bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism
Authors: Parksook Wasita W , Yozamp Nicholas , Hundemer Gregory L , Moussa Marwan , Underhill Jonathan , Fudim Tali , Sacks Barry , Vaidya Anand 
Published: December 2021

Abstract

Background
Normal-appearing adrenal glands on cross-sectional imaging may still be the source of aldosterone production in primary aldosteronism (PA).

Methods
We evaluated the prevalence of aldosterone production among morphologically normal-appearing adrenal glands and the impact of this phenomenon on interpretations of localization studies and treatment decisions. We performed a retrospective cohort study of PA patients with at least 1 normal adrenal gland and reanalyzed contemporary studies to assess interpretations of imaging and adrenal venous sampling (AVS) at the individual patient and adrenal levels.

Results
Among 243 patients, 43 (18%) had bilateral normal-appearing adrenals and 200 (82%) had a unilateral normal-appearing adrenal, for a total of 286 normal-appearing adrenal glands. 38% of these normal-appearing adrenal glands were a source of aldosteronism on AVS, resulting in discordance between imaging and AVS findings in 31% of patients. Most patients with lateralizing PA underwent curative unilateral treatment (80%); however, curative treatment was pursued in 92% of patients who had concordant imaging-AVS results but in only 38% who had discordant results (P &lt; 0.05). In young patients, imaging-AVS discordance was detected in 32% of those under 45 years and 21% of those under 35 years. Among 20 contemporary studies (including 4,904 patients and 6,934 normal-appearing adrenal glands), up to 64% of normal-appearing adrenals were a source of aldosteronism resulting in 31% of patients having discordant results.

Conclusions
Morphologically normal-appearing adrenal glands are commonly the source of aldosterone production in PA, even among young patients. The lack of awareness of this issue may result in inappropriate treatment recommendations.
The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer
Authors: Hanna Kirollos S , Larson Samantha , Nguyen Jenny , Boudreau Jenna , Bulin Jennifer , Rolf Mallory 
Published: December 2021

Abstract

Purpose
The treatment landscape of advanced bladder cancer continues to evolve with novel therapeutics approved in recent years and many in the pipeline. Here we review the role of the novel agents enfortumab vedotin and sacituzumab govitecan in treatment of advanced disease.

Summary
Patients with advanced bladder cancer often first receive platinum-based therapy, while immune checkpoint inhibitors offer a maintenance option following cytotoxic chemotherapy or a second-line option. Despite various first- and second-line options, patients with significant comorbidities and treatment-related adverse events will experience disease progression requiring alternative treatment. Enfortumab vedotin and sacituzumab govitecan are novel antibody-drug conjugates approved in patients with advanced bladder cancer following platinum-based and immune checkpoint inhibitor therapy. Following platinum-based therapy and immunotherapy in patients with advanced bladder cancer, enfortumab vedotin, targeting Nectin-4, improves overall survival while sacituzumab govitecan, targeting Trop-2, is associated with a 27% response rate. With these new approaches to disease management, however, it remains critical to understand safety, efficacy, and operational considerations to optimize outcomes.

Conclusion
When selecting an antibody-drug conjugate to treat patients with bladder cancer, it is important to note the adverse event profile of each agent to optimize outcomes and safety for patients.
Influencers of Immediate Postmastectomy Reconstruction: A National Cancer Database Analysis
Authors: Danko Dora , Liu Yuan , Geng Feifei , Gillespie Theresa W 
Published: December 2021

Abstract

Background
The literature examining decision-making related to treatment and reconstruction for women with breast cancer has established that patient, clinical, and facility factors all play a role.

Objectives
The aim of this study was to use the National Cancer Database to determine how patient, clinical, and facility factors influence: (1) the receipt of immediate breast reconstruction; and (2) the type of immediate breast reconstruction received (implant-based, autologous, or a combination).

Methods
A total of 638,772 female patients with breast cancers (Tis-T3, N0-N1, or M0) who between 2004 and 2017 received immediate reconstruction following mastectomy were identified in the National Cancer Database. Univariate and multivariate logistic regression models were applied to identify characteristics associated with immediate breast reconstruction and type of reconstruction.

