was low in all samples. Morphoproteomic analysis confirmed the expression of phosphorylated c-Met. In addition, fatty acid synthase and phosphorylated-STAT3 were detected in tumor cell cytoplasm and nuclei. Patients with ASPS have a quiescent genome and derive clinical benefit from VEGF-targeting TKIs. Morphoproteomic analysis has provided both additional correlative pathways and angiogenic mechanisms that are targetable for patients with ASPS. Our study suggests that sequential therapy with TKIs and immune checkpoint inhibitors is a reasonable management strategy.
Deciphering the Immunomodulatory Capacity of Oncolytic Vaccinia Virus to Enhance the Immune Response to Breast Cancer
Authors: Umer Brittany A. , Noyce Ryan S. , Franczak Brian C. , Shenouda Mira M. , Kelly Rees G. , Favis Nicole A. , Desaulniers Megan , Baldwin Troy A. , Hitt Mary M. , Evans David H. 
Published: March 2020

Abstract

Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the intention of improving the therapeutic efficacy of VACV in breast cancer. We performed a head-to-head comparison of six mutant oncolytic VACVs, each harboring deletions in genes that modulate different cellular pathways, such as nucleotide metabolism, apoptosis, inflammation, and chemokine and interferon signaling. We found that even minor changes to the VACV genome can impact the immune cell compartment in the tumor microenvironment. Viral genome modifications had the capacity to alter lymphocytic and myeloid cell compositions in tumors and spleens, PD-1 expression, and the percentages of virus-targeted and tumor-targeted CD8+ T cells. We observed that while some gene deletions improved responses in the nonimmunogenic 4T1 tumor model, very little therapeutic improvement was seen in the immunogenic HER2/neu TuBo model with the various genome modifications. We observed that the most promising candidate genes for deletion were those that interfere with interferon signaling. Collectively, this research helped focus attention on the pathways that modulate the immune response in the context of VACV oncolytic virotherapy. They also suggest that the greatest benefits to be obtained with these treatments may not always be seen in “hot tumors.”
Latina/o/x Studies and Biblical Studies
Authors: Hidalgo Jacqueline M. 
Published: March 2020

Abstract
This essay introduces Latina/o/x studies for a biblical studies audience. It examines crucial themes that bridge Latina/o/x studies and biblical studies, themes such as identity and difference with special attention to ethnicity and race; also migration with attention to homing, diaspora, transnationalism, and citizenship. The place of Latina/o/x studies in relevant Hebrew Bible and New Testament scholarship on these topics is also discussed. Ultimately this essay argues that Latina/o/x studies’ epistemological commitments to complexity, relationality, particularity, and collaborative knowledge-making can help ground critical interpretive approaches in biblical studies. This essay also imagines a way that biblical studies—capaciously encompassing the study of Jewish and Christian literature in the ancient world as well as Jewish and Christian biblical reception and rejection histories, and the very category of scriptures more broadly—could deepen Latina/o/x studies own thinking about canon formation and history.