bluuebunny/crossref_metadata_2025 huggingface dataset:
ACR–ARS Practice Parameter on Informed Consent Radiation Oncology
Authors: Hurwitz Mark D. , Chundury Anupama , Goodman Chelain R. , Jones Joshua , Lo Simon S. , Saeed Hina , Small William , Schechter Naomi R.
Published: March 2023

Objectives:

Consent is a communication process between the patient and a health care provider, in which both parties have the opportunity to ask questions and exchange information relevant to the patient’s diagnosis and treatment. The process of informed consent is designed to protect a patient’s autonomy in their medical decision-making in the context of an asymmetric relationship with the health care system. A proper consent process assures a patient’s individual autonomy, reduces the opportunity for abusive conduct or conflicts of interest, and raises trust levels among participants. This document was developed as an educational tool to facilitate these goals.

Methods:

This practice parameter was produced according to the process described under the heading “The Process for Developing ACR Practice Parameters and Technical Standards” on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters—Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Committee members were charged with reviewing the prior version of the informed consent practice parameter published in 2017 and recommending additions, modifications, or deletions. The committee met through remote access and subsequently through an online exchange to facilitate the development of the revised document. Focus was given on identifying new considerations and challenges with informed consent given the evolution of the practice of radiation oncology in part driven by the COVID-19 pandemic and other external factors.

Results:

A review of the practice parameter published in 2017 confirmed the ongoing relevance of recommendations made at that time. In addition, the evolution of the practice of radiation oncology since the publication of the prior document resulted in the need for new topics to be addressed. These topics include remote consent either through telehealth or telephone and with the patient or their health care proxy.

Conclusions:

Informed consent is an essential process in the care of radiation oncology patients. This practice parameter serves as an educational tool designed to assist practitioners in optimizing this process for the benefit of all involved parties.
A Novel Approach to Calcium Destruction in Coronary and Peripheral Blood Vessels: Intravascular Lithotripsy
Authors: Lenchur Peter D. , Frishman William H.
Published: March 2023

Lithotripsy has been used for decades in the treatment of kidney stones and gallstones, in which ultrasound shock waves generated outside of the body are used to physically break up hardened masses. In the past decade, intravascular lithotripsy (IVL), a technology developed by Shockwave Medical Inc. (Santa Clara, CA), has emerged as a novel therapy for the treatment of vascular calcification. In the coronary blood vessels, IVL modifies arterial calcium and enables percutaneous coronary interventions to be performed in a safe and consistent manner, and in the peripheral blood vessels, IVL can be used as a standalone therapy in the treatment of calcified plaque in patients with peripheral artery disease (PAD). Due to the success of the Disrupt CAD and Disrupt PAD clinical trials, IVL is now FDA-approved in the United States for use in both patients with coronary artery disease (CAD) and PAD. The widespread adoption of IVL for PAD is likely to mirror the swift uptake seen in CAD. Although questions remain regarding IVL’s high cost and performance compared directly to other technologies such as atherectomy, its ease of use, speed, and safety makes its future extremely promising for the treatment of complex, heavily calcified lesions in both peripheral and coronary vessels. Despite this, more studies are certainly needed to determine in what clinical scenarios IVL should be considered as opposed to atherectomy and if there are types of calcified lesions where IVL is best utilized (ie, concentric vs eccentric).
FDY-5301: An Innovative Approach to The Treatment of Revascularization Coronary Injury
Authors: Williams Lauren E. , Frishman William H.
Published: March 2023

After experiencing an acute ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) is a preferred method of restoring blood flow to the heart. While this reperfusion has long-term benefits, it can result in reperfusion injury in the short term, which involves the formation of reactive oxygen species (ROS) and neutrophil recruitment. FDY-5301 is a sodium iodide-based drug that acts as a catalyst in the conversion of hydrogen peroxide to water and oxygen. FDY-5301 is designed to be administered as an intravenous bolus following a STEMI, before reperfusion with PCI, to reduce the damage associated with reperfusion injury. Clinical trials have shown FDY-5301 administration to be safe, feasible, and fast-acting in its ability to increase plasma iodide concentration, and the results are favorable in demonstrating potential efficacy. FDY-5301 shows potential in its use to reduce the effects of reperfusion injury, and ongoing Phase 3 trials will allow for continued evaluation of its performance.
Apical or Septal Right Ventricular Location in Patients Receiving Defibrillation Leads: A Systematic Review and Meta-Analysis
Authors: Santos Helder , Figueiredo Margarida , Paula Sofia B. , Santos Mariana , Osório Paulo , Portugal Guilherme , Valente Bruno , Lousinha Ana , Silva Cunha Pedro , Oliveira Mário
Published: March 2023