Results
Immediate breast reconstruction was more frequently associated with patients of White race, younger age, with private insurance, with lesser comorbidities, who resided in zip codes with higher median incomes or higher rates of high-school graduation, in urban areas, with Tis to T2 disease, or with involvement of &lt;4 lymph nodes (all odds ratios [ORs] &gt; 1.1). Negative predictors of immediate breast reconstruction were insurance status with Medicaid, Medicare, other government insurance, and none or unknown insurance (all ORs &lt; 0.79). Implant-based reconstruction was associated with non-Black race, uninsured status, completion of higher education, undifferentiated disease, and stage T0 disease (all ORs &gt; 1.10).

Conclusions
These findings confirm some previous studies on what patient, clinical, and facility factors affect decision-making, but also raise new questions that relate to the impact of third-party payer on receipt and type of reconstruction postmastectomy for breast cancer.
Causal inference for semi-competing risks data
Authors: Nevo Daniel , Gorfine Malka 
Published: December 2021

Summary
The causal effects of Apolipoprotein E $\epsilon4$ allele (APOE) on late-onset Alzheimer’s disease (AD) and death are complicated to define because AD may occur under one intervention but not under the other, and because AD occurrence may affect age of death. In this article, this dual outcome scenario is studied using the semi-competing risks framework for time-to-event data. Two event times are of interest: a nonterminal event time (age at AD diagnosis), and a terminal event time (age at death). AD diagnosis time is observed only if it precedes death, which may occur before or after AD. We propose new estimands for capturing the causal effect of APOE on AD and death. Our proposal is based on a stratification of the population with respect to the order of the two events. We present a novel assumption utilizing the time-to-event nature of the data, which is more flexible than the often-invoked monotonicity assumption. We derive results on partial identifiability, suggest a sensitivity analysis approach, and give conditions under which full identification is possible. Finally, we present and implement nonparametric and semiparametric estimation methods under right-censored semi-competing risks data for studying the complex effect of APOE on AD and death.
iCAV: an integrative database of cancer-associated viruses
Authors: Liu Bo , Zhang Qingfeng , Wang Jingou , Cao Shumin , Zhou Zhiyuan , Liu Ze-Xian , Cheng Han 
Published: December 2021

AbstractTo date, various studies have found that the occurrence of cancer may be related to viral infections. Therefore, it is important to explore the relationship between viruses and diseases. The International Agency for Research on Cancer has defined six types of viruses as Class 1 human carcinogens, including Epstein–Barr virus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus, human herpesvirus 8 and human papillomavirus, while Merkel cell polyomavirus is classified as ‘probably carcinogenic to humans’ (Group 2A). Therefore, in-depth research on these viruses will help clarify their relationship with diseases, and substantial efforts have been made to sequence their genomes. However, there is no complete database documenting these cancer-associated viruses, and researchers are not able to easily access and retrieve the published genomes. In this study, we developed iCAV, a database that integrates the genomes of cancer-related viruses and the corresponding phenotypes. We collected a total of 18 649 genome sequences from seven human disease-related viruses, and each virus was further classified by the associated disease, sample and country. iCAV is a comprehensive resource of cancer-associated viruses that provides browse and download functions for viral genomes.Database URL: http://icav.omicsbio.info/
Artificial intelligence-based detection of aortic stenosis from chest radiographs
Authors: Ueda Daiju , Yamamoto Akira , Ehara Shoichi , Iwata Shinichi , Abo Koji , Walston Shannon L , Matsumoto Toshimasa , Shimazaki Akitoshi , Yoshiyama Minoru , Miki Yukio 
Published: December 2021

Abstract

Aims
We aimed to develop models to detect aortic stenosis (AS) from chest radiographs—one of the most basic imaging tests—with artificial intelligence.

