bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vibrio cholerae
pathogenicity island 2 encodes two distinct types of restriction systems
Authors: Vizzarro Grazia , Lemopoulos Alexandre , Adams David William , Blokesch Melanie 
Published: August 2024

ABSTRACT

In response to predation by bacteriophages and invasion by other mobile genetic elements such as plasmids, bacteria have evolved specialized defense systems that are often clustered together on genomic islands. The O1 El Tor strains of
Vibrio cholerae
responsible for the ongoing seventh cholera pandemic (7PET) contain a characteristic set of genomic islands involved in host colonization and disease, many of which contain defense systems. Notably,
Vibrio
pathogenicity island 2 contains several characterized defense systems as well as a putative type I restriction-modification (T1RM) system, which, interestingly, is interrupted by two genes of unknown function. Here, we demonstrate that the T1RM system is active, methylates the host genomes of a representative set of 7PET strains, and identify a specific recognition sequence that targets non-methylated plasmids for restriction. We go on to show that the two genes embedded within the T1RM system encode a novel two-protein modification-dependent restriction system related to the GmrSD family of type IV restriction enzymes. Indeed, we show that this system has potent anti-phage activity against diverse members of the
Tevenvirinae
, a subfamily of bacteriophages with hypermodified genomes. Taken together, these results expand our understanding of how this highly conserved genomic island contributes to the defense of pandemic
V. cholerae
against foreign DNA.

IMPORTANCE

Defense systems are immunity systems that allow bacteria to counter the threat posed by bacteriophages and other mobile genetic elements. Although these systems are numerous and highly diverse, the most common types are restriction enzymes that can specifically recognize and degrade non-self DNA. Here, we show that the
Vibrio
pathogenicity island 2, present in the pathogen
Vibrio cholerae
, encodes two types of restriction systems that use distinct mechanisms to sense non-self DNA. The first system is a classical Type I restriction-modification system, and the second is a novel modification-dependent type IV restriction system that recognizes hypermodified cytosines. Interestingly, these systems are embedded within each other, suggesting that they are complementary to each other by targeting both modified and non-modified phages.
Abrupt structural deformation changes from the boundary to the interior of a craton basin: Implications for the long-term stability of cratonic blocks
Authors: Huang Lei , Liu Chiyang , Wang Zhao , Zhou Yijun , Liu Yongtao , Li Xin , Yang Lihua 
Published: August 2024

Abstract
Stable intraplate cratonic blocks usually have less structural deformation and fewer earthquakes than other locations on Earth, but with strong compressional deformation around their periphery. Investigating how and why this different deformation occurred is beneficial for understanding why the cratonic block is so stable and how the intraplate in-plane stress is transmitted. In this work, we first investigated the structural deformation changes from the margin to the interior of the western Ordos block (one of the most tectonically stable areas in China) via seismic data. The results show abrupt structural deformation changes from the margin to the interior of the Ordos block in terms of the deformation strength (from strong to weak), structural orientation (high-angle oblique relationships), and kinematics (from compression to wrenching). Our investigation also shows that such phenomena are widespread in cratonic blocks worldwide. The abrupt changes are probably induced by special in-plane stress transfer inside the cratonic block: When far-field stress is transmitted into continental interiors from active plate margins, the weak belt around the cratonic block filters and accommodates the in-plane stress. Consequently, this decreases the stress, changes the stress direction, and transmits the in-plane stress along a shallower layer (probably less than 1500 m). Furthermore, the compressional stress from the plate margin is converted into shear stress within the cratonic block. This stress transmission manner makes reactivation of deep preexisting faults difficult under far-field horizontal plate-boundary stresses in the cratonic block without vertical forces from the mantle, guaranteeing long-term stability and low seismicity. This understanding can provide a new perspective for the interpretation of earthquakes in stable continental regions. It can also be applied to appraise the long-term stability of sites for the storage of CO2.
Long-term retention and positive deviant practices in Uganda’s community client-led antiretroviral distribution groups (CCLADs): a mixed-methods study
Authors: Natukunda Julian , Baleeta Keith , Kiriya Junko , Ong Ken Ing Cherng , Carandang Rogie Royce , Muhwezi Augustin , Shibanuma Akira , Jimba Masamine 
Published: August 2024