This study reviews the published data comparing the efficacy and safety of apical and septal right ventricle defibrillator lead positioning at 1-year follow-up. Systemic research on Medline (PubMed), ClinicalTrials.gov, and Embase was performed using the keywords “septal defibrillation,” “apical defibrillation,” “site defibrillation,” and “defibrillation lead placement,” including implantable cardioverter-defibrillator and cardiac resynchronization therapy devices. Comparisons between apical and septal position were performed regarding R-wave amplitude, pacing threshold at a pulse width of 0.5 ms, pacing and shock lead impedance, suboptimal lead performance, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, readmissions due to heart failure and mortality rates. A total of 5 studies comprising 1438 patients were included in the analysis. Mean age was 64.5 years, 76.9% were male, with a median LVEF of 27.8%, ischemic etiology in 51.1%, and a mean follow-up period of 26.5 months. The apical lead placement was performed in 743 patients and septal lead placement in 690 patients. Comparing the 2 placement sites, no significant differences were found regarding R-wave amplitude, lead impedance, suboptimal lead performance, LVEF, left ventricular end-diastolic diameter, and mortality rate at 1-year follow-up. Pacing threshold values favored septal defibrillator lead placement (P = 0.003), as well as shock impedance (P = 0.009) and readmissions due to heart failure (P = 0.02). Among patients receiving a defibrillator lead, only pacing threshold, shock lead impedance, and readmission due to heart failure showed results favoring septal lead placement. Therefore, generally, the right ventricle lead placement does not appear to be of major importance.
Updates on the Global Prevalence and Etiology of Constrictive Pericarditis: A Systematic Review
Authors: Kosmopoulos Marinos , Liatsou Εfstathia , Theochari Christina , Stavropoulos Amalia , Chatzopoulou Despoina , Mylonas Konstantinos S. , Georgiopoulos Georgios , Schizas Dimitrios
Published: March 2023

Constrictive pericarditis is a rare disease with poorly understood epidemiology. A systematic literature search was adopted to assess the region- and period-specific traits of constrictive pericarditis through Pubmed, EMBASE, and Scopus. Case reports and studies including less than 20 patients were excluded. The risk of bias was assessed through the Study Quality Assessment Tools developed by the National Heart Lung Blood Institute by 4 reviewers. Patient demographics, disease etiology, and mortality were the primary assessed outcomes. One hundred thirty studies with 11,325 patients have been included in this systematic review and meta-analysis. The age at diagnosis of constrictive pericarditis has markedly increased after 1990. Patients from Africa and Asia are considerably younger compared with those from Europe and North America. Moreover, there are differences in etiology, as tuberculosis remains the dominant cause of constrictive pericarditis in Africa and Asia but has been surpassed by history of previous chest surgery in North America and Europe. The human immunodeficiency virus affects 29.1% of patients from Africa diagnosed with constrictive pericarditis, a feature that is not observed on any other continent. The early mortality rate after hospitalization has improved. The variances of age at diagnosis and etiology of constrictive pericarditis should be considered by the clinician during the work-up of cardiac and pericardial diseases. An underlying human immunodeficiency virus infection complicates a significant portion of constrictive pericarditis cases in Africa. Early mortality has improved across the world but remains high.
Predictive value of liver fibrosis scores in cardiovascular diseases among hypertensive population
Authors: Xiong Shengjun , Yin Shizhang , Deng Wanshu , Zhao Yuanhui , Li Wenhang , Wang Pengbo , Li Zhao , Yang Hongmei , Zhou Ying , Yu Shasha , Guo Xiaofan , Sun Yingxian
Published: March 2023

Purpose:

To explore the predictive value of liver fibrosis scores [fibrosis-4, AST/platelet ratio index, BAAT score (BMI Age ALT TG), and BARD score (BMI AST/ALT Ratio Diabetes)] for the risk of cardiovascular disease (CVD) in a hypertensive population.

Methods:

A total of 4164 hypertensive participants without history of CVD were enrolled in the follow-up. Four liver fibrosis scores (LFSs) were used, including the fibrosis-4 (FIB-4), APRI, BAAT score, and BARD score. The endpoint was CVD incidence which was defined as stroke or coronary heart disease (CHD) during the follow-up period. Cox regression analyses were used to calculate hazard ratios between LFSs and CVD. Kaplan–Meier curve was used to show the probability of CVD in different levels of LFSs. Restricted cubic spline further explored whether the relationship between LFSs and CVD was linear. Finally, we assessed the discriminatory ability of each LFS for CVD was assessed using C-statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI).

Results:

During a median follow-up time of 4.66 years, 282 hypertensive participants had CVD. Kaplan–Meier curve showed that four LFSs were associated with CVD and high levels of LFSs significantly increase the probability of CVD in hypertensive population. In the multivariate Cox regression analysis, the adjusted hazard ratios for four LFSs were 3.13 in FIB-4, 1.66 in APRI, 1.47 in BAAT score, and 1.36 in BARD score. Moreover, after adding LFSs to original risk prediction model, we find that all four new models have higher C-statistics of CVD than the traditional model. Furthermore, the results of both NRI and IDI were positive, indicating that LFSs enhanced the effect on the prediction of CVD.

