bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and safety of a monovalent Omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine in previously unvaccinated, SARS-CoV-2 seropositive participants: primary day-28 analysis of a phase 2/3 open-label study
Authors: Alves Katia , Kouassi Alex , Plested Joyce S. , Kalkeri Raj , Smith Katherine , Kaba Muneer , Nelson Joy , Zhu Mingzhu , Cloney-Clark Shane , Cai Zhaohui , Mallory Raburn M. , Noriega Fernando 
Published: November 2024

SummaryBackgroundMost of the population has been infected with SARS-CoV-2 and, thus, is primed by natural exposure. As such, it was assessed whether a single dose of the monovalent XBB.1.5 vaccine, NVX-CoV2601, elicited a comparable immune response to XBB.1.5 in seropositive unvaccinated participants to that in previously vaccinated participants, thereby allowing the former to forego a two-dose primary series.MethodsIn this phase 2/3, open-label, single-arm study (2019nCoV-313/NCT05975060[part 2]), vaccine-naive participants ≥18 years with previous SARS-CoV-2 infection received one dose of NVX-CoV2601. This analysis compared the 28-day immunogenicity and safety of NVX-CoV2601 in vaccine-naive and previously vaccinated (≥3 prior mRNA-based vaccines, from 2019nCoV-313 part 1) participants.Noninferiority of neutralizing antibody (nAb) response in vaccine-naive versus vaccinated participants was the primary objective. The day-28 geometric mean titer (GMT) ratio (GMTR) and seroresponse rate (SRR; percentage of participants with a ≥4-fold rise in antibody response from baseline) were measured, and safety was assessed.ResultsOf the participants enrolled from September 11–November 15, 2023, per-protocol sets included 306/338 (90.5%) vaccine-naive and 309/332 (93.1%) vaccinated participants. At day 28, adjusted GMTs (95% CI) against XBB.1.5 in the vaccine-naive and vaccinated groups were 1491.5 (1277.5–1741.4) and 841.4 (723.9–978.0), respectively. The vaccine-naïve—vaccinated nAb GMTR was 1.8 (95% CI 1.43–2.20) and SRRs were 74.3% and 64.3% for vaccine-naive and vaccinated participants, respectively (SRR difference: 10.0 [95% CI 2.6–17.4]). No new safety signals or events of special interest were reported.ConclusionsA single dose of NVX-CoV2601 in vaccine-naive participants with a history of SARS-CoV-2 infection elicited a robust neutralizing antibody response that was noninferior to that observed in vaccinated participants. The vaccine was well-tolerated. These data support the use of NVX-CoV2601 as a single dose, regardless of prior vaccination history.Trial registration:NCT05975060
Trend Analysis on the Application of Social Work Professionalism: The Case of Refugee Child-Focused Humanitarian Organizations in Ethiopia
Authors: Afework Fisehatsion , Mengsteab Mesele 
Published: November 2024

AbstractThis study investigated the trend in the application of social work professionalism in delivering child-focused social work services for refugee children within Ethiopian refugee camps. The study seeks to understand the how the various constituents of social work professionalism has been applied by child-focused humanitarian organizations between the years of 2017 to 2023. A time series trend analysis model employed along with a mixed-methods approach across three refugee camps selected through multi-stage cluster sampling. The research investigates how social work services align with professional standards and the challenges faced by practitioners. Findings reveal significant caseloads, resource constraints, and ethical dilemmas in service prioritization. However, positive trends emerge, including the implementation of the Child Protection Minimum Standards framework, a client-centered approach, and growing collaboration with the families of refugee children. The study translates these findings into actionable recommendations for strengthening social work practice, including increased funding, caseload management strategies, prioritizing child participation, and fostering inter-agency collaboration. A proposed model generated through the study visually depicts key challenges, positive trends, and recommendations to improve child-focused social work services through the lens of professional ethics in refugee settings. This research underscores the importance of a multi-pronged approach to ensure high-quality, ethical services for all refugee children.
A Comprehensive and Robust Multiplex-DIA Workflow Profiles Protein Turnover Regulations Associated with Cisplatin Resistance
Authors: Salovska Barbora , Li Wenxue , Bernhardt Oliver M. , Germain Pierre-Luc , Gandhi Tejas , Reiter Lukas , Liu Yansheng 
Published: November 2024

