bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the predictors of mutability among healthy human tissues inferred from mutations in single cell genome data
Authors: Oman Madeleine , Ness Rob W. 
Published: November 2023

AbstractStudying mutation in healthy somatic tissues is key for understanding the genesis of cancer and other genetic diseases. Mutation rate varies from site to site in the human genome by up to 100-fold and is influenced by numerous epigenetic and genetic factors including GC content, trinucleotide sequence context, and DNAse accessibility. These factors influence mutation at both local and regional scales and are often interrelated with one another, meaning that predicting mutability or uncovering its drivers requires modelling multiple factors and scales simultaneously. Historically, most investigations have focused either on analyzing the local sequence scale through triplet signatures or on examining the impact of epigenetic processes at larger scales, but not both concurrently. Additionally, sequencing technology limitations have restricted analyses of healthy mutations to coding regions (RNA-seq) or to those that have been influenced by selection (e.g. bulk samples from cancer tissue). Here we leverage single cell mutations and present a comprehensive analysis of epigenetic and genetic factors at multiple scales in the germline and three healthy somatic tissues. We create models that predict mutability with on average 2% error, and find up to 63-fold variation among sites within the same tissue. We observe varying degrees of similarity between tissues: the mutability of genomic positions was 93.4% similar between liver and germline tissues, but sites in germline and skin were only 85.9% similar. We observe both universal and tissue-specific mutagenic processes in healthy tissues, with implications for understanding the maintenance of germline versus soma and the mechanisms underlying early tumorigenesis.SummaryMutations in healthy tissues can reveal how genetic diseases originate. In this study, we explore how mutation rates vary across the human genome and what influences these variations. We leverage advanced single-cell analysis to analyze genetic and epigenetic factors in germline and three healthy tissues. We trained models that exhibit high accuracy and discover large variation within the same tissue. We also identified differences in mutability between tissues, suggesting both universal and tissue-specific mutation patterns with implications for understanding oncogenesis.
The Small Tumor Antigen of Merkel Cell Polyomavirus Accomplishes Cellular Transformation by Uniquely Localizing to the Nucleus Despite the Absence of a Known Nuclear Localization Signal
Authors: Thevenin Kaira R. , Tieche Isabella S. , Di Benedetto Cody E. , Schrager Matt , Dye Kristine N. 
Published: November 2023

ABSTRACTBackgroundMerkel Cell Carcinoma (MCC) is an aggressive skin cancer that is three times deadlier than melanoma. In 2008, it was found that 80% of MCC cases are caused by the genomic integration of a novel polyomavirus, Merkel Cell Polyomavirus (MCPyV), and the expression of its small and truncated large tumor antigens (ST and LT-t, respectively). MCPyV belongs to a family of human polyomaviruses; however, it is the only one with a clear association to cancer.MethodsTo investigate the role and mechanisms of various polyomavirus tumor antigens in cellular transformation, Rat-2, 293A, and human foreskin fibroblasts were transduced with pLENTI MCPyV LT-t, MCPyV ST, TSPyV ST, HPyV7 ST, or empty pLENTI and assessed through multiple transformation assays, and subcellular fractionations. One-way ANOVA tests were used to assess statistical significance.ResultsSoft agar, proliferation, doubling time, glucose uptake, and serum dependence assays confirmed ST to be the dominant transforming protein of MCPyV. Furthermore, it was found that MCPyV ST is uniquely transforming, as the ST antigens of other non-oncogenic human polyomaviruses such as Trichodysplasia Spinulosa Polyomavirus (TSPyV) and Human Polyomavirus 7 (HPyV7) were not transforming when similarly assessed. Identification of structural dissimilarities between transforming and non-transforming tumor antigens revealed that the uniquely transforming domain(s) of MCPyV ST are likely located within the structurally dissimilar loops of the MCPyV ST unique region. Of all known MCPyV ST cellular interactors, 62% are exclusively or transiently nuclear, suggesting that MCPyV ST localizes to the nucleus despite the absence of a canonical nuclear localization signal. Indeed, subcellular fractionations confirmed that MCPyV ST could achieve nuclear localization through a currently unknown, regulated mechanism independent of its small size, as HPyV7 and TSPyV ST proteins were incapable of nuclear translocation. Although nuclear localization was found to be important for several transforming properties of MCPyV ST, some properties were also performed by a cytoplasmic sequestered MCPyV ST, suggesting that MCPyV ST may perform different transforming functions in individual subcellular compartments.ConclusionsTogether, these data further elucidate the unique differences between MCPyV ST and other polyomavirus ST proteins necessary to understand MCPyV as the only known human oncogenic polyomavirus.
Spartin-mediated lipid transfer facilitates lipid droplet turnover
Authors: Wan Neng , Hong Zhouping , Parson Matthew A. H. , Korfhage Justin , Burke John E. , Melia Thomas J. , Reinisch Karin M. 
Published: November 2023