Conclusions:

Our study showed that LFSs were associated with CVD in hypertensive populations in northeastern China. Furthermore, it suggested that LFSs could be a new tool for identifying patients at high risk of primary CVD in a hypertensive population.
Intersectionality of Systemic Disadvantage on Mortality and Care Following TBI
Authors: Starosta Amy J. , Mata-Greve Felicia , Humbert Andrew , Zheng Zihan , Prado Maria G. , Au Margaret A. , Mollis Brenda , Stephens Kari A. , Hoffman Jeanne M.
Published: March 2023

Background:

People of color (POC), especially those who also hold social identities associated with disadvantage (non–English-speaking, female, older, lower socioeconomic level), continue to be underserved in the health system, which can result in poorer care and worsened health outcomes. Most disparity research in traumatic brain injury (TBI) focuses on the impact of single factors, which misses the compounding effect of belonging to multiple historically marginalized groups.

Objective:

To examine the intersectional impact of multiple social identities vulnerable to systemic disadvantage following TBI on mortality, opioid usage during acute hospitalization, and discharge location.

Methods:

Retrospective observational design utilizing electronic health records merged with local trauma registry data. Patient groups were defined by race and ethnicity (POC or non-Hispanic White), age, sex, type of insurance, and primary language (English-speaking vs non–English-speaking). Latent class analysis (LCA) was performed to identify clusters of systemic disadvantage. Outcome measures were then assessed across latent classes and tested for differences.

Results:

Over an 8-year period, 10 809 admissions with TBI occurred (37% POC). LCA identified a 4-class model. Groups with more systemic disadvantage had higher rates of mortality. Classes with older populations had lower rates of opioid administration and were less likely to discharge to inpatient rehabilitation following acute care. Sensitivity analyses examining additional indicators of TBI severity demonstrated that the younger group with more systemic disadvantage had more severe TBI. Controlling for more indicators of TBI severity changed statistical significance in mortality for younger groups.

Conclusion:

Results demonstrate significant health inequities in the mortality and access to inpatient rehabilitation following TBI along with higher rates of severe injury in younger patients with more social disadvantages. While many inequities may be related to systemic racism, our findings suggested an additive, deleterious effect for patients who belonged to multiple historically disadvantaged groups. Further research is needed to understand the role of systemic disadvantage for individuals with TBI within the healthcare system.
The healing arts
Authors: Murphy Sean P.
Published: March 2023

Art asks of us some measure of curiosity and then rewards our curiosity with an affirmation of the desire to explore self, others, and the world. A psychiatric-mental health nurse practitioner describes his path into nursing and the nurse practitioner role, informed by and informing his art.
Nurse practitioners and the Fulbright Scholar Program: My experience in India
Authors: Roberts Lisa R.
Published: March 2023

The Fulbright Scholar Program offers numerous awards, presenting nurse practitioners with opportunities to interact with colleagues around the world. As increasing acceptance of the nurse practitioner role is gaining acceptance and being defined in various countries across the world, with expanding role definitions, this represents a trailblazing opportunity to influence global representation. The recent completion of a Fulbright award experience in India is provided as an exemplar of the Fulbright opportunity. Nurse practitioner program development and continuing education are key to enhancing patient care and access to care among patients who need it most. To be a part of the effort to prepare nurse practitioners everywhere expands the reach beyond that of an individual nurse practitioner. We can learn from each other, share strategies for implementation across settings, and together address barriers to practice.
Mechanical Power Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome
Authors: Percy Andrew G. , Mai Mark V. , Bhalla Anoopindar K. , Yehya Nadir
Published: March 2023

Objectives:

Mechanical power (MP) transferred from the ventilator to the lungs has been proposed as a summary variable that may impact mortality in children with acute respiratory distress syndrome (ARDS). To date, no study has shown an association between higher MP and mortality in children with ARDS.

Design:

Secondary analysis of a prospective observational study.

Setting:

Single-center, tertiary, academic PICU.

Patients:

Five hundred forty-six intubated children with ARDS enrolled between January 2013 and December 2019 receiving pressure-controlled ventilation.

Interventions:

None.

Measurements and Main Results:

Higher MP was associated with increased mortality (adjusted hazard ratio [HR] 1.34 per 1 sd increase, 95% CI 1.08–1.65; p = 0.007). When assessing the contribution of individual components of MP, only positive end-expiratory pressure (PEEP) was associated with mortality (HR 1.32; p = 0.007), whereas tidal volume, respiratory rate, and driving pressure (ΔP = [peak inspiratory pressure (PIP)–PEEP]) were not. Finally, we tested whether there remained an association when specific terms were removed from the MP equation by calculating MP from static strain (remove ΔP), MP from dynamic strain (remove PEEP), and mechanical energy (remove respiratory rate). MP from static strain (HR 1.44; p < 0.001), MP from dynamic strain (HR 1.25; p = 0.042), and mechanical energy (HR 1.29; p = 0.009) were all associated with mortality. MP was associated with ventilator-free days only when using MP normalized to predicted body weight, but not when using measured weight.

Conclusions:

Higher MP was associated with mortality in pediatric ARDS, and PEEP appears to be the component most consistently driving this association. As higher PEEP is used in sicker patients, the association between MP and mortality may reflect a marker of illness severity rather than MP itself being causal for mortality. However, our results support future trials testing different levels of PEEP in children with ARDS as a potential means to improve outcome.
Long-Term Outcomes After External Maxillary Distraction Surgery in Patients With Down Syndrome
Authors: Arnold Sydney H. , Figueroa Alvaro A. , Wiegmann Aaron L. , Lee Jugyeong , Padala Soumya , Hamati Fadi , Hansdorfer Marek A. , Tragos Christina
Published: March 2023

Background:

Patients with Down syndrome have severe facial deformities that can precipitate functional consequences and social stigmatization. Craniofacial surgical intervention can play a role in improving these symptoms and patient quality of life. The objective of this study was to investigate the long-term outcomes of distraction osteogenesis and orthognathic surgical intervention in patients with Down syndrome.