SummaryMeasuring protein turnover is essential for understanding cellular biological processes and advancing drug discovery. The multiplex DIA mass spectrometry (DIA-MS) approach, combined with dynamic SILAC labeling (pulse-SILAC, or pSILAC), has proven to be a reliable method for analyzing protein turnover and degradation kinetics. Previous multiplex DIA-MS workflows have employed various strategies, including leveraging the highest isotopic labeling channels of peptides to enhance the detection of isotopic MS signal pairs or clusters. In this study, we introduce an improved and robust workflow that integrates a novel machine learning strategy and channel-specific statistical filtering, enabling dynamic adaptation to systematic or temporal variations in channel ratios. This allows comprehensive profiling of protein turnover throughout the pSILAC experiment without relying solely on the highest channel signals. Additionally, we developedKdeggeR, a data processing and analysis package optimized for pSILAC-DIA experiments, which estimates and visualizes peptide and protein degradation rates and dynamic profiles. Our integrative workflow was benchmarked on both 2-channel and 3-channel standard DIA datasets and workflow to an aneuploid cancer cell model before and after cisplatin resistance development demonstrated a strong negative correlation between transcript regulation and protein degradation for major protein complex subunits. We also identified specific protein turnover signatures associated with cisplatin resistance.
APOBEC3A, not APOBEC3B, drives deaminase mutagenesis in human gastric epithelium
Authors: An Yohan , Lee Ji-Hyun , Lim Joonoh , Youk Jeonghwan , Park Seongyeol , Park Ji-Hyung , Yi Kijong , Kim Taewoo , Nam Chang Hyun , Lee Won Hee , Oh Soo A , Bae Yoo Jin , Lee Junehwak , Park Jung Woo , Kim Jie-Hyun , Kim Hyunki , Snippert Hugo , Koo Bon-Kyoung , Ju Young Seok 
Published: November 2024

AbstractCancer genomes frequently carry APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like)-associated DNA mutations, suggesting APOBEC enzymes as innate mutagens during cancer initiation and/or evolution. However, the pure mutagenic impacts of the specific enzymes among this family that are responsible for APOBEC-associated mutagenesis remain unclear, particularly the comparative mutagenic activities ofAPOBEC3AandAPOBEC3B. Here, we investigated the mutagenic contributions of these enzymes through whole-genome sequencing of human normal gastric organoid lines carrying doxycycline-inducibleAPOBEC3AorAPOBEC3Bcassettes. Our findings demonstrated that transcriptionalAPOBEC3Aupregulation led to the acquisition of a massive number of genomic mutations in a few cell cycles. By contrast,APOBEC3Bupregulation did not generate a substantial number of mutations in gastric epithelium.APOBEC3B-associated mutagenesis remained insignificant even after a combined inactivation ofTP53. Based on the spectrum of acquired mutations afterAPOBEC3Aupregulation, we further analyzedAPOBEC3A-associated mutational signatures, encompassing indels mainly composed of 1bp deletions, characteristics of clustered mutations, and selective pressures operative on cells carrying the mutations. Our observations provide a clear foundation for understanding the mutational impact of APOBEC enzymes in human cells.
Potential impact of a population-based screening program on the increased burden of prostate cancer in Thailand: A simulation study
Authors: Alvarez Christian S. , Mondul Alison M. , Rozek Laura S. , Sriplung Hutcha , Meza Rafael , Jeon Jihyoun 
Published: November 2024