BackgroundHIV testing and starting antiretroviral therapy (ART) are pivotal in treating people living with HIV (PLHIV) but sustaining PLHIV on treatment remains challenging. We assessed retention and attrition in community client-led antiretroviral distribution groups (CCLADs) in Uganda and identified positive deviant practices that foster long-term retention.MethodsUsing explanatory mixed methods, we collected longitudinal medical data from 65 health facilities across 12 districts in East Central Uganda. Quantitative phase, from 18 April 2021 to 30 May 2021, employed survival analysis and Cox regression to assess retention and identify attrition risk factors. Qualitative inquiry focused on four districts with high attrition from 11 August 2021 to 20 September 2021, where we identified nine health facilities exhibiting high retention in CCLADs. We purposively selected 50 clients for in-depth interviews (n=22) or focus group discussions (n=28). Using thematic analysis, we identified positive deviant practices. We integrated quantitative and qualitative findings into joint displays.ResultsInvolving 3055 PLHIV, the study showed retention rates of 97.5% at 6 months, declining to 89.7% at 96 months. Attrition risk factors were lower levels of care (health centre three (adjusted HR (aHR) 2.80, 95% CI 2.00 to 3.65) and health centre four (aHR 3.61, 95% CI 2.35 to 5.54)); being unemployed (aHR 2.21, 95% CI 1.00 to 4.84); enrolment year into CCLAD (aHR 23.93, 95% CI 4.66 to 123.05) and virological failure (aHR 3.41, 95% CI 2.51 to 4.63). Of 22 clients interviewed, 8 were positive deviants. Positive deviants were characterised by prolonged retention in CCLADs, improved clinical outcomes and practised uncommon behaviours that enabled them to find better solutions than their peers. Positive deviant practices included fostering family-like settings, offering financial or self-development advice, and promoting healthy lifestyles.ConclusionsFindings underscore the importance of addressing factors contributing to attrition and leveraging positive deviant practices to optimise retention and long-term engagement in HIV care.
Cancer burden across the South Asian Association for Regional Cooperation in 2022
Authors: Jain Urvish , Rahim Faraan , Jain Bhav , Komanduri Abhinav , Arkalgud Aditya , Sabet Cameron John , Hammond Alessandro , Tshering Phub , Patel Tej A , Sirohi Bhawna , Jain Pankaj , Khan Shah Zeb , Gunasekera Sanjeeva , Shilpakar Ramila , Stanikzai Zabihullah , Chowdhury Arman Reza , Swami Nishwant , Dee Edward Christopher , Gyawali Bishal 
Published: August 2024

ObjectiveThe objective of this study is to present a cross-sectional analysis of cancer burden in the South Asian Association for Regional Cooperation (SAARC) region and explain unique characteristics of its cancer burden as compared with the rest of the world.Methods and analysisUsing publicly available data from the Global Cancer Observatory (GCO) and the World Bank, we collected cancer statistics and population statistics for Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka from 2017 to 2022.ResultsThe number of newly diagnosed cases in the region was 1 846 963, representing 9.3% of the incidence worldwide. As defined by the GCO, the crude incidence rate (CIR) (per 100 000) of cancer in SAARC was 97.3 compared with the worldwide rate of 235.5. The crude mortality rate (per 100 000) in SAARC was 63.4, compared with 123.6 globally. However, the mortality to incidence ratio (MIR) (per 100 000) was 0.65, compared with 0.49 globally.ConclusionOur research highlights SAARC’s unique cancer landscape with low incidence (CIR) and mortality (CMR) but elevated MIR compared with global figures. These findings underscore the need for a united, contextually relevant approach to addressing the burden of cancer in SAARC. In particular, investment in collaborative, tailored cancer care programmes will build the SAARC region’s capacity to address the growing cancer challenge.
Five-year follow-up of neoadjuvant PD-1 inhibitor (sintilimab) in non-small cell lung cancer
Authors: Zhou Bolun , Zhang Fan , Guo Wei , Wang Shuhang , Li Ning , Qiu Bin , Zhao Liang , Li Jian , Shao Kang , Xue Qi , Lv Fang , Gao Shugeng 
Published: August 2024