Methods and results
We used 10 433 retrospectively collected digital chest radiographs from 5638 patients to train, validate, and test three deep learning models. Chest radiographs were collected from patients who had also undergone echocardiography at a single institution between July 2016 and May 2019. These were labelled from the corresponding echocardiography assessments as AS-positive or AS-negative. The radiographs were separated on a patient basis into training [8327 images from 4512 patients, mean age 65 ±  (standard deviation) 15 years], validation (1041 images from 563 patients, mean age 65 ± 14 years), and test (1065 images from 563 patients, mean age 65 ± 14 years) datasets. The soft voting-based ensemble of the three developed models had the best overall performance for predicting AS with an area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 0.83 (95% confidence interval 0.77–0.88), 0.78 (0.67–0.86), 0.71 (0.68–0.73), 0.71 (0.68–0.74), 0.18 (0.14–0.23), and 0.97 (0.96–0.98), respectively, in the validation dataset and 0.83 (0.78–0.88), 0.83 (0.74–0.90), 0.69 (0.66–0.72), 0.71 (0.68–0.73), 0.23 (0.19–0.28), and 0.97 (0.96–0.98), respectively, in the test dataset.

Conclusion
Deep learning models using chest radiographs have the potential to differentiate between radiographs of patients with and without AS.

Lay Summary
We created artificial intelligence (AI) models using deep learning to identify aortic stenosis (AS) from chest radiographs. Three AI models were developed and evaluated with 10 433 retrospectively collected radiographs and labelled from echocardiography reports. The ensemble AI model could detect AS in a test dataset with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval 0.78–0.88). Since chest radiography is a cost-effective and widely available imaging test, our model can provide an additive resource for the detection of AS.
Heterogeneous Dynasties and Long-Run Mobility*
Authors: Benhabib Jess , Bisin Alberto , Fernholz Ricardo T 
Published: December 2021

Abstract
Recent empirical work has demonstrated a positive correlation between grandparent-child wealth rank, even after controlling for parent-child wealth rank, and a positive correlation between dynastic wealth ranks across almost six hundred years. We show that a simple heterogeneous agents model with idiosyncratic wealth returns generates a realistic wealth distribution, but fails to capture these long-run patterns of wealth mobility. An auto-correlated returns specification of this model also fails to capture both short- and long-run mobility. However, an extension of the heterogeneous agents model that includes permanent heterogeneity in wealth returns is able to simultaneously match the wealth distribution and short- and long-run wealth mobility.
Genomic signatures and insights into host niche adaptation of the entomopathogenic fungus Metarhizium humberi
Authors: Iwanicki Natasha Sant′Anna , Botelho Ana Beatriz Riguetti Zanardo , Klingen Ingeborg , Júnior Italo Delalibera , Rossmann Simeon , Lysøe Erik 
Published: December 2021

Abstract
The genus Metarhizium is composed of species used in biological control programs of agricultural pests worldwide. This genus includes common fungal pathogen of many insects and mites and endophytes that can increase plant growth. Metarhizium humberi was recently described as a new species. This species is highly virulent against some insect pests and promotes growth in sugarcane, strawberry, and soybean crops. In this study, we sequenced the genome of M. humberi, isolate ESALQ1638, and performed a functional analysis to determine its genomic signatures and highlight the genes and biological processes associated with its lifestyle. The genome annotation predicted 10633 genes in M. humberi, of which 92.0% are assigned putative functions, and ∼17% of the genome was annotated as repetitive sequences. We found that 18.5% of the M. humberi genome is similar to experimentally validated proteins associated with pathogen–host interaction. Compared to the genomes of eight Metarhizium species, the M. humberi ESALQ1638 genome revealed some unique traits that stood out, e.g., more genes functionally annotated as polyketide synthases (PKSs), overrepresended GO-terms associated to transport of ions, organic and amino acid, a higher percentage of repetitive elements, and higher levels of RIP-induced point mutations. The M. humberi genome will serve as a resource for promoting studies on genome structure and evolution that can contribute to research on biological control and plant biostimulation. Thus, the genomic data supported the broad host range of this species within the generalist PARB clade and suggested that M. humberi ESALQ1638 might be particularly good at producing secondary metabolites and might be more efficient in transporting amino acids and organic compounds.
Ameliorating Effects of Lifelong Physical Activity on Healthy Aging and Mitochondrial Function in Human White Adipose Tissue
Authors: Gudiksen Anders , Qoqaj Albina , Ringholm Stine , Wojtaszewski Jørgen , Plomgaard Peter , Pilegaard Henriette 
Published: December 2021