AbstractBackgroundProstate cancer incidence and mortality are expected to increase considerably in the near future in Thailand. There is thus an urgent need to establish prevention measures, such as screening, to reduce the increasing burden of prostate cancer in Thailand.MethodsUsing data from several sources including the Songkhla Cancer Registry and the census data from Thailand, we conducted a simulation analysis to assess the potential impact of screening on the incidence and mortality of prostate cancer among 10 million males aged 50 to 70 of 1960 birth cohort from Songkhla, Thailand. We assumed 4 different scenarios, including no screening, 15%, 60% and 100% screening uptakes of the prostate-specific antigen test. Furthermore, stage distribution of prostate cancer was assumed based on two major prostate cancer screening trials: European Randomized Study of Screening for Prostate Cancer (ERSPC) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The number of prostate cancer cases was projected using an age-period-cohort model approach, accounting for the expected excess of cases due to screening. Deaths from prostate cancer were then projected using survival probabilities from Songkhla and the United States. Case fatality ratios (CFRs) were also computed.ResultsProstate cancer incidence increased with screening, as expected, with a shift of the stage distribution toward earlier stages, but mortality from prostate cancer decreased with higher screening uptake. Assuming 1.71 excess risk of cases due to screening and stage distribution from the ERSPC trial, we projected an increase of over 7,000 localized cases under 100% screening uptake, while the cases in advanced stages decreased from 4,046 (no screening) to 96 under 100% screening uptake. The number of deaths were reduced by 82% under 100% screening uptake compared to no screening. The CFR also decreased from 0.42 (no screening) to 0.05 (100% screening).ConclusionScreening for prostate cancer could substantially reduce the number of prostate cancer cases in advanced stages and prostate cancer deaths. Although the net benefit depends on the assumed survival rates under screening, which could vary depending on the quality of the implementation, screening would contribute to reducing the escalating burden of prostate cancer in Thai population.
REDD1 is a determinant of the sensitivity of renal cell carcinoma cells to autophagy inhibition that can be therapeutically exploited by targeting PIM kinase activity
Authors: Carew Jennifer S. , Espitia Claudia M. , Sureshkumar Sruthi , Espinoza Maria Janina Carrera , Gamble Madison E. , Wang Wei , Lee Benjamin R. , Nawrocki Steffan T. 
Published: November 2024

AbstractPurposeRepurposing FDA approved drugs with off-target autophagy inhibition such as chloroquine/hydroxychloroquine (CQ, HCQ) has produced modest anticancer activity in clinical trials, due in part, to a failure to define predictive biomarkers that enable the selection of patients that best respond to this treatment strategy. We identified a new role for REDD1 as a determinant of sensitivity to autophagy inhibition in renal cell carcinoma (RCC).Experimental DesignRNA sequencing, qRT-PCR, immunoblotting, gene silencing, knockout and overexpression studies revealed that REDD1 expression is a key regulator of cell death stimulated by autophagy inhibitors. Comprehensivein vitroandin vivostudies were conducted to evaluate the selectivity, tolerability, and efficacy of the PIM kinase inhibitor TP-3654 and CQ in preclinical models of renal cell carcinoma (RCC). Markers of autophagy inhibition and cell death were evaluated in tumor specimens.ResultsTranscriptomic analyses identified REDD1 (DDIT4) as a highly induced gene in RCC cells treated with the PIM kinase inhibitor TP-3654. Focused studies confirmed that PIM1 inhibition was sufficient to induce REDD1 and stimulate autophagy through the AMPK cascade.DDIT4knockout and overexpression studies established its mechanistic role as a regulator of sensitivity to autophagy inhibition. Inhibition of autophagy with CQ synergistically enhanced the in vitroandin vivoanticancer activity of TP-3654.ConclusionsOur findings identify REDD1 as a novel determinant of the sensitivity of RCC cells to autophagy inhibition and support further investigation of PIM kinase inhibition as a precision strategy to drive sensitivity to autophagy-targeted therapies through REDD1 upregulation.Translational RelevancePIM kinases are overexpressed in renal cell carcinoma (RCC) and other malignancies. Here we show that targeting PIM1 significantly upregulates REDD1/DDIT4expression, resulting in inhibition of mTOR and autophagy activation. REDD1 induction was determined to be a major factor that regulates the sensitivity of RCC cells to autophagy inhibition. Comprehensivein vitroandin vivostudies in preclinical models of RCC demonstrated that the PIM kinase inhibitor TP-3654 induced REDD1-mediated autophagy and synergistically sensitized cells to autophagy inhibition. Our findings define a new role for REDD1 as a determinant of the sensitivity of RCC cells to autophagy inhibition and demonstrate that antagonizing PIM kinase activity is a precision approach to augment REDD1 levels and potentiate the therapeutic benefit of targeting the autophagy pathway.
The limited capacity of bioaerosols to serve as cloud-condensation nuclei may restrict their potential to initiate ice formation in mixed-phase clouds
Authors: Šantl-Temkiv Tina , Živec Miha , Lund Marie Braad , Benčina Mojca , Bohn Anja Bille , Stanič Samo , Močnik Griša 
Published: November 2024

