bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fish oil divergently enriches broiler meat with long chain ω-3 polyunsaturated fatty acids (LCω-3PUFAs) by modulating the ratio of ω-3 to ω-6 PUFAs without disrupting gut morphology and cardio-pulmonary morphometry
Authors: Hossain Md. Emran , Das Goutam Buddha , Bhowmik Priunka , Adhikary Kona , Sultan Md. Nahid , Islam Shilpi , Akter Nasima 
Published: October 2023

A trial was conducted for 35 days to investigate if replacement of soybean oil (SO) for fish oil (FO) influenced average daily feed intake (ADFI), average daily gain (ADG), final live weight (FLW), feed efficiency (FE), haemato-biochemical indices, carcass traits, cardio-pulmonary morphometry, gut morphology, nutrient digestibility, and fatty acid profile of the broiler chicken. A total of 350, day-old Ross-308 male broilers were distributed in a completely randomized design into five dietary treatment groups designated as FO0% (diet without FO, i.e., 100% SO), FO25% (diet containing 25% FO + 75% SO), FO50% (diet containing 50% FO + 50% SO), FO75% (diet containing 75% FO + 25% SO), and FO100% (diet containing 100% FO). Each treatment was replicated seven times containing 10 birds per replicate. Results indicated that complete replacement of SO for FO increased 4.7% FLW, 12.4% ADFI, 3.9% ADG, 16.2% HDL, and 8.6% CP. Although, FO contained 471.1% more ∑LCω-3PUFAs than SO, the FO-supplemented breast meat was enriched with net increment of 45.0% ∑LCω-3PUFAs and 81.0% ∑ω-3: ∑ω-6 at the expense of 7.1% FE and 26.8% MDA. Complete replacement of SO for FO did not compromise net profit. Hence, replacement of SO for FO may be commercially plausible.
A large deviation principle for reflected SPDEs on infinite spatial domain
Authors: Wang Ran , Zhang Beibei 
Published: October 2023

In this paper, we study a large deviation principle for a reflected stochastic partial differential equation on infinite spatial domain. A new sufficient condition for the weak convergence criterion proposed by Matoussi, Sabbagh and Zhang [A. Matoussi, W. Sabbagh and T.-S. Zhang, Large deviation principles of obstacle problems for quasilinear stochastic PDEs, Appl. Math. Optim. 83(2) (2021) 849–879] plays an important role in the proof.
Rethinking People Analytics With Inverse Transparency by Design
Authors: Zieglmeier Valentin , Pretschner Alexander 
Published: October 2023

Employees work in increasingly digital environments that enable advanced analytics. Yet, they lack oversight over the systems that process their data. That means that potential analysis errors or hidden biases are hard to uncover. Recent data protection legislation tries to tackle these issues, but it is inadequate. It does not prevent data misusage while at the same time stifling sensible use cases for data.
We think the conflict between data protection and increasingly data-driven systems should be solved differently. When access to an employees' data is given, all usages should be made transparent to them, according to the concept of inverse transparency. This allows individuals to benefit from sensible data usage while addressing the potentially harmful consequences of data misusage. To accomplish this, we propose a new design approach for workforce analytics software we refer to as inverse transparency by design.
To understand the developer and user perspectives on the proposal, we conduct two exploratory studies with students. First, we let small teams of developers implement analytics tools with inverse transparency by design to uncover how they judge the approach and how it materializes in their developed tools. We find that architectural changes are made without inhibiting core functionality. The developers consider our approach valuable and technically feasible. Second, we conduct a user study over three months to let participants experience the provided inverse transparency and reflect on their experience. The study models a software development workplace where most work processes are already digital. Participants perceive the transparency as beneficial and feel empowered by it. They unanimously agree that it would be an improvement for the workplace. We conclude that inverse transparency by design is a promising approach to realize accepted and responsible people analytics.
Retrospector: Rapid collaborative reflection to improve collaborative practices
Authors: Park Soya , Kulkarni Chinmay 
Published: October 2023