AbstractGrowing old is patently among the most prominent risk factors for lifestyle-related diseases and deterioration in physical performance. Aging in particular affects mitochondrial homeostasis, and maintaining a well-functioning mitochondrial pool is imperative in order to avoid age-associated metabolic decline. White adipose tissue (WAT) is a key organ in energy balance, and impaired mitochondrial function in adipocytes has been associated with increased low-grade inflammation, altered metabolism, excessive reactive oxygen species (ROS) production, and an accelerated aging phenotype. Exercise training improves mitochondrial health but whether lifelong exercise training can sufficiently maintain WAT mitochondrial function is currently unknown. Therefore, to dissect the role and dose-dependence of lifelong exercise training on aging WAT metabolic parameters and mitochondrial function, young and older untrained, as well as moderately and highly exercise trained older male subjects were recruited and abdominal subcutaneous (s)WAT biopsies and venous blood samples were obtained to measure mitochondrial function and key metabolic factors in WAT and plasma. Mitochondrial intrinsic respiratory capacity was lower in sWAT from older than from young subjects. In spite of this, maximal mitochondrial respiration per wet weight, markers of oxidative capacity, and mitophagic capacity were higher in sWAT from the lifelong highly exercise trained group than all other groups. Furthermore, ROS emission was generally lower in sWAT from lifelong highly exercise trained subjects than older untrained subjects. Taken together, aging reduces intrinsic mitochondrial respiration in human sWAT, but lifelong high-volume exercise training increases oxidative capacity by increasing mitochondrial volume likely contributing to healthy aging.
Comparing Effects of FOXO3 and Residing in Urban Areas on Longevity: A Gene–Environment Interaction Study
Authors: Ji John S , Liu Linxin , Yan Lijing L , Zeng Yi 
Published: December 2021

Abstract
Forkhead box O3 (FOXO3) is a candidate longevity gene. Urban residents are also positively associated with longer life expectancy. We conducted a gene–environment interaction to assess the synergistic effect of FOXO3 and urban/rural environments on mortality. We included 3 085 older adults from the Chinese Longitudinal Healthy Longevity Survey. We used single-nucleotide polymorphisms (SNPs) rs2253310, rs2802292, and rs4946936 to identify the FOXO3 gene and classified residential locations as “urban” and “rural.” Given the open cohort design, we used the Cox-proportional hazard regression models to assess the mortality risk. We found the minor allele homozygotes of FOXO3 to have a protective effect on mortality (HR [95% CI] for rs4946936 TT vs CC: 0.807 [0.653–0.996]; rs2802292 GG vs TT: 0.812 [0.67–0.985]; rs2253310 CC vs GG: 0.808 [0.667–0.978]). Participants living in urban areas had a lower risk of mortality (HR of the urban vs the rural: 0.854 [0.759–0.962]). The interaction between FOXO3 and urban and rural regions was statistically significant (pinteraction &lt; .01). Higher air pollution (fine particulate matter: PM2.5) and lower residential greenness (Normalized Difference Vegetation Index [NDVI]) both contributed to higher mortality. After adjusting for NDVI and PM2.5, the protective effect size of FOXO3 SNPs was slightly attenuated while the protective effect size of living in an urban environment increased. The effect size of the beneficial effect of FOXO3 on mortality is roughly equivalent to that of living in urban areas. Our research findings indicate that the effect of places of residence and genetic predisposition of longevity are intertwined.
Self-Perceptions of Aging Moderate Associations of Within- and Between-Persons Perceived Stress and Physical Health Symptoms
Authors: Witzel Dakota D , Turner Shelbie G , Hooker Karen 
Published: December 2021

Abstract

Objectives
To examine how self-perceptions of aging (SPA) moderated within- and between-persons perceived stress associations with physical health symptoms.

Methods
A community-dwelling sample of 103 adults (Meanage = 63, range = 52–88) participated in an online microlongitudinal study for 100 days (Noccasions = 7,064). Participants completed baseline surveys consisting of SPA, social connections, and demographics followed by 100 daily surveys including information about daily stress perceptions and physical health. Utilizing generalized multilevel models, we examined whether daily fluctuations and average levels of perceived stress over 100 days affected physical health symptoms and whether these associations varied by SPA.

