bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyploid cancer cells reveal signatures of chemotherapy resistance
Authors: Schmidt Michael J. , Naghdloo Amin , Prabakar Rishvanth K. , Kamal Mohamed , Cadaneanu Radu , Garraway Isla P. , Lewis Michael , Aparicio Ana , Zurita-Saavedra Amado , Corn Paul , Kuhn Peter , Pienta Kenneth J. , Amend Sarah R. , Hicks James 
Published: August 2024

AbstractTherapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression- free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and their expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.
Factors associated with pharmacologic serum concentration of Magnesium and corresponding obstetric outcomes among women with severe pre-eclampsia at Iringa Regional Referral Hospital
Authors: Kileo Joshua Stephen , matovelo Shubi , Kitinusa Gabriel 
Published: August 2024

AbstractIntroductionSevere pre-eclampsia is managed by using Magnesium sulphate to prevent its progress into eclampsia with a success rate of more than 50%. This study aimed at establishing reliable data pertaining factors influencing pharmacologic serum concentration of Magnesium and their correlation to obstetric outcomes.MethodsThis study was carried out at Iringa regional referral hospital, spanning six months from November 2023 to April 2024. A convenient sampling technique was used to recruit 121 pre-eclamptic patients. Recruited women were tested serum Magnesium at admission, 4 and 12 hours post initial administration of MgSO4. IBM SPSS version 29 was used for analysis where, Continuous variables were analyzed by using median and interquartile range while categorical variables were analyzed using frequency and percentages. The associations between variables were determined using chi-square tests, univariate, and multivariate binary regression models. A p value<0.05 was considered statistically significant.ResultsThe median age of participants were (29±10 IQR), the median serum Mg at admission was (0.8±0.29 IQR) Mmol/L majority with low 53(43.8%) levels. Proportion of subtherapeutic serum Mg was 38.8% with median of (1.9±1.02 IQR) Mmol/L. Multivariate regression showed that; low serum Mg at admission [p<0.001, OR= 9.17, 95% CI (3.07-27.37)], Creatinine level [p = 0.012, OR= 4.49, 95% CI (1.38-14.6)], Overweight [p= 0.002, OR= 5.52, 95% CI (1.83-16.68)] and proteinuria +++[p-value = 0.004, OR= 7.13, 95% CI (1.84-26.86)] were significantly associated with subtherapeutic level. After adjusting with other factors, it was found that subtherapeutic level [p<0.001, OR=25.44(5.73-112.90)], elevated creatinine [p=0.040, OR=3.59(1.66-12.15)], Reduced urine output [p=0.001, OR=6.69(2.15-20.90)] were significant predictors of adverse maternal outcomes.ConclusionSubtherapeutic serum Magnesium which significantly predict adverse obstetric outcomes, is influenced by factors which can be monitored and be useful in effective management of severe pre-eclampsia. This can help in administering tailored dose of MgSO4for better outcomes.
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection
Authors: Negi Shloka , Stenton Sarah L. , Berger Seth I. , McNulty Brandy , Violich Ivo , Gardner Joshua , Hillaker Todd , O’Rourke Sara M , O’Leary Melanie C. , Carbonell Elizabeth , Austin-Tse Christina , Lemire Gabrielle , Serrano Jillian , Mangilog Brian , VanNoy Grace , Kolmogorov Mikhail , Vilain Eric , O’Donnell-Luria Anne , Délot Emmanuèle , Miga Karen H. , Monlong Jean , Paten Benedict 
Published: August 2024

AbstractMore than 50% of families with suspected rare monogenic diseases remain unsolved after whole genome analysis by short read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing, and providing haplotype-resolved methylation profiling. To evaluate LRS’s additional diagnostic yield, we sequenced a rare disease cohort of 98 samples, including 41 probands and some family members, using nanopore sequencing, achieving per sample ∼36x average coverage and 32 kilobase (kb) read N50 from a single flow cell. Our Napu pipeline generated assemblies, phased variants, and methylation calls. LRS covered, on average, coding exons in ∼280 genes and ∼5 known Mendelian disease genes that were not covered by SRS. In comparison to SRS, LRS detected additional rare, functionally annotated variants, including SVs and tandem repeats, and completely phased 87% of protein-coding genes. LRS detected additionalde novovariants, and could be used to distinguish postzygotic mosaic variants from prezygoticde novos. Eleven probands were solved, with diverse underlying genetic causes includingde novoand compound heterozygous variants, large-scale SVs, and epigenetic modifications. Our study demonstrates LRS’s potential to enhance diagnostic yield for rare monogenic diseases, implying utility in future clinical genomics workflows.
Staphylococcus aureusTetracycline Resistance and Co-resistance in a Doxy-PEP-Eligible Population
Authors: Mittelstaedt Rachel , Kanjilal Sanjat , Helekal David , Robbins Gregory K. , Grad Yonatan H. 
Published: August 2024