Online platforms for freelancing allow teams performing complex work to be assembled in a matter of minutes and dispersed nearly as quickly. With such short time frames, ad hoc and virtual teams have few opportunities to learn strategies and effective team practices to work with their colleagues. Without such practices, teams are prone to work sub-optimally and lack direction. One key challenge in virtual teams discovering effective team practices is that because the practices ought to involve situated knowledge, it takes time to coalesce, as team members learn about each other over time.
This work introduces Retrospector, that ad hoc teams can use to reflect collaboratively and reinforce effective team practices. Our interface accelerates the discovery of practices in situ and then guides them in reinforcing and applying these practices to future tasks. We conducted a between-subjects experiment (N=75) to assess our design with crowdworkers from the Amazon Mechanical Turk platform. This randomized controlled experiment showed that teams using our system for approximately six minutes of collaborative reflection were able to discover effective practices more successfully and had significantly improved team performance and viability. These results indicate that deliberate support for improving team practices can improve outcomes even through very short interaction. We conclude with design implications and opportunities for future work.
Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy 
Published: October 2023

Abstract

The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity induced by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. In vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, fibroblast-produced secreted factors stimulated treatment-independent enhancement of tumor cell proliferation. Spatial analyses indicated that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. These observations suggested an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate this hypothesis, a spatial agent–based model of stroma impact on proliferation/death dynamics was developed that was quantitatively parameterized using inferences from histologic analyses and experimental studies. The model demonstrated that the observed enhancement of tumor cell proliferation within stroma-proximal niches could enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, this study supports the existence of an indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.

Significance:
Integration of experimental research with mathematical modeling reveals an indirect microenvironmental chemoresistance mechanism by which stromal cells stimulate breast cancer cell proliferation and highlights the importance of consideration of proliferation/death dynamics.
See related commentary by Wall and Echeverria, p. 3667
Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase
Authors: Rawat Chitra , Ben-Salem Salma , Singh Nidhi , Chauhan Gaurav , Rabljenovic Anja , Vaghela Vishwa , Venkadakrishnan Varadha Balaji , Macdonald Jonathan D. , Dahiya Ujjwal R. , Ghanem Yara , Bachour Salam , Su Yixue , DePriest Adam D. , Lee Sanghee , Muldong Michelle , Kim Hyun-Tae , Kumari Sangeeta , Valenzuela Malyn May , Zhang Dingxiao , Hu Qiang , Cortes Gomez Eduardo , Dehm Scott M. , Zoubeidi Amina , Jamieson Christina A.M. , Nicolas Marlo , McKenney Jesse , Willard Belinda , Klein Eric A. , Magi-Galluzzi Cristina , Stauffer Shaun R. , Liu Song , Heemers Hannelore V. 
Published: October 2023

AbstractProstate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2–Skp2–p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression.Significance:The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression.See related commentary by Mishra et al., p. 4008
XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells
Authors: Marullo Rossella , Rutherford Sarah C. , Revuelta Maria V. , Zamponi Nahuel , Culjkovic-Kraljacic Biljana , Kotlov Nikita , Di Siervi Nicolás , Lara-Garcia Juan , Allan John N. , Ruan Jia , Furman Richard R. , Chen Zhengming , Shore Tsiporah B. , Phillips Adrienne A. , Mayer Sebastian , Hsu Jingmei , van Besien Koen , Leonard John P. , Borden Katherine L.B. , Inghirami Giorgio , Martin Peter , Cerchietti Leandro 
Published: October 2023

Abstract

Exportin-1 (XPO1), the main soluble nuclear export receptor in eukaryotic cells, is frequently overexpressed in diffuse large B-cell lymphoma (DLBCL). A selective XPO1 inhibitor, selinexor, received approval as single agent for relapsed or refractory (R/R) DLBCL. Elucidating the mechanisms by which XPO1 overexpression supports cancer cells could facilitate further clinical development of XPO1 inhibitors. We uncovered here that XPO1 overexpression increases tolerance to genotoxic stress, leading to a poor response to chemoimmunotherapy. Upon DNA damage induced by MYC expression or exogenous compounds, XPO1 bound and exported EIF4E and THOC4 carrying DNA damage repair mRNAs, thereby increasing synthesis of DNA damage repair proteins under conditions of increased turnover. Consequently, XPO1 inhibition decreased the capacity of lymphoma cells to repair DNA damage and ultimately resulted in increased cytotoxicity. In a phase I clinical trial conducted in R/R DLBCL, the combination of selinexor with second-line chemoimmunotherapy was tolerated with early indication of efficacy. Overall, this study reveals that XPO1 overexpression plays a critical role in the increased tolerance of cancer cells to DNA damage while providing new insights to optimize the clinical development of XPO1 inhibitors.