Materials and Methods:

Charts of 3 patients with Down syndrome who were treated with external maxillary distraction osteogenesis were retrospectively reviewed. The patients’ caregivers were prospectively interviewed between 10 and 15 years after surgery to determine surgical stability, long-term function, and quality of life status.

Results:

All patients and their caregivers reported excellent results with improvements in function and quality of life. Facial skeletal changes have been stable over time. The cephalometric analysis demonstrated significant maxillary advancement in all 3 patients and mandibular changes to correct mandibular prognathism and asymmetry in the patient who underwent finishing orthognathic surgery.

Conclusions:

External maxillary distraction osteogenesis and orthognathic surgery may be considered in select patients with Down syndrome as part of their multidisciplinary health care. These interventions can result in long-term improvements in patient function and quality of life.
Interactions between insect vectors and plant pathogens span the parasitism–mutualism continuum
Authors: Santiago Ma. Francesca M. , King Kayla C. , Drew Georgia C.
Published: March 2023

Agricultural crops infected with vector-borne pathogens can suffer severe negative consequences, but the extent to which phytopathogens affect the fitness of their vector hosts remains unclear. Evolutionary theory predicts that selection on vector-borne pathogens will favour low virulence or mutualistic phenotypes in the vector, traits facilitating effective transmission between plant hosts. Here, we use a multivariate meta-analytic approach on 115 effect sizes across 34 unique plant–vector–pathogen systems to quantify the overall effect of phytopathogens on vector host fitness. In support of theoretical models, we report that phytopathogens overall have a neutral fitness effect on vector hosts. However, the range of fitness outcomes is diverse and span the parasitism–mutualism continuum. We found no evidence that various transmission strategies, or direct effects and indirect (plant-mediated) effects, of phytopathogens have divergent fitness outcomes for the vector. Our finding emphasizes diversity in tripartite interactions and the necessity for pathosystem-specific approaches to vector control.
Mechanical analogue for cities
Authors: Makris Nicos , Moghimi Gholamreza , Godat Eric , Vu Tue
Published: March 2023

Motivated from the increasing need to develop a science-based, predictive understanding of the dynamics and response of cities when subjected to natural hazards, in this paper, we apply concepts from statistical mechanics and microrheology to develop mechanical analogues for cities with predictive capabilities. We envision a city to be a matrix where cell-phone users are driven by the city’s economy and other incentives while using the collection of its infrastructure networks in a similar way that thermally driven Brownian particles are moving within a complex viscoelastic material. Mean-square displacements of thousands of cell-phone users are computed from GPS location data to establish the creep compliance and the resulting impulse response function of a city. The derivation of these time-response functions allows the synthesis of simple mechanical analogues that model satisfactorily the city’s behaviour under normal conditions. Our study concentrates on predicting the response of cities to acute shocks (natural hazards) that are approximated with a rectangular pulse; and we show that the derived solid-like mechanical networks predict that cities revert immediately to their pre-event response suggesting an inherent resilience. Our findings are in remarkable good agreement with the recorded response of the Dallas metroplex following the February 2021 North American winter storm.
Effect of defects and reinforcements on the mechanical behaviour of a bi-layered panel
Authors: Wu C. L. , Zhang L. L. , Yin H. M.
Published: March 2023

This paper investigates the mechanical behaviour of a bi-layered panel containing many particles in one layer and demonstrates the size effect of particles on the deflection. The inclusion-based boundary element method (iBEM) considers a fully bounded bi-material system. The fundamental solution for two-jointed half spaces has been used to acquire elastic fields resulting from source fields over inclusions and boundary-avoiding multi-domain integral along the interface. Eshelby’s equivalent inclusion method is used to simulate the material mismatch with a continuously distributed eigenstrain field over the equivalent inclusion. The eigenstrain is expanded at the centre of the inclusion, which provides tailorable accuracy based on the order of the polynomial of the eigenstrain. As a single-domain approach, the iBEM algorithm is particularly suitable for conducting virtual experiments of bi-layered composites with many defects or reinforcements for both local analysis and homogenization purposes. The maximum deflection of solar panel coupons is studied under uniform vertical loading merged with inhomogeneities of different material properties, dimensions and volume fractions. The size of defects or reinforcements plays a significant role in the deflection of the panel, even with the same volume fraction, as the substrate is relatively thin.
An EBV-associated atypical B cell signature in clinically isolated syndrome is implicated in progression of multiple sclerosis
Authors: SoRelle Elliott D. , Haukenfrers Ellora , Jain Vaibhav , Abramson Karen , Hocke Emily , Cooney Laura A. , Harris Kristina M. , Zamvil Scott S. , Gregory Simon G. , Luftig Micah A.
Published: March 2023