AbstractInStaphylococcus aureusinfections in men eligible for doxycycline post-exposure prophylaxis (doxy-PEP), tetracycline non-susceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select forS. aureusmulti-drug resistance, underscoring the importance of surveillance.
Genomic Epidemiology and Microevolution of the Zoonotic PathogenCorynebacterium ulcerans
Authors: Crestani Chiara , Passet Virginie , Rethoret-Pasty Martin , Criscuolo Alexis , Zidane Nora , Brémont Sylvie , Badell Edgar , Brisse Sylvain 
Published: August 2024

AbstractCorynebacterium ulceransis an emerging zoonotic pathogen that belongs to theCorynebacterium diphtheriae(Cd) species complex (CdSC), and that causes diphtheria-like infections in humans. Our understanding of the transmission, phylogeography and evolution ofC. ulceransremains limited, in part due to the lack of a standardized genomic epidemiology toolkit.The aim of this work was to develop a core genome multi-locus sequence typing (cgMLST) scheme for high-resolution genotyping and classification ofC. ulceransstrains, and to explore transmission, spatial spread and genomic evolution among 582C. ulceransisolates from sporadic clinical cases and reported case clusters.The cgMLST scheme combines 1,628 loci with highly reproducible allele calls and shows high strain subtyping resolution. We demonstrate its utility for capturing population structure by defining sublineages (SL, maximum 940 allele differences) and clonal groups (CG, 194 allele differences, AD) and for epidemiological surveillance by defining genetic clusters, i.e., previously undetected chains of transmission (25 AD). Genetic clusters correspond to cryptic and case clusters that were associated with specific geographical regions within France. MajorC. ulceranssublineages (SL325, SL331, SL339) and clonal groups (CG325, CG331, CG583) showed strong associations with diphtheria toxin variants and tox-carrying prophages or other genetic elements. The evolutionary dynamics oftoxgene presence or absence varied sharply among clonal groups. The cgMLST scheme is publicly available (https://bigsdb.pasteur.fr/diphtheria) and provides a common framework for investigating the ecology, evolution and variations in virulence amongC. ulceransstrains. The implementation of a standardized high-resolution genotyping method will also facilitate the tracing ofC. ulceranstransmission and spread across hosts and from local to global spatial scales.
Multi-Layer Autocatalytic Feedback Enables Integral Control Amidst Resource Competition and Across Scales
Authors: Zand Armin M. , Anastassov Stanislav , Frei Timothy , Khammash Mustafa 
Published: August 2024

AbstractIntegral feedback control strategies have proven effective in regulating protein expression in unpredictable cellular environments. These strategies, grounded in model-based designs and control theory, have advanced synthetic biology applications. Autocatalytic integral feed-back controllers, utilizing positive autoregulation for integral action, are particularly promising due to their similarity to natural behaviors like self-replication and positive feedback seen across biological scales. However, their effectiveness is often hindered by resource competition and context-dependent couplings. This study addresses these challenges with a multi-layer feedback strategy, enabling population-level integral feedback and multicellular integrators. We provide a generalized mathematical framework for modeling resource competition in complex genetic networks, supporting the design of intracellular control circuits. Our controller motif demonstrated precise regulation in tasks ranging from gene expression control to population growth in multi-strain communities. We also explore a variant capable of ratiometric control, proving its effectiveness in managing gene ratios and co-culture compositions in engineered microbial ecosystems. These findings offer a versatile approach to achieving robust adaptation and homeostasis from subcellular to multicellular scales.
Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes
Authors: Mallimadugula Upasana L. , Cruz Matthew A. , Vithani Neha , Zimmerman Maxwell I. , Bowman Gregory R. 
Published: August 2024