AbstractLipid droplets (LDs) are organelles critical for energy storage and membrane lipid homeostasis, whose number and size are carefully regulated in response to cellular conditions. The molecular mechanisms underlying lipid droplet biogenesis and degradation, however, are not well understood. The Troyer syndrome protein spartin (SPG20) supports LD delivery to autophagosomes for turnover via lipophagy. Here, we characterize spartin as a lipid transfer protein whose transfer ability is required for LD degradation. Spartin co-purifies with phospholipids and neutral lipids from cells and transfers phospholipids in vitro via its senescence domain. A senescence domain truncation that impairs lipid transfer in vitro also impairs LD turnover in cells while not affecting spartin association with either LDs or autophagosomes, supporting that spartin’s lipid transfer ability is physiologically relevant. Our data indicate a role for spartin-mediated lipid transfer in LD turnover.SignificanceThe Troyer syndrome protein spartin was proposed to function as a lipophagy receptor that delivers lipid droplets, organelles key for energy storage and membrane lipid homeostasis, to autophagosomes for degradation. We identify an additional function for spartin as a lipid transfer protein and show its transfer ability is required for lipid droplet degradation, including by lipophagy. Our data support that protein-mediated lipid transfer plays a role in lipid droplet turnover. Moreover, in spartin’s senescence domain we have discovered a new lipid transport module that likely also features in still undiscovered aspects of lipid droplet biology and membrane homeostasis.
Genomic transfers help to decipher the ancient evolution of filoviruses and interactions with vertebrate hosts
Authors: Taylor Derek J. , Barnhart Max H. 
Published: November 2023

AbstractAlthough several filoviruses are dangerous human pathogens, there is conflicting evidence regarding their origins and interactions with animal hosts. Here we attempt to improve this understanding using the paleoviral record over a geological time scale, protein structure predictions, tests for evolutionary maintenance, and phylogenetic methods that alleviate sources of bias and error. We found evidence for long branch attraction bias in the L gene tree for filoviruses, and that using codon-specific models and protein structural comparisons of paleoviruses ameliorated conflict and bias. We found evidence for four ancient filoviral groups, each with extant viruses and paleoviruses with open reading frames. Furthermore, we found evidence of repeated transfers of filovirus-like elements to mouse-like rodents. A filovirus-like nucleoprotein ortholog with an open reading frame was detected in three subfamilies of spalacid rodents (present since the Miocene). These elements were unique among the detected filovirus-like paleoviruses in possessing open reading frames, expression products, and evidence for purifying selection. Our finding of structural conservation over geological time for paleoviruses informs virus and paleovirus discovery methods. Our results resolve a deep conflict in the evolutionary framework for filoviruses and reveal that genomic transfers to vertebrate hosts with potentially functional co-options have been more widespread than previously appreciated.Author SummaryFiloviruses are a family of RNA viruses discovered in 1967 and notorious for spillover of the dangerous pathogens, Ebola virus and Marburg virus. However, their origins, deeper relations, diversity, and interactions with animal hosts remain controversial. Part of the confusion may be that differing rates of evolution among divergent viral lineages can create a bias termed long branch attraction (LBA). We tested for this scenario in the L protein gene sequence of filoviruses and found evidence that LBA is occurring leading to a false pairing of filovirus lineages associated with a fish and a snake. We found that using nucleotides instead of amino acids when inferring trees, paleoviral sequences with open reading frames, additional conserved genes, and comparisons of predicted protein structures can resolve the LBA. We found four major groups of filoviruses, with the paleoviral record and trees being consistent with a fish origin for the family. Moreover, we found evidence of a filovirus-like element in spalacid rodents that has been evolutionarily maintained at the open-reading frame, amino acid sequence and structural level for over 20 million years. This element was also expressed in the liver, a target of filoviral infections. We conclude that genomic interactions of filoviruses with vertebrates, including the co-option of viral genes, are more important than previously appreciated.
Attrition problems at food delivery app companies: is there a way out?
Authors: Subramanian R. Bala , Choudhary Archana 
Published: November 2023

Learning outcomes
After analysing this case study, students will be able to understand the relationship between compensation, reward management and gig workers’ behaviour; apply the theory of organizational behaviour related to compensation management to address the motivational issues; analyse the challenges in managing the gig workers’ expectations related to compensation; and design innovative ways of retaining gig workers, especially delivery partners among the gig workers.