Expansion and pathogenicity of CD19+/CD20+/CD11c+/T-bet+atypical B cells (ABCs) are hallmarks of numerous autoimmune disorders and chronic infections. In many such cases Epstein-Barr virus (EBV) is another associated or etiologic factor, though EBV involvement in these diseases remains poorly understood. Notably, the expansion of pro-inflammatory ABCs and a putative causal role for EBV have been identified independently in multiple sclerosis (MS). A common precipitating event in MS onset is Clinically Isolated Syndrome (CIS), a neuroinflammatory demyelinating condition of which 60-80% of cases progress to relapsing-remitting MS (RRMS). Here we report single-cell gene and surface protein expression (scRNA/CITE-seq) in peripheral B cells collected longitudinally from patients with CIS during the Immune Tolerance Network STAyCIS Trial. We focus on the transcriptomic signatures of ABCs from this cohort, publicly available scRNA-seq datasets from six other autoimmune and chronic infectious diseases, andin vitroEBV infection. Conservation of an expanded ABC expression profile across diseases establishes ABC dysregulation as a feature of CIS. Critically, we also observed transcriptomic features that distinguished CIS andde novoEBV-infected ABCs from those found in healthy controls and other disease contexts. Outcome stratification of CIS samples revealed a rare yet distinctive pro-inflammatory ABC subset that was significantly underrepresented in long-term non-progressor (LTNP) versus cases with RRMS activity (∼5-fold difference). Collectively, this study provides evidence for altered ABC regulation – possibly arising from niche-specific responses to EBV infection – preceding MS onset.

Single-cell transcriptomics establishes an EBV-associated signature in T-bet+atypical B cells in CIS and a pro-inflammatory phenotype underrepresented in patients with no disease progression.
On the quest for novelty in ecology
Authors: Ottaviani Gianluigi , Martinez Alejandro , Petit Bon Matteo , Mammola Stefano
Published: March 2023

The volume of scientific publications continues to grow, making it increasingly challenging for scholars to publish papers that capture readers' attention. While making a truly significant discovery is one way to attract readership, another approach may involve tweaking the language to overemphasize the novelty of results. Using a dataset of 52,236 paper abstracts published between 1997 and 2017 in 17 ecological journals, we found that the relative frequency of novelty terms (e.g. groundbreaking, innovative) nearly doubled over time. All journals but one exhibited a positive trend in the use of novelty terms during the studied period. Conversely, we found no such trend for confirmatory terms (e.g. confirm, replicated). Importantly, only papers using novelty terms were associated with significantly higher citation counts and were more often published in journals with a higher impact factor. While increasing research opportunities are surely driving advances in ecology, the writing style of authors and the publishing habits of journals may better reflect the inherently confirmatory nature of ecological research. We call for an open discussion among researchers about the potential reasons and implications of this language-use and scientometrics issue.
Mechanistic modeling of social conditions into disease predictions for public health intervention-analyses: application to HIV
Authors: Gopalappa Chaitra , Khoshegbhal Amir
Published: March 2023

Background

As social and economic conditions are key determinants of HIV, the ‘National HIV/AIDS Strategy (NHAS)’, in addition to care and treatment metrics, aims to address mental health, unemployment, food insecurity, and housing instability, as a strategic plan for the Ending the HIV Epidemic initiative. Mechanistic models of HIV play a key role in identifying cost-effective intervention strategies, however, social conditions are typically not part of the modeling framework. HIV projections are typically simulated by modeling care and sexual behaviors, and transmissions as functions of those behaviors.

Methods

We developed a methodological framework, using Markov random field model to estimate joint probability distributions between social conditions and behaviors, to incorporate in a mechanistic model to simulate behaviors as functions of social conditions and HIV transmissions as a function of behaviors. As demonstration, we conducted two numerical applications in a national-level agent-based network model, Progression and Transmission of HIV (PATH 4.0). The first modeled care behavior (using viral suppression as proxy) as a function of depression, neighborhood, housing, poverty, education, insurance, and employment status. The second modeled sexual behaviors (number of partners and condom-use) as functions of employment, housing, poverty, and education status, using exchange sex as a mediator. Both simulated HIV transmissions and disease progression as functions of behaviors. We conducted what-if intervention analyses to estimate the impact of an ideal 100% efficacious intervention strategy.

Results

If we intervene on HIV infected persons with the social needs modeled here, such that their care behavior increases to become equal to that among persons who do not have those social needs, the overall viral suppression in persons with diagnosed HIV infection increases from 65.5% to 80% (79% to 83%), resulting in a 10-year cumulative national incidence reduction of 29% (20% to 41%). If we address the social needs modeled here among persons who exchange sex, such that their sexual behavior becomes equal to that among those who do not exchange sex, we can expect a 10-year cumulative national incidence reduction of 6% (2.5% to 14%).