AbstractCryptic pockets are of growing interest as potential drug targets, particularly to control protein-nucleic acid interactions that often occur via flat surfaces. However, it remains unclear whether cryptic pockets contribute to protein function or if they are merely happenstantial features that can easily be evolved away to achieve drug resistance. Here, we explore whether a cryptic pocket in the Interferon Inhibitory Domain (IID) of viral protein 35 (VP35) of Zaire ebolavirus aids its ability to bind double-stranded RNA (dsRNA). We use simulations and experiments to study the relationship between cryptic pocket opening and dsRNA binding of the IIDs of two other filoviruses, Reston and Marburg. These homologs have nearly identical structures but block different interferon pathways due to different affinities for blunt ends and backbone of the dsRNA. Simulations and thiol-labeling experiments demonstrate that the homologs have varying probabilities of pocket opening. Subsequent dsRNA-binding assays suggest that closed conformations preferentially bind dsRNA blunt ends while open conformations prefer binding the backbone. Point mutations that modulate pocket opening proteins further confirm this preference. These results demonstrate the open cryptic pocket has a function, suggesting cryptic pockets are under selective pressure and may be difficult to evolve away to achieve drug resistance.
Odoribacter splanchnicusmitigatesSalmonella-induced gut inflammation and its associated pathogenesis via its secreted bacteriocin
Authors: Hajra Dipasree , Mukherjee Debapriya , Vij Rhea , Rajmani Raju S , Dadireddy Venkatareddy , Das Deepakash , Husain Tanweer , Ganji Mahipal , Tatu Utpal , Chakravortty D 
Published: August 2024

ABSTRACTFoodborne pathogens continue to be a leading concern of health hazards worldwide claiming the lives of millions. The emergence of drug-resistant strains poses a great threat to global world health management. Therefore, designing novel therapeutic strategies aiming to overcome pathogen burden is of utmost importance. Here, we identified the crucial role of a gut-commensal species,Odoribacter splanchnicusin mitigatingSalmonellapathogenesis in mice by inhibiting gut vascular barrier disruption, acute inflammatory infection signs,in vivobiofilm formation and by preserving tight junction protein functions upon pre-colonization. Further, ourin vitrostudies revealed that not only liveO. splanchnicus(OS) but also its culture supernatant inhibitSalmonellabiofilm formation, intracellular proliferation in human intestinal cells, and its virulence gene expression. In addition, OS’s inhibitory effect onSalmonellais specific asEnterococcus faecalisfails to exert an inhibitory effect onSalmonella. Further, our results depicted that the specific protective role of OS acts over a broad spectrum as it confers protection against flagellated Gram-positive,Listeria monocytogenesand Gram-negative,SalmonellaTyphimurium foodborne pathogens, as opposed to non-flagellatedShigella flexneri. Moreover, OS conferred protection even after its administration to mice post-establishment of infection highlighting its therapeutic potential. Using several biochemical and proteomics approaches, we characterized the key active molecule secreted by OS to limit intracellularSalmonellaandListeriareplication in human intestinal epithelial cells by regulating key virulence effectors and flagella. Collectively, our study highlights the broad-spectrum protective role of OS in mitigatingSalmonellaandListeriapathogenesis and implicates its therapeutic potential.
The nexus of stewardship and sustainability in supply chains: revealing the impact of purchasing social responsibility on innovativeness and operation performance
Authors: Zouari Dorsaf , Viale Laurence , Ruel Salomée , Stek Klaas 
Published: August 2024

Purpose
The authors mobilise stewardship theory, which delves into trust and collaboration dynamics, advocating for long-term gains through actions beneficial to the broader community. Used as a fundamental framework to conceptualise the model, stewardship theory enhances the understanding of the effect of purchasing social responsibility (PSR) practices to foster innovativeness and performance through the supply chain (SC). This study aims to examine the relationship between PSR, SC innovativeness (SC-INNO) and SC operational performance (SCOP). In addition, the moderating effect of sustainability labels on these relationships will be studied.

Design/methodology/approach
Based on survey data from 177 organisations analysed through partial least square structural equation modelling, the results suggest that PSR has a positive and significant effect on SC-INNO and SCOP. In addition, SC-INNO plays a partial mediation role since the direct effect between PSR and SCOP is validated. Furthermore, the moderating effects of holding a sustainability label and industry type about PSR and SCOP are supported.

Findings
The results indicate a significant positive influence of PSR on both SC-INNO and operational performance. SC-INNO is found to partially mediate the PSR–SCOP relationship. Moreover, sustainability labels and industry type significantly moderate the effects of PSR on SCOP.