Significance:
XPO1 regulates the dynamic ribonucleoprotein nuclear export in response to genotoxic stress to support tolerance and can be targeted to enhance the sensitivity of cancer cells to endogenous and exogenous DNA damage.
See related commentary by Knittel and Reinhardt, p. 3
Educational Attainment and Cancer Incidence in a Large Nationwide Prospective Cohort
Authors: Hodge James M. , Patel Alpa V. , Islami Farhad , Jemal Ahmedin , Hiatt Robert A. 
Published: October 2023

Abstract

Background:
Educational attainment is a social determinant of health and frequently used as an indicator of socioeconomic status. Educational attainment is a predictor of cancer mortality, but associations with site-specific cancer incidence are variable. The aim of this study was to evaluate the association of educational attainment and site-specific cancer incidence adjusting for known risk factors in a large prospective cohort.

Methods:
Men and women enrolled in the American Cancer Society's Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline were included in this study (n = 148,965). Between 1992 and 2017, 22,810 men and 17,556 women were diagnosed with incident cancer. Cox proportional hazards regression models were used to estimate age- and multivariable-adjusted risk and 95% confidence intervals of total and site-specific cancer incidence in persons with lower versus higher educational attainment.

Results:
Educational attainment was inversely associated with age-adjusted cancer incidence among men but not women. For specific cancer sites, the multivariable-adjusted risk of cancer in the least versus most educated individuals remained significant for colon, rectum, and lung cancer among men and lung and breast cancer among women.

Conclusions:
Educational attainment is associated with overall and site-specific cancer risk though adjusting for cancer risk factors attenuates the association for most cancer sites.

Impact:
This study provides further evidence that educational attainment is an important social determinant of cancer but that its effects are driven by associated behavioral risk factors suggesting that targeting interventions toward those with lower educational attainment is an important policy consideration.
Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk
Authors: Larsson Susanna C. , Höijer Jonas , Sun Jing , Li Xue , Burgess Stephen , Michaëlsson Karl 
Published: October 2023

Abstract

Background:
Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk.

Methods:
Genetic variants associated with plasma ghrelin were identified in a GWAS comprising 10,742 Swedish adults in the discovery (N = 6,259) and replication (N = 4,483) cohorts. The association between ghrelin and gastrointestinal cancer was examined through a two-sample MR analysis using the identified genetic variants as instruments and GWAS data from the UK Biobank, FinnGen, and a colorectal cancer consortium.

Results:
GWAS found associations between multiple genetic variants within ±200 kb of the GHRL gene and plasma ghrelin. A two-sample MR analysis revealed that genetically predicted higher plasma ghrelin levels were associated with a lower risk of gastrointestinal cancer in UK Biobank and in a meta-analysis of the UK Biobank and FinnGen studies. The combined OR per approximate doubling of genetically predicted plasma ghrelin was 0.91 (95% confidence interval, 0.85–0.99; P = 0.02). Colocalization analysis revealed limited evidence of shared causal variants for plasma ghrelin and gastrointestinal cancer at the GHRL locus (posterior probability H4 = 24.5%); however, this analysis was likely underpowered.

Conclusions:
Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer.