Conclusions

We developed a methodological framework for modeling social conditions into intervention decision-analytic models, using the limited data to present two demonstrative applications. Routinely monitoring quantitative data on associations between social conditions and HIV risk behaviors, and efficacy of structural interventions can help develop a comprehensive mechanistic model to identify cost-effective intervention combinations and inform public health strategic plans.
Phenome-wide association study to explore the long-term symptoms after infection with novel coronavirus in the UK Biobank
Authors: Zhang Kai , Liu Xiaowen , Fu Ping , Zhao Yingqi , Yu Qingqing , Liu Shuling , Xue Fuzhong
Published: March 2023

Background

Observational research studies have shown that even after the acute phase, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect patients, and increase the risk of cardiovascular, mental, metabolic, and other disorders. However, the spectrum of diseases for individuals with a genetic predisposition to COVID-19 remains unclear.

Methods

We leveraged individual-level data from UK Biobank to implement a phenome-wide association study to explore the relationships between COVID-19 and 1061 diseases. Then, the inverse-variance weighted (IVW) method was adopted with summary-level data from global consortiums as sensitivity analyses combined with other MR methods with different model assumptions to identify robust associations.

Findings

The PheWAS found severe respiratory, hospitalized, and susceptibility COVID-19 had detrimental effects on 36, 37, and 51 kinds of diseases, separately. The IVW test found severe respiratory COVID-19 had detrimental effects on breast cancer [OR 95% CI: 1.065 (1.000-1.133)], pan-cancer [OR 95% CI: 1.002 (1.000-1.004)], and Alzheimer’s disease [OR 95% CI: 1.042 (1.005-1.081)], etc. Hospitalized COVID-19 had detrimental effects on ischemic stroke (IS) [OR 95%CI: 1.049 (1.001-1.100)], breast cancer [OR 95%CI: 1.139 (1.011-1.283)], and pan-cancer [OR 95%CI: 1.003 (1.000-1.006)], etc. Susceptibility COVID-19 had detrimental effects on deep vein thrombosis (DVT) of lower extremities [OR 95%CI: 2.392 (1.167-4.902)], venous thromboembolism [OR 95%CI: 1.962 (1.115-3.453)], pulmonary heart disease/diseases of pulmonary circulation [OR 95%CI: 1.767 (1.142-2.733)], IS (large artery atherosclerosis) [OR 95%CI: 1.405 (1.025-1.927)], myocardial infarction [OR 95%CI: 1.235 (1.012-1.509)], heart failure [OR 95%CI: 1.140 (1.009-1.287)], etc.

Interpretation

This study describes the extensive link between genetically determined COVID-19 and a broad range of diseases, especially those of the circulatory system, neuropsychiatric system, neoplasms, immune system, and digestive systems. Early detection and management of post-COVID-19 conditions could be tremendously beneficial to public health.

Funding

This work was supported by the National Natural Science Foundation of China (81773547 and 82173625) and the National Key Research and Development Program (2020YFC2003500).
Animal-vectored nutrient flows across resource gradients influence the nature of local and meta-ecosystem functioning
Authors: Rizzuto Matteo , Leroux Shawn J. , Schmitz Oswald J. , Wal Eric Vander , Wiersma Yolanda F. , Heckford Travis R.
Published: March 2023

Organisms moving across landscapes connect ecosystems in space and time, mediating nutrient, energy, and biomass exchanges. Meta-ecosystem ecology offers a framework to study how these flows affect ecosystem functions in space and time. However, meta-ecosystem models often represent consumer movement as diffusion along gradients of resources. Crucially, this assumes that consumer movement connects the same trophic compartments among patches of the same ecosystem. Yet, empirical evidence shows that organisms move across different ecosystems and connect diverse trophic compartments in diffusive and non-diffusive ways. Here, we derive a two-patch meta-ecosystem model that accounts for both types of organismal movement, and we investigate their influences on local and meta-ecosystem functions. We integrate two novel approaches in this classic meta-ecosystem model: a dispersers’ pool to capture the fraction of moving organisms and time scales separation to partition local and regional dynamics. We show that non-diffusive consumer movement increases landscape heterogeneity while diffusive consumer movement enhances source-sink dynamics. Local ecosystem differences driven by consumer movement type are less prevalent at meta-ecosystem extents. Thus, movement type is essential for predicting local ecosystem dynamics. Our results support recent calls to explicitly consider the role of consumers in shaping and maintaining ecosystem functions in space and time.
Polygenic regression uncovers trait-relevant cellular contexts through pathway activation transformation of single-cell RNA sequencing data
Authors: Ma Yunlong , Deng Chunyu , Zhou Yijun , Zhang Yaru , Qiu Fei , Jiang Dingping , Zheng Gongwei , Li Jingjing , Shuai Jianwei , Zhang Yan , Yang Jian , Su Jianzhong
Published: March 2023

Advances in single-cell RNA sequencing (scRNA-seq) techniques have accelerated functional interpretation of disease-associated variants discovered from genome-wide association studies (GWASs). However, identification of trait-relevant cell populations is often impeded by inherent technical noise and high sparsity in scRNA-seq data. Here, we developed scPagwas, a computational approach that uncovers trait-relevant cellular context by integrating pathway activation transformation of scRNA-seq data and GWAS summary statistics. scPagwas effectively prioritizes trait-relevant genes, which facilitates identification of trait-relevant cell types/populations with high accuracy in extensive simulated and real datasets. Cellular-level association results identified a novel subpopulation of naïve CD8+ T cells related to COVID-19 severity, and oligodendrocyte progenitor cell and microglia subsets with critical pathways by which genetic variants influence Alzheimer’s disease. Overall, our approach provides new insights for the discovery of trait-relevant cell types and improves the mechanistic understanding of disease variants from a pathway perspective.
Multi-omic dissection of ancestral heat stress memory responses inBrachypodium distachyon
Authors: Xinghai Zheng , Tan Qiao Wen , Lim Peng Ken , Mutwil Marek
Published: March 2023