Originality/value
The findings extend stewardship theory into the sustainable purchasing and supply management field by providing empirical support for PSR as a reflection of stewardship behaviours by fostering innovation and performance throughout the SC.
Evaluating the critical resultant impacts of the COVID-19 pandemic on quality assurance of cross-border construction logistics and supply chain
Authors: Ghansah Frank Ato , Lu Weisheng 
Published: August 2024

PurposeThis study aims to identify and examine the critical resultant impacts of the coronavirus (COVID-19) pandemic on quality assurance (QA) of cross-border construction logistics and supply chain (CB-CLSC).Design/methodology/approachThis is achieved via embedded mixed-method design pragmatically involving desk literature review, survey and interviews from related experts within the Hong Kong Special Administrative Region (SAR)–Mainland China links. The design is further integrated with descriptive analysis, criticality test, rank agreement analysis, spearman correlation test and sentiment analysis.FindingsThe study revealed 10 critical resultant impacts of the COVID-19 pandemic on the QA of CB-CLSC, with the top three including “increased use of digital technologies (M10)”, “worker absence, labour shortage and decrease in work rate (M3)” and “changes to how construction sites operate (M9)”. Three underlying dimensions were discovered among all the critical resultant impacts: “cost-time-worker (CTW)-related impacts”, “work contract and operation (WCO)-related impacts” and “work process (WP)-related impacts”. The critical resultant impacts are reflected in the time, cost, raw materials and work processes, and this could manifest as negative as well as an opportunity to position the QA system to be adequate during the pandemic and post-pandemic era.Originality/valueThe study contributes to the knowledge body as it identifies and examines the critical resultant impacts of the COVID-19 pandemic on the QA of CB-CLSC. This is original research with invaluable primary data collected in the form of surveys and interviews from construction quality experts within the Hong Kong (SAR)–Mainland China links, known as the world’s factory.
Strategies for improving project risk management via communication and integration: the case of Jordan
Authors: Hatamleh Muhammad T. , Alzarrad Ammar , Alghossoon Abdullah , Alhusban Mohammad , Ogunrinde Olugbenro 
Published: August 2024

PurposeProject information is widely and thoroughly exchanged within construction projects. However, the risk management process exhibits deficiencies in coordination and visibility, particularly in developing countries. Practitioners in developing countries often engage in Project Risk Management (PRiM) using practices that inadvertently hinder project success, frequently resulting in suboptimal outcomes. Therefore, this research explores practices within Project Integration Management (PIM) and Project Communication Management (PCmM) that could enhance PRiM and improve managerial proficiency to achieve project success in developing countries.Design/methodology/approachThe PIM, PCmM and PRiM processes were explored from the literature; the data was gathered initially by close-ended interviews conducted with a panel of twelve experts followed by a well-structured questionnaire. Structural Equation Modeling (SEM) was employed via AMOS to analyze the data and construct a model representing the intricate relationships between the processes. Additionally, the validity and reliability of the method were inspected.FindingsThe data analysis confirmed that PIM and PCmM were correlated according to contractors and consultants in the Jordanian construction industry. Furthermore, both have a positive influence on the PRiM. In addition, a 13-step process was developed to apply extra processes and practices to ensure better implementation of the PRiM in developing countries.Originality/valueThe literature highlights that integration and communication management influence project performance. However, there is a lack of research utilizing practices from these knowledge areas to achieve better project risk management implementation. This research highlights two of the most underrated knowledge areas in project management. Therefore, a framework was devised, comprising processes that practitioners should take into account during the planning phase leading to efficient PRiM to enhance their managerial proficiency.
Uniqlo in Russia: market exit dilemma in an international market
Authors: Singh Harvinder 
Published: August 2024

Learning outcomes
After completion of the case study, students will be able to: 1. understand the basis for developing global supply chains for exploring international markets, 2. identify the various sources of geopolitical risk while expanding globally, 3. assess the market entry or exit decisions from a principled and commercial perspective and 4. identify and weigh different options when faced with an exit situation under conditions of geopolitical risk.

Case overview/synopsis
The Japanese fast fashion brand Uniqlo opened 45 stores in Russia as a part of its international retail expansion strategy. The brand provided affordable fashion for everyone. However, the Russia–Ukraine armed conflict had put the company in a dilemma. The Japanese Government and the public joined the broader global community in condemning Russia’s armed intervention in Ukraine. These countries also imposed economic sanctions on Russia, resulting in many multinational companies winding up their operations in Russia. Uniqlo faced a market exit dilemma. Russia had the largest number of Uniqlo stores in Europe. The company CEO also highlighted the necessity of meeting the clothing needs of the Russian people. However, people in Japan and elsewhere considered Russia as an aggressor nation. Any economic link with the Russian market would be ethically wrong, and consumers in Japan, the USA and the European Union might see this as support for Russia’s war efforts. The company had to choose between continuing operations in Russia or exiting the Russian market.

Complexity academic level
This case study can be used in basic marketing management and international business courses to discuss the market attractiveness and risk aspects for market entry or exit decisions. It can also be used in advanced courses such as strategic management, global strategy and global political economy, highlighting the impact of geopolitical conflicts on business operations.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.