Case overview/synopsis
In April 2022, Riya, who worked as a business development manager at a newly established food delivery app company named “Our Kitchen” (located in Hyderabad, India), attended a meeting where the chief executive officer expressed concern about the difficulty in retaining their delivery partners. The company provided food delivery services to the customers by procuring ordered food from partner restaurants in select Indian cities. The delivery partners of the company worked part-time and received a commission for the hours they worked. With the rising fuel cost, minimal career growth and negligible social security benefits, it was hard for them to continue in their jobs. As a result, there were high attrition rates in the food delivery company. This case study is about the attrition issue being faced by the company and explores various strategies through which Riya could think of retaining the delivery partners so that there was a win-win situation for both parties. The dilemma given in the case study would help in understanding the motivational theories and factors that encouraged delivery partners to work for these jobs.

Complexity academic level
The case study is ideally suited for discussing human resources concepts, especially problems related to the retention of delivery partners without reducing the profit of the organization. It will help in understanding the motivational factors leading to job satisfaction and how that will help in the retention of delivery partners. The case study can also be used to teach the executives in a management development programme. This will help them to understand the gig workers’ motivational factors and the causes of their attrition.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 6: Human resource management.
Working Out Loud: an intervention study to test an agile learning method
Authors: Augner Tabea , Schermuly Carsten C. , Jungmann Franziska 
Published: November 2023

Purpose
Today’s unpredictable and fast-changing work environment challenges researchers and organizations to rethink learning. In contrast to traditional learning designs, new learning frameworks such as agile learning are more learner centered, integrated into the workplace and socially shaped. The purpose of this study is to examine Working Out Loud (WOL) as an agile learning method.

Design/methodology/approach
This intervention study used a pre–post and six-month follow-up design (N = 507) to evaluate the effects of WOL on learners’ vigor (affective outcome), WOL behavior (behavioral outcome) and psychological empowerment (cognitive outcome) at work.

Findings
The authors compared the three longitudinal measurements using multilevel modeling. Results revealed that WOL could significantly increase learners’ WOL behavior and psychological empowerment at work in the post and six-month follow-up measurements. No effect was found on learners’ vigor at work.

Originality/value
This study highlights the need for research on new, more agile learning frameworks and discusses their relevance to the literature. Agile learning frameworks enable learners to be more autonomous and flexible, allowing them to better adapt to changing environmental demands.
Twin‐screw extrusion of vitamin D3/iron‐blend granules in corn and lentil composite flours: Stability, microstructure, and interaction of vitamin D3 with human osteoblast cells
Authors: Ahmed Jasim , Giri Bhupendra Raj , Reza Mohammed Arshad , Qasim Syed S. Bin , Thomas Linu , Al‐Attar Hasan , Maniruzzaman Mohammed 
Published: November 2023

AbstractVitamin D3 (VD3) and iron‐blend granules were blended with corn and lentil composite flour (75/25, w/w) and fed into a pilot‐scale twin‐screw extruder to produce ready‐to‐eat snacks. The morphology and microstructure of extruded snacks were examined using scanning electron microscopy with energy‐dispersive X‐ray (SEM–EDX), X‐ray powder diffraction, and FT‐IR. Differential scanning calorimetry and thermogravimetric analysis measured the melting temperature and thermal stability of the extrudates. SEM and FT‐IR analysis demonstrate that micronutrients are mixed well in formulations used in extrudates at high shear and high temperatures. The SEM–EDX exhibited the presence of iron, whereas high performance liquid chromatography measurements confirmed the significant retention of VD3 in the extruded snacks. The interaction between VD3 and human osteoblast cells was studied using live imaging and the MMT assay. Overall, for the first time, VD3 and Fe2+ blend granules have been used in an extrusion platform, which has significant potential for the intervention of VD3 and iron deficiencies.Practical ApplicationFor the first time, we reported the use of VD3/iron‐blend granules in extruded products. The findings of this work demonstrated the thermal stability and capability of providing adequate quantities of VD3 and iron in corn flour/lentil flour/VD3‐iron blend extruded snacks. Furthermore, the interaction of VD3 with osteoblast cells highlights the potential health benefits of the extrudates.
Oral compound probiotic supplements can improve the quality of life for patients with lung cancer during chemotherapy: A randomized placebo‐controlled study
Authors: Wei Hao , Yue Zhiying , Han Jialong , Chen Ping , Xie Ke , Sun Yu , Zhu Jiang 
Published: November 2023

AbstractBackgroundChemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy.MethodsThis randomized, double‐blind, placebo‐controlled trial enrolled chemotherapy‐naive patients with lung cancer who were scheduled to receive platinum‐based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP‐1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy.ResultsA total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP‐1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP‐1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001).ConclusionsCompound probiotic supplements can improve the quality of life and relieve chemotherapy‐related gastrointestinal side effects for lung cancer patients receiving platinum‐based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).
Comparing self‐esteem discrepancies in Pakistan and Canada
Authors: Vaughan‐Johnston Thomas I. , Imtiaz Faizan , Ji Li‐Jun , Hanif Rubina , Fowlie Devin I. , Jacobson Jill A. 
Published: November 2023

AbstractThe cross‐cultural universality of people's pursuit of positive self‐esteem is frequently disputed. Most research in this area has contrasted cultures of dignity (Western) and face cultures (East Asian), but less attention has been given to other cultures' views of self‐esteem. In the present work, we examined Pakistan as uniquely influenced by honour culture and South Asian argumentation culture principles, and we contrasted it with Canada (a Western culture of dignity). Across two studies, Pakistanis had less positive self‐esteem discrepancies (i.e., Pakistanis had minimal or no desire for higher self‐esteem) compared to Canadians (who desired much higher self‐esteem than they actually had). Pakistanis also believed less in the agentic benefits of high self‐esteem but more in the communal benefits of high self‐esteem than did Canadians. Differences in each cultures' beliefs about self‐esteem's causal powers partially accounted for the differences in self‐esteem discrepancies. These findings suggest unique conceptualizations of the value of self‐esteem in distinct cultures.
Early word learning is influenced by physical environments
Authors: Breitfeld Elise , Saffran Jenny R. 
Published: November 2023

AbstractDuring word learning moments, toddlers experience labels and objects in particular environments. Do toddlers learn words better when the physical environment creates contrasts between objects with different labels? Thirty‐six 21‐ to 24‐month‐olds (92% White, 22 female, data collected 8/21–4/22) learned novel words for novel objects presented using an apparatus that mimicked a shape‐sorter toy. The manipulation concerned whether or not the physical features of the environments in which objects occurred heightened the contrasts between the objects. Toddlers only learned labels for objects presented in environments where the apparatus heightened the contrast between the objects (b = .068). These results emphasize the importance of investigating word learning in physical environments that more closely approximate young children's everyday experiences with objects.
Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials
Authors: Silverii Giovanni Antonio , Monami Matteo , Gallo Marco , Ragni Alberto , Prattichizzo Francesco , Renzelli Valerio , Ceriello Antonio , Mannucci Edoardo 
Published: November 2023

AbstractAimTo conduct a meta‐analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment and thyroid cancer.Materials and MethodsIn this meta‐analysis of RCTs, we included studies comparing a GLP‐1RA with any comparator, lasting at least 52 weeks, and reporting the incidence of adverse events independently of the principal endpoint and population. All cases of thyroid cancer were collected.ResultsWe retrieved 64 trials, 26 of which reported at least one incident case of thyroid cancer. GLP‐1RA treatment was associated with a significant increase in the risk of overall thyroid cancer (Mantel‐Haenzel odds ratio [MH‐OR] 1.52 [95% confidence interval {CI} 1.01, 2.29]; P = 0.04, I2 = 0%), with a fragility index of 1, and a 5‐year number needed to harm of 1349. The association remained significant when including only trials lasting at least 104 weeks (MH‐OR 1.76 [95% CI 1.00, 3.12]; P = 0.05). No significant association was found for papillary thyroid cancer (MH‐OR 1.54 [95% CI 0.77, 3.06]; P = 0.22) or medullary thyroid cancer (MH‐OR 1.44 [95% CI 0.23, 9.16]; P = 0.55).ConclusionsOur meta‐analysis showed that GLP‐1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.
Reflections on corporate purpose and performance
Authors: Mayer Colin 
Published: November 2023

AbtstractWe are encountering growing crises that derive from a misconception of the nature of business. A revised understanding of profit should lie at the heart of the purpose of the corporation, namely, that it derives from producing solutions not problems for others. Firms should not profit from producing problems for others. There is a limit to the extent to which either competitive markets or regulation can ensure that. Instead, it must be intrinsic to the purpose of the business and, in the absence of this, both markets and regulation fail. Furthermore, public policy in the form of corporate taxation and public expenditure can be used to promote problem‐solving common purposes around shared prosperity. This has significant implications for business practice as well as policy.