Results
Adults who had higher perceived stress, on average across 100 days, reported significantly more physical health symptoms compared to individuals with lower perceived stress on average (p &lt; .05). On days when individuals reported higher perceived stress than their own average, they had a higher likelihood of reporting more physical health symptoms compared to days when their perceived stress was lower than their own average (p &lt; .05). Further, SPA significantly moderated associations between both within- and between-persons perceived stress and physical health symptoms (ps &lt; .05). Individuals with more positive SPA were less affected by high levels of perceived stress—both on average and on days when perceived stress was higher than their own average.

Discussion
More positive SPA significantly dampened the impact of perceived stress, suggesting the importance of SPA as an individual characteristic within stress processes. Future work should examine how daily changes in SPA may exacerbate or mitigate the impacts of daily stress processes and health outcomes.
Health literacy as a social vaccine in the COVID-19 pandemic
Authors: Okan Orkan , Messer Melanie , Levin-Zamir Diane , Paakkari Leena , Sørensen Kristine 
Published: December 2021

Summary
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus in the coronavirus family, causing the coronavirus disease (COVID-19). Biomedical vaccines are key but alongside biomedical vaccines, a social vaccine can be similarly useful to prevent infection from SARS-CoV-2, if applied as a health promotion strategy. In order to slow down and control the spread of SARS-CoV-2, applying the social vaccine concept should be considered in parallel. From a health promotion perspective, a social vaccine is a process of social and political mobilization driven by governmental and non-governmental organizations aiming at populations by applying interventions such as health communication, education and mass media campaigns as well as determinant-based programs to address environmental factors influencing personal behavior and community capacities to cope with and overcome the societal burdens of COVID-19. In this context, health literacy is significant, as seen in the role it plays in empowering citizens during the COVID-19 pandemic and enabling them to deal with health information considering COVID-19. As a public health strategy, health literacy as a social vaccine will enable individuals and communities to mitigate the spread of the virus by understanding and applying information as provided through governments and health authorities. The aim of this article is to explore health literacy as a promising social vaccine and opportunity to utilize social vaccination and thus be considered as a key public health approach—both bottom-up and top-down—to support the combat of COVID-19 and future states of emergency.
Predictors of Plasmodium falciparum Infection in the First Trimester Among Nulliparous Women From Kenya, Zambia, and the Democratic Republic of the Congo
Authors: Leuba Sequoia I , Westreich Daniel , Bose Carl L , Powers Kimberly A , Olshan Andy , Taylor Steve M , Tshefu Antoinette , Lokangaka Adrien , Carlo Waldemar A , Chomba Elwyn , Liechty Edward A , Bucher Sherri L , Esamai Fabian , Jessani Saleem , Saleem Sarah , Goldenberg Robert L , Moore Janet , Nolen Tracy , Hemingway-Foday Jennifer , McClure Elizabeth M , Koso-Thomas Marion , Derman Richard J , Hoffman Matthew , Bauserman Melissa 
Published: December 2021

Abstract

Background
Malaria can have deleterious effects early in pregnancy, during placentation. However, malaria testing and treatment are rarely initiated until the second trimester, leaving pregnancies unprotected in the first trimester. To inform potential early intervention approaches, we sought to identify clinical and demographic predictors of first-trimester malaria.

Methods
We prospectively recruited women from sites in the Democratic Republic of the Congo (DRC), Kenya, and Zambia who participated in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial. Nulliparous women were tested for first-trimester Plasmodium falciparum infection by quantitative polymerase chain reaction. We evaluated predictors using descriptive statistics.

Results
First-trimester malaria prevalence among 1513 nulliparous pregnant women was 6.3% (95% confidence interval [CI], 3.7%–8.8%] in the Zambian site, 37.8% (95% CI, 34.2%–41.5%) in the Kenyan site, and 62.9% (95% CI, 58.6%–67.2%) in the DRC site. First-trimester malaria was associated with shorter height and younger age in Kenyan women in site-stratified analyses, and with lower educational attainment in analyses combining all 3 sites. No other predictors were identified.

Conclusions
First-trimester malaria prevalence varied by study site in sub-Saharan Africa. The absence of consistent predictors suggests that routine parasite screening in early pregnancy may be needed to mitigate first-trimester malaria in high-prevalence settings.