AbstractBioaerosols are gaining prominence due to their ability to nucleate ice in clouds at high subzero temperatures, thereby impacting cloud characteristics, and longevity. Acting first as cloud condensation nuclei (CCN) and second as ice nucleating particles, bioaerosols induce ice formation through immersion freezing. Nevertheless, insights into bioaerosol ability to act as CCNin situare currently lacking. We simultaneously collected bioaerosols from the condensed and interstitial phase of clouds using size selective inlets during autumn 2020 from the Otlica observatory (Slovenia). With a polarization Raman Lidar, we confirmed the coexistence of ice particles and liquid droplets during one of the three sampling campaigns. Using spectral flow cytometers, the PINGUIN cold-stage setup and MiSeq-facilitated amplicon sequencing to assess bacterial and fungal communities, we found that both bioaerosols and biogenic ice-nucleating particles were significantly more abundant in the interstitial phase compared to the condensed phase, suggesting that they were poor CCN, unable to compete with more hygroscopic particles. Most taxa did not exhibit preferential partitioning, suggesting that surface properties generally did not significantly influence their behaviour as CCN. Our results underline the need to systematically investigate the relation between hygroscopicity and ice-nucleating activity of bioaerosols to understand theirin-situeffects on cloud formation.SynopsisThe relationship between the ability of bioaerosols to nucleate cloud droplets and ice particles has not been determined. This study found that bioaerosols are poor cloud condensation nuclei which may impair their ability to nucleate ice and affect cloud formation and climate.
Physical-aware model accuracy estimation for protein complex using deep learning method
Authors: Wang Haodong , Sun Meng , Xie Lei , Liu Dong , Zhang Guijun 
Published: November 2024

AbstractWith the breakthrough of AlphaFold2 on monomers, the research focus of structure prediction has shifted to protein complexes, driving the continued development of new methods for multimer structure prediction. Therefore, it is crucial to accurately estimate quality scores for the multimer model independent of the used prediction methods. In this work, we propose a physical-aware deep learning method, DeepUMQA-PA, to evaluate the residue-wise quality of protein complex models. For the input complex model, the residue-based contact area and orientation features were first constructed using Voronoi tessellation, representing the potential physical interactions and hydrophobic properties. Then, the relationship between local residues and the overall complex topology as well as the inter-residue evolutionary information are characterized by geometry-based features, protein language model embedding representation, and knowledge-based statistical potential features. Finally, these features are fed into a fused network architecture employing equivalent graph neural network and ResNet network to estimate residue-wise model accuracy. Experimental results on the CASP15 test set demonstrate that our method outperforms the state-of-the-art method DeepUMQA3 by 3.69% and 3.49% on Pearson and Spearman, respectively. Notably, our method achieved 16.8% and 15.5% improvement in Pearson and Spearman, respectively, for the evaluation of nanobody-antigens. In addition, DeepUMQA-PA achieved better MAE scores than AlphaFold-Multimer and AlphaFold3 self-assessment methods on 43% and 50% of the targets, respectively. All these results suggest that physical-aware information based on the area and orientation of atom-atom and atom-solvent contacts has the potential to capture sequence-structure-quality relationships of proteins, especially in the case of flexible proteins. The DeepUMQA-PA server is freely available athttp://zhanglab-bioinf.com/DeepUMQA-PA/.
Transmembrane domains of H1 and H3 hemagglutinin contribute to membrane fusion in a different manner
Authors: Borkowska Paulina , Kubiszewski-Jakubiak Szymon , Bykowski Michał , Kowalewska Łucja , Michalski Michał , Setny Piotr , Worch Remigiusz 
Published: November 2024