BackgroundNeoadjuvant anti-programmed cell death protein-1 (PD-1) therapy exhibits potential in treating resectable non-small cell lung cancer (NSCLC). Previously, we have reported the 3-year clinical outcomes of this trial, implying the effectiveness and feasibility of neoadjuvant sintilimab monotherapy. However, the long-term prognosis of patients receiving neoadjuvant mono-immunotherapy has yet to be elucidated.MethodsFor patients with stage IA-IIIB NSCLC, two doses of sintilimab (200 mg) were administered intravenously in the neoadjuvant setting. The 5-year event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were assessed in these updated results. The predictive role of specific biomarkers in neoadjuvant immunotherapy was also explored.ResultsWith a median follow-up of 61.0 months, 5-year DFS and OS rates of patients who underwent R0 resection were 65.7% and 80.4%, respectively. The 5-year DFS and OS rates of patients with positive programmed death-ligand 1 (PD-L1) expression were 71.9% and 90.9%, respectively. The presence of PD-L1 positivity (tumor proportion score ≥1%) showed a tendency toward the promising prognosis (OS, HR, 0.143; 95% CI: 0.027 to 0.743), especially for those who did not achieve pathological complete response (pCR). In addition, tumor mutation burden was positively correlated with a favorable prognosis. A total of 10 recurrences and 5 subsequent deaths were identified within the 5-year follow-up, with lung metastasis being the predominant.ConclusionsThese updated analyses were the first to unveil the 5-year survival benefits of neoadjuvant sintilimab monotherapy, implying the potential value of PD-1 inhibitors in neoadjuvant therapy.
Supply and demand effects between tobacco retailer density and smoking prevalence
Authors: Golden Shelley D , Kuo Tzy-Mey , Combs Todd , Kong Amanda Y , Ribisl Kurt M , Baggett Chris D 
Published: August 2024

ObjectivePlaces with more tobacco retailers have higher smoking prevalence levels, but whether this is because retailers locate where people who smoke live or whether tobacco availability prompts tobacco use is unknown. In this study, we compare the role of consumer demand with that of tobacco supply in longitudinal, area-based associations of tobacco retailer density with smoking prevalence.MethodsWe merged annual adult smoking prevalence estimates derived from the USA Behavioural Risk Factor Surveillance System data with annual county estimates of tobacco retailer density calculated from the National Establishment Time Series data for 3080 counties between 2000 and 2010. We analysed relationships between retailer density and smoking in 3080 counties, using random intercept cross-lagged panel models and employing two measures of tobacco retailer density capturing the number of likely tobacco retailers in a county divided by either the population or land area.ResultsBoth density models provided evidence of significant demand and supply effects; in the population-based model, the association of smoking prevalence in 1 year with tobacco retailer density in the next year (standardised coefficient=0.038, p<0.01) was about double the association between tobacco retailer density with subsequent smoking prevalence (0.017, p<0.01). The reverse was true in the land area-based model, where the supply effect (0.042, p<0.01) was more than 10 times stronger than the demand effect (0.003, p<0.01).ConclusionsPolicies that restrict access to retail tobacco have the potential to reduce smoking prevalence, but pairing such policies with interventions to reduce consumer demand remains important.
Rotational influence on fermions within negative curvature wormholes
Authors: Guvendi Abdullah , Gurtas Dogan Semra , Vitória R. L. L. 
Published: August 2024