Stressful environmental conditions, including heat stress (HS), are a major limiting factor in crop yield. Understanding the molecular mechanisms of plant stress memory and resilience is important for engineering more resistant plants and improving crop yield. To study how the different gene regulatory layers change upon repeated HS and how these layers are interconnected, we performed a dense temporal atlas of gene expression, alternative splicing, small and long noncoding RNAs, and DNA methylation inBrachypodium distachyon. Results show that a second HS induces changes in coding and noncoding RNA expression and alternative splicing and that DNA demethylation is responsible for mediating differential gene expression. We identified a long noncoding RNA regulatory network and provided evidence that lncRNAs positively regulate gene expression, while miRNAs are implicated in alternative splicing events. We reconstructed the ancestral heat memory network of flowering plants by comparing the dynamic responses ofArabidopsis thalianaandBrachypodium distachyon. These findings enhance our understanding of the complex inter-layer cross-talk governing HS resilience and memory and identify novel genes essential for these processes.
COVID-19 vaccination coverage and linkages with public willingness to receive vaccination prior to vaccine roll-out: Evidence from Rwanda
Authors: Ndishimye Pacifique , Martinez Gustavo S. , Hewins Benjamin , Ostadgavahi Ali Toloue , Kumar Anuj , Sharma Mansi , Karuhije Janvier , Nkeshimana Menelas , Nsanzimana Sabin , Kelvin David
Published: March 2023

The rapid development of multiple SARS-CoV-2 vaccines within one year of the virus’s emergence is unprecedented and redefines the timeline for vaccine approval and rollout. Consequently, over 13 billion COVID-19 vaccine doses have been administered worldwide, accounting for ∼70% of the global population. Despite this steadfast scientific achievement, many inequalities exist in vaccine distribution and procurement, particularly in low- and middle-income countries such as those in Africa. This stems from the cost of COVID-19 vaccines, storage and cold-chain challenges, distribution to remote areas, proper personnel training, and so on. In addition to logistical challenges, many developed nations rapidly procured available vaccines, administering second and third doses and leaving many developing nations without the first dose. In this paper, we explore the level of reception to COVID-19 vaccines prior to their availability in Rwanda using a survey-based approach. While several countries reported spikes in vaccine hesitancy generally coinciding with new information, new policies, or newly reported vaccine risks, Rwanda functions as an exemplar for controlling disease burden and educating locals regarding the benefits of vaccination. We show that, even before COVID-19 vaccines were available, many Rwandans (97%) recognized the importance of COVID-19 vaccination and (93%) were willing to receive a COVID-19 vaccine following vaccine availability. Our results underscore the level of preparedness in Rwanda, which rivals and outcompetes many developed nations in terms of vaccination rate (nearing 80% in Rwanda), vaccine acceptance, and local knowledge relating to vaccination. Furthermore, in addition to the whole-of-government coordination as well as tailored delivery approach, previously developed practices relating to vaccination and communication surrounding the Ebola Virus Disease may have compounded the COVID-19 vaccine program in Rwanda, prior to its implementation.
Divergent functional connectivity changes associated with white matter hyperintensities
Authors: Santillo Alexander F. , Strandberg Tor O. , Reislev Nina H. , Nilsson Markus , Stomrud Erik , Spotorno Nicola , van Westen Danielle , Hansson Oskar
Published: March 2023

Age-related white matter hyperintensities are a common feature and known to negatively impact structural integrity, functional connectivity and cognitive performance. However, this has yet to be fully understood mechanistically. We analysed multiple MRI modalities acquired in 465 non-demented individuals from the Swedish BioFINDER study including 334 cognitively normal and 131 participants with mild cognitive impairment. White matter hyperintensities were automatically quantified using fluid-attenuated inversion recovery MRI and parameters from diffusion tensor imaging were estimated in major white matter fibre tracts. We calculated fMRI resting state-derived functional connectivity within and between predefined cortical regions structurally linked by the white matter tracts and evaluated how change in functional connectivity is affected by white matter lesions and related to cognition, in the form of executive function and processing speed. We examined the functional changes using a measure of sample entropy. As expected hyperintensities were associated with disrupted structural white matter integrity and were linked to reduced functionalinterregionallobar connectivity, which related to decreased processing speed and executive function. Simultaneously, hyperintensities were also associated with increasedintraregionalfunctional connectivity, but only within the frontal lobe. This phenomenon was also associated with reduced cognitive performance. The increased connectivity was linked to increased entropy (reduced predictability and increased complexity) of the involved voxels’ blood oxygenation level dependent signal. Our findings expand our previous understanding of the impact of white matter hyperintensities on cognition by describing novel mechanisms that may be important beyond this particular type of brain lesions.
Mechanism of GTPase activation of a prokaryotic small Ras-like GTPase MglA by an asymmetrically interacting MglB dimer
Authors: Chakraborty Sukanya , Kanade Manil , Gayathri Pananghat
Published: March 2023