Impact:
Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer.
Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya 
Published: October 2023

Abstract

Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we explored miRNA profiles in ASCL1-positive LUADs and identified several miRNAs closely associated with ASCL1 expression, including miR-375, miR-95–3p/miR-95–5p, miR-124–3p, and members of the miR-17∼92 family. Similar to small cell lung cancer, Yes1 associated transcriptional regulator (YAP1), a representative miR-375 target gene, was suppressed in ASCL1-positive LUADs. ASCL1 knockdown followed by miRNA profiling in a cell culture model further revealed that ASCL1 positively regulates miR-124–3p and members of the miR-17∼92 family. Integrative transcriptomic analyses identified ZFP36 ring finger protein like 1 (ZFP36L1) as a target gene of miR-124–3p, and IHC studies demonstrated that ASCL1-positive LUADs are associated with low ZFP36L1 protein levels. Cell culture studies showed that ectopic ZFP36L1 expression inhibits cell proliferation, survival, and cell-cycle progression. Moreover, ZFP36L1 negatively regulated several genes including E2F transcription factor 1 (E2F1) and snail family transcriptional repressor 1 (SNAI1). In conclusion, our study revealed that suppression of ZFP36L1 via ASCL1-regulated miR-124–3p could modulate gene expression, providing evidence that ASCL1-mediated regulation of miRNAs shapes molecular features of ASCL1-positive LUADs.

Implications:
Our study revealed unique miRNA profiles of ASCL1-positive LUADs and identified ASCL1-regulated miRNAs with functional relevance.
Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of
CDCP1
and Cardiac Fibrosis
Authors: Liu Duan , Wang Min , Murthy Vishakantha , McNamara Dennis M. , Nguyen Thanh Thanh L. , Philips Trudy J. , Vyas Hridyanshu , Gao Huanyao , Sahni Jyotan , Starling Randall C. , Cooper Leslie T. , Skime Michelle K. , Batzler Anthony , Jenkins Gregory D. , Barlera Simona , Pileggi Silvana , Mestroni Luisa , Merlo Marco , Sinagra Gianfranco , Pinet Florence , Krejčí Jan , Chaloupka Anna , Miller Jordan D. , de Groote Pascal , Tschumperlin Daniel J. , Weinshilboum Richard M. , Pereira Naveen L. 
Published: October 2023

BACKGROUND:
Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM.

METHODS:
A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction.

RESULTS:

The genome-wide association study identified a highly suggestive locus that mapped to the 5′-flanking region of the
CDCP1
(CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435;
P
=7.12×10
−7
). The variant allele was associated with improved cardiac function and decreased
CDCP1
transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis.

CONCLUSIONS:

CDCP1
may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.
Insomnia and Early Incident Atrial Fibrillation: A 16‐Year Cohort Study of Younger Men and Women Veterans
Authors: Gaffey Allison E. , Rosman Lindsey , Lampert Rachel , Yaggi Henry K. , Haskell Sally G. , Brandt Cynthia A. , Enriquez Alan D. , Mazzella Anthony J. , Skanderson Melissa , Burg Matthew M. 
Published: October 2023

Background
There is growing consideration of sleep disturbances and disorders in early cardiovascular risk, including atrial fibrillation (AF). Obstructive sleep apnea confers risk for AF but is highly comorbid with insomnia, another common sleep disorder. We sought to first determine the association of insomnia and early incident AF risk, and second, to determine if AF onset is earlier among those with insomnia.

Methods and Results
This retrospective analysis used electronic health records from a cohort study of US veterans who were discharged from military service since October 1, 2001 (ie, post‐9/11) and received Veterans Health Administration care, 2001 to 2017. Time‐varying, multivariate Cox proportional hazard models were used to examine the independent contribution of insomnia diagnosis to AF incidence while serially adjusting for demographics, lifestyle factors, clinical comorbidities including obstructive sleep apnea and psychiatric disorders, and health care utilization. Overall, 1 063 723 post‐9/11 veterans (Mean age=28.2 years, 14% women) were followed for 10 years on average. There were 4168 cases of AF (0.42/1000 person‐years). Insomnia was associated with a 32% greater adjusted risk of AF (95% CI, 1.21–1.43), and veterans with insomnia showed AF onset up to 2 years earlier. Insomnia‐AF associations were similar after accounting for health care utilization (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.17–1.39]), excluding veterans with obstructive sleep apnea (aHR, 1.38 [95% CI, 1.24–1.53]), and among those with a sleep study (aHR, 1.26 [95% CI, 1.07–1.50]).

Conclusions
In younger adults, insomnia was independently associated with incident AF. Additional studies should determine if this association differs by sex and if behavioral or pharmacological treatment for insomnia attenuates AF risk.