AbstractHemagglutinin (HA), a fusion protein of influenza virus, has been extensively researched as a model fusion viral protein. However, most of the efforts focus on the fusion peptide (FP) and the ectodomain, while relatively little is known about the “membrane anchor”, a transmembrane domain (TMD). While the structural insights on H1 subtype full-length HA underlay the influence of TMD on the ectodomain orientations, the structures representing the other phylogenetic group are still unavailable. Inspired by the sequential varieties of TMDs in both groups, we performed a series of experiments on full-length HA proteins with H1and H3-swapped TMD domains in virus-like particles (VLP). In parallel, we studied the behaviour an and interplay of FP and TMD-corresponding fragments with the use of artificial membrane systems and molecular dynamics simulations. We detect clearly a distinct interplay between FP and TMDs in the two phylogenetic groups. We observe that TMD-dependent fusion activity originates from TMD-lipid interactions, but not direct FP:TMD complexing.
Parallel cases of ring speciation within a rapid adaptive radiation of cichlid fishes
Authors: Gautier Grégoire , Mahulu Anna , Seehausen Ole , Singh Pooja 
Published: November 2024

ABSTRACTRing species provide a valuable framework for studying intermediate steps of speciation resulting in two new species. Classic examples of ring species have involved large spatial and temporal scales – and this is partly why few idealised cases exist. In contrast, we focus on two species complexes of cichlid fishes from Southern Lake Victoria that evolved rapidly within the last 15,000 years across relatively small geographic space. We reconstruct the path to speciation between two forms ofPundamiliaandNeochromisspecies that exist in a ring-like distribution around deep water, which acts as a dispersal barrier for these shallow water adapted fishes. We test key predictions of ring-like biogeography, population connectivity, terminal overlap and differentiation in mating and ecological traits. Our results indicate that both species complexes show a gradual change in craniofacial morphology along a ring-like distribution, corresponding to diet shifts. This phenotypic change is correlated with geographical distance in both rings, although they appear to have spatially different evolutionary trajectories. Sympatric species at the ends of both rings exhibit signs of convergent and divergent ecological character displacement in several craniofacial traits, potentially explaining their coexistence. In contrast to craniofacial morphology, male nuptial colouration changes abruptly in both rings, with the change occurring at the end of the ring inPundamiliaand early inNeochromis. We discuss the influence of environmental factors on the observed phenotypic variation and how resistance to connectivity might alter the isolation-by-distance pattern. Our study provides compelling evidence of how concerted changes in mating and ecological traits during isolation by distance can lead to new species and highlights the importance of parapatric speciation in adaptive radiation.
A systematic review on mediators and moderators of job insecurity–health relation before and after COVID-19 pandemic
Authors: Charkhabi Morteza , Radi Afsouran Naghi , Johnson Laura K. , Dutheil Frédéric 
Published: November 2024

PurposeJob insecurity is one of the most hazardous work stressors in the twenty-first century, placing employees between employment and unemployment may threaten employees’ health in the workplaces. Using a systematic review, the first aim of this study is to list the mediators and moderators of the link between job insecurity and health-related outcomes, and second, to explain and discuss the mechanisms that could explain the mediating and moderating effects.Design/methodology/approachWe searched four databases (Science Direct, PubMed, Springer Link and Google Scholar) from 2008 to 2018 to detect these mediators and moderators. Also, as the study was conducted during COVID-19 pandemic, we particularly searched and reported the same associations over this period (2019–2022).FindingsThe results of the review suggest that job insecurity negatively influences a wide range of both health- and safety-related outcomes in the workplace. The results also showed that the most studied mediator and moderator of the job insecurity-health link over the past 10 years has been workload and employability. During COVID-19, the number of studies on mediators were more than moderators and coping strategies appeared to gain more research attention. Additionally, this review suggests that, to explain the mediation and moderation effects, a combination of cognitive appraisal theory and the conservation of resources theory can be used.Originality/valueAlthough this review suggests that job insecurity detrimentally influences employee health, the severity of this impact on health-related outcomes may vary by the effects of various moderators.