Cell polarity oscillations inMyxococcus xanthusmotility are driven by a prokaryotic small Ras-like GTPase, MglA, which switches from one cell pole to the other in response to extracellular signals. MglA dynamics is regulated by MglB, which functions both as a GAP (GTPase activating protein) and a GEF (guanine nucleotide exchange factor) for MglA. With an aim to dissect the role of asymmetry in the dual GAP and GEF activities of MglB, we generated a functional MglAB complex by co-expressing MglB with a linked construct of MglA and MglB. This strategy enabled us to generate mutations of individual MglB protomers (MglB1linked to MglA or MglB2) and delineate their role in GEF and GAP activities. We establish that the C-terminal helix of MglB1, but not MglB2, stimulates nucleotide exchange through a site away from the nucleotide-binding pocket, confirming an allosteric mechanism. Interaction between the N-terminal β-strand of MglB1and β0of MglA is essential for the GEF activity of MglB. Specific residues of MglB2which interact with Switch-I of MglA partially contribute to its GAP activity. Thus, the role of the MglB2protomer in the GAP activity of MglB is limited to restricting the conformation of MglA active site loops by steric hindrance. The direct demonstration of the allosteric mechanism of GEF action provides us new insights into the regulation of small Ras-like GTPases, a feature potentially present in many uncharacterized GEFs.
Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells
Authors: Gu Li , Zhu Yahui , Lee Maiya , Nguyen Albert , Ryujin Nicolas T , Huang Jian , Chamseddine Shadi , Xiao Lianchun , Mohamed Yehia I. , Kaseb Ahmed O. , Karin Michael , Shalapour Shabnam
Published: March 2023

Although viral hepatocellular carcinoma (HCC) is declining, non-viral HCC, which often is the end-stage of non-alcoholic or alcoholic steatohepatitis (NASH, ASH), is on an upward trajectory. Immune checkpoint inhibitors (ICI) that block the T cell inhibitory receptor PD-1 were approved for treatment of all HCC types. However, only a small portion of HCC patients show a robust and sustained response to PD-1 blockade, calling for improved understanding of factors that negatively impact response rate and duration and the discovery of new adjuvant treatments that enhance ICI responsiveness. Using a mouse model of NASH-driven HCC, we identified peritumoral fibrosis as a potential obstacle to T cell mediated tumor regression and postulated that anti-fibrotic medications may increase ICI responsiveness. We now show that the angiotensin II receptor inhibitor losartan, a commonly prescribed and safe antihypertensive drug, reduced liver and peritumoral fibrosis and substantially enhanced anti-PD-1 induced tumor regression. Although losartan did not potentiate T cell reinvigoration, it substantially enhanced HCC infiltration by effector CD8+T cells compared to PD-1 blockade alone. The beneficial effects of losartan correlated with inhibition of TGF-β receptor signaling, collagen deposition and depletion of immunosuppressive fibroblasts.

Significance

Immune checkpoint inhibitors are used in HCC treatment but overall response rates for single agent PD-1/PD-L1 blockers have remained stubbornly low. Using a mouse model of NASH-driven HCC, we show that co-treatment with the safe and inexpensive angiotensin II receptor inhibitor losartan substantially enhanced anti-PD-1 triggered HCC regression. Although losartan did not influence the reinvigoration of exhausted CD8+T cells it considerably enhanced their intratumoral invasion, which we postulated to be compromised by peritumoral fibrosis. Indeed, the beneficial effect of losartan correlated with inhibition of TGF-β signaling and collagen deposition, and depletion of immunosuppressive fibroblasts. Losartan should be evaluated for its adjuvant activity in HCC patients undergoing PD-1/PD-L1 blocking therapy.
The significant yet short-term influence of research covidization on journal citation metrics
Authors: Zheng Xiang , Ni Chaoqun
Published: March 2023

COVID-19 has emerged as a major research hotspot in recent years, leading to increased publications and citations of related papers. While concerns exist about the potential citation boost in journals publishing these papers, the specifics are not fully understood. This study uses a generalized difference-in-differences approach to examine the impact of publishing COVID-19 papers on journal citation metrics in the Health Sciences fields. Findings indicate that journals publishing COVID-19 papers in 2020 received significantly higher citation premiums due to COVID-19 in 2020 and continued to benefit from the premium in 2021 in certain fields. In contrast, journals that began publishing COVID-19 papers in 2021 experienced weaker citation premiums. Although the publication volume of non-COVID-19 papers also surged, these papers experienced insignificant or negative citation gains, even when published in the same journals as COVID-19 papers. COVID-19 papers published in high-impact journals brought more significant citation premiums to journals in most fields. These citation premiums can affect various citation-based journal metrics, such as our simulated impact factor, to different degrees. The results highlight a “gold rush” pattern in which early entrants establish their citation advantage in research hotspots and caution against using citation-based metrics for research assessment.