AbstractIn this research, we examine relativistic fermions within the rotating frame of negative curvature wormholes. Initially, as is typical in our context, we introduce the wormholes by embedding a curved surface into a higher-dimensional flat Minkowski spacetime. Subsequently, we derive the spacetime metric that characterizes the rotating frame of these wormholes. We then investigate analytical solutions of the generalized Dirac equation within this framework. Through exploring a second-order non-perturbative wave equation, we seek exact solutions for fermions within the rotating frame of hyperbolic and elliptic wormholes, also known as negative curvature wormholes. Our analysis provides closed-form energy expressions, and we generalize our findings to Weyl fermions. By considering the impact of the rotating frame and curvature radius of wormholes, we discuss how these factors affect the evolution of fermionic fields, offering valuable insights into their behavior.
Breast, Colorectal, and Prostate Cancer Incidence among Filipino Americans by Generational Status in the Multiethnic Cohort Study
Authors: Abe Janine V. , Legaspi Justin , Guillermo Cherie , Bogumil David , Setiawan Veronica Wendy , Le Marchand Loïc , Hernandez Brenda Y. , Wilkens Lynne R. , Maskarinec Gertraud 
Published: August 2024

Abstract

Background:
Filipino Americans constitute 12% and 4% of the respective populations of Hawaii and California, with a large proportion of immigrants experiencing increasing cancer rates. This study investigated the incidence of colorectal, breast, and prostate cancers by generational status in the Multiethnic Cohort.

Methods:
We analyzed 10,495 Filipino Multiethnic Cohort first-, second-, and third-generation participants, in which 26.8% were of mixed race and ethnicity. Linkage to statewide cancer registries identified 375 breast, 249 colorectal, and 436 prostate cancer incident cases. Cox models were used to calculate HRs and 95% confidence intervals (CI) for the association between generational status and cancer incidence. Models were adjusted for age at cohort entry and cancer-specific covariates that were chosen based on stepwise regression.

Results:
Compared with the first generation, colorectal cancer showed a significantly higher incidence in the second and third generations with respective HRs of 1.43 (95% CI, 1.04, 1.98) and 1.76 (95% CI, 1.29, 2.38). This association was attenuated after adjustment for relevant covariates. Breast cancer incidence was elevated in the third versus first generation (HR = 1.29; 95% CI, 1.01, 1.63) even in the fully adjusted model, whereas little difference was observed for prostate cancer.

Conclusions:
In this prospective study, we found differences in incidence by generational status, specifically colorectal cancer among men and female breast cancer.

Impact:
Understanding behavioral changes due to acculturation is warranted to mitigate cancer risks in migrant populations.
Endovascular Thrombectomy Alone for Large Vessel Occlusion: A Cost-Effectiveness Evaluation Based on Meta-Analyses
Authors: Nguyen Chi Phuong , Lahr Maarten M.H. , van der Zee Durk-Jouke , Rinkel Leon A. , van Voorst Henk , Pinckaers Florentina M.E. , Cavalcante Fabiano , LeCouffe Natalie E. , Kappelhof Manon , Treurniet Kilian M. , Coutinho Jonathan M. , Majoie Charles B.L.M. , Roos Yvo B.W.E.M. , Buskens Erik , Uyttenboogaart Maarten ,   on behalf of the CONTRAST Consortium
Published: August 2024

BACKGROUND:
The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective.

METHODS:
A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses.

RESULTS:
Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52 500 and $84 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52 500 threshold, and 79%, 91%, and 67% of simulations at the $84 000 threshold.

CONCLUSIONS:
Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52 500 threshold but possibly cost-effective at the $84 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT.
Metoclopramide to Prevent Pneumonia in Patients With Stroke and a Nasogastric Tube: Data From the PRECIOUS Trial
Authors: Sluis Wouter M. , de Jonge Jeroen C. , Reinink Hendrik , Woodhouse Lisa J. , Westendorp Willeke F. , Bath Philip M. , van de Beek Diederik , van der Worp H. Bart ,   for the PRECIOUS Investigators
Published: August 2024

BACKGROUND:
A randomized trial suggested that treatment with metoclopramide reduces the risk of pneumonia in patients with acute stroke and a nasogastric tube. We assessed whether this finding could be replicated in a post hoc analysis of the randomized PRECIOUS trial (Prevention of Complications to Improve Outcome in Elderly Patients With Acute Stroke).

METHODS:
PRECIOUS was an international, 3×2 partial-factorial, randomized controlled, open-label clinical trial with blinded outcome assessment assessing preventive treatment with metoclopramide, paracetamol, and ceftriaxone in patients aged ≥66 years with acute ischemic stroke or intracerebral hemorrhage and a National Institutes of Health Stroke Scale score ≥6. In the present study, we analyzed patients who had a nasogastric tube within 24 hours after randomization. Patients who were allocated to metoclopramide (10 mg TID) were compared with patients who were not. Treatment was started within 24 hours after symptom onset and continued for 4 days or until discharge if earlier. The primary outcome was pneumonia in the first week after stroke. The score on the modified Rankin Scale after 90 days was a secondary outcome and analyzed with ordinal logistic regression.

RESULTS:
From April 2016 through June 2022, a total of 1493 patients were enrolled with 1376 included in this analysis, of whom 1185 (86%) had ischemic stroke and 191 (14%) had intracerebral hemorrhage. The first day after randomization, 329 (23.9%) patients had a nasogastric tube, of whom 156 were allocated to metoclopramide and 173 to standard care. Metoclopramide was not associated with a reduction of pneumonia (41.0% versus 35.8%; adjusted odds ratio, 1.35 [95% CI, 0.79–2.30]) or with poor functional outcome (adjusted odds ratio, 1.07 [95% CI, 0.71–1.61]).

CONCLUSIONS:
In patients with stroke who had a nasogastric tube shortly after stroke onset, metoclopramide for 4 days did not reduce pneumonia or have an effect on the functional outcome.
Atmospheric Moisture Decreases Midlatitude Eddy Kinetic Energy
Authors: Lutsko Nicholas J. , Martinez-Claros José , Koll Daniel D. B. 
Published: August 2024

Abstract
There is compelling evidence that atmospheric moisture may either increase or decrease midlatitude eddy kinetic energy (EKE). We reconcile these findings by using a hierarchy of idealized atmospheric models to demonstrate that moisture energizes individual eddies given fixed large-scale background winds and temperatures but makes those background conditions less favorable for eddy growth. For climates similar to the present day, the latter effect wins out, and moisture weakens midlatitude eddy activity. The model hierarchy includes a moist two-layer quasigeostrophic (QG) model and an idealized moist general circulation model (GCM). In the QG model, EKE increases when moisture is added to simulations with fixed baroclinicity, closely following a previously derived scaling. But in both models, moisture decreases EKE when environmental conditions are allowed to vary. We explain these results by examining the models’ mean available potential energy (MAPE) and by calculating terms in the models’ Lorenz energy cycles. In the QG model, the EKE decreases because precipitation preferentially forms on the poleward side of the jet, releasing latent heat where the model is relatively cold and decreasing the MAPE, hence the EKE. In the moist GCM, the MAPE primarily decreases because the midlatitude stability increases as the model is moistened, with reduced meridional temperature gradients playing a secondary role. Together, these results clarify moisture’s role in driving the midlatitude circulation and also highlight several drawbacks of QG models for studying moist processes in midlatitudes.

Significance Statement
Dry models of the atmosphere have played a central role in the study of large-scale atmospheric dynamics. But we know that moisture adds much complexity, associated with phase changes, its effect on atmospheric stability, and the release of latent heat during condensation. Here, we take an important step toward incorporating moisture into our understanding of midlatitude dynamics by reconciling two diverging lines of literature, which suggest that atmospheric moisture can either increase or decrease midlatitude eddy kinetic energy. We explain these opposing results by showing that moisture not only makes individual eddies more energetic but also makes the environment in which eddies form less favorable for eddy growth. For climates similar to the present day, the latter effect wins out such that moisture decreases atmospheric eddy kinetic energy. We demonstrate this point using several different idealized atmospheric models, which allow us to gradually add complexity and to smoothly vary between moist and dry climates. These results add fundamental understanding to how moisture affects midlatitude climates, including how its effects change in warmer and moisture climates, while also highlighting some drawbacks of the idealized atmospheric models.