bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with timely COVID-19 vaccination in a population-based cohort of patients with cancer
Authors: Powis Melanie , Sutradhar Rinku , Patrikar Aditi , Cheung Matthew , Gong Inna , Vijenthira Abi , Hicks Lisa K , Wilton Drew , Krzyzanowska Monika K , Singh Simron
Published: November 2022

Background

In many jurisdictions, cancer patients were prioritized for COVID-19 vaccination because of increased risk of infection and death. To understand sociodemographic disparities that affected timely receipt of COVID-19 vaccination among cancer patients, we undertook a population-based study in Ontario, Canada.

Methods

Patients older than 18 years and diagnosed with cancer January 2010 to September 2020 were identified using administrative data; vaccination administration was captured between approval (December 2020) up to February 2022. Factors associated with time to vaccination were evaluated using multivariable Cox proportional hazards regression.

Results

The cohort consisted of 356 535 patients, the majority of whom had solid tumor cancers (85.9%) and were not on active treatment (74.1%); 86.8% had received at least 2 doses. The rate of vaccination was 25% lower in recent (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.72 to 0.76) and nonrecent immigrants (HR = 0.80, 95% CI = 0.79 to 0.81). A greater proportion of unvaccinated patients were from neighborhoods with a high concentration of new immigrants or self-reported members of racialized groups (26.0% vs 21.3%, standardized difference = 0.111, P < .001), residential instability (27.1% vs 23.0%, standardized difference = 0.094, P < .001), or material deprivation (22.1% vs 16.8%, standardized difference = 0.134, P < .001) and low socioeconomic status (20.9% vs 16.0%, standardized difference = 0.041, P < .001). The rate of vaccination was 20% lower in patients from neighborhoods with the lowest socioeconomic status (HR = 0.82, 95% CI = 0.81 to 0.84) and highest material deprivation (HR = 0.80, 95% CI = 0.78 to 0.81) relative to those in more advantaged neighborhoods.

Conclusions

Despite funding of vaccines and prioritization of high-risk populations, marginalized patients were less likely to be vaccinated. Differences are likely due to the interplay between systemic barriers to access and cultural or social influences affecting uptake.
Functional variation in the non-coding genome: molecular implications for food security
Authors: Gullotta Giorgio , Korte Arthur , Marquardt Sebastian
Published: November 2022

The growing world population, in combination with the anticipated effects of climate change, is pressuring food security. Plants display an impressive arsenal of cellular mechanisms conferring resilience to adverse environmental conditions, and humans rely on these mechanisms for stable food production. The elucidation of the molecular basis of the mechanisms used by plants to achieve resilience promises knowledge-based approaches to enhance food security. DNA sequence polymorphisms can reveal genomic regions that are linked to beneficial traits of plants. However, our ability to interpret how a given DNA sequence polymorphism confers a fitness advantage at the molecular level often remains poor. A key factor is that these polymorphisms largely localize to the enigmatic non-coding genome. Here, we review the functional impact of sequence variations in the non-coding genome on plant biology in the context of crop breeding and agricultural traits. We focus on examples of non-coding with particularly convincing functional support. Our survey combines findings that are consistent with the view that the non-coding genome contributes to cellular mechanisms assisting many plant traits. Understanding how DNA sequence polymorphisms in the non-coding genome shape plant traits at the molecular level offers a largely unexplored reservoir of solutions to address future challenges in plant growth and resilience.
Spread of Sporothrix spp. through respiratory droplets from infected cats: A potential route of transmission
Authors: de Andrade Galliano Daros Bastos Fernanda , Raimundo Cognialli Regielly Caroline , Rodrigues de Farias Marconi , dos Santos Monti Fabiana , Wu Karen , Queiroz-Telles Flávio
Published: November 2022

Cases of cat-transmitted sporotrichosis in Brazil have increased in recent years. We collected respiratory secretions expelled while sneezing from 28 cats diagnosed with sporotrichosis. We identified the presence of Sporothrix spp. in respiratory droplets expelled in the sneeze of infected cats. The results raise concerns about a new transmission route for cat-transmitted sporotrichosis. Physicians who diagnose and treat human cases of sporotrichosis should be aware of this potential new transmission method to improve clinical suspicion. Approximately half of patients with granulomatous conjunctival sporotrichosis did not report experiencing traumatic injury from cats.
Adaptive optics and VLBA imaging observations of recoiling supermassive black hole candidates
Authors: Kim D-C , Kim Minjin , Yoon Ilsang , Momjian E , Kim Ji Hoon , Letai J , Evans A S
Published: November 2022

We present the results of high-resolution adaptive optics imaging observations of four kinematically identified recoiling supermassive black hole (rSMBH) candidates. Ellipse fitting was carried out to measure the spatial offset between the active galactic nucleus (AGN) and the centre of the host galaxy. Two rSMBH candidates (J1713 + 3523 and J2054 + 0049) are found to be offset AGN. However, the Very Long Baseline Array 1.5 GHz continuum imaging observation and spectral decomposition of the [O iii]5007 line suggest that J1713 + 3523 is a dual AGN and its spatial offset is not due to a recoil event. The spatial offset between the AGN and the centre of the host galaxy in J2054 + 0049 is 0.06 ± 0.01 arcsec (201 ± 22 pc). Spectral decomposition of J2054 + 0049 also suggests that it could be a dual AGN system and the measured spatial offset may not be due to a recoil event.
Absorption lines from magnetically driven winds in X-ray binaries – II. High resolution observational signatures expected from future X-ray observatories
Authors: Chakravorty Susmita , Petrucci Pierre-Olivier , Datta Sudeb Ranjan , Ferreira Jonathan , Wilms Joern , Jacquemin-Ide Jonatan , Clavel Maica , Marcel Gregoire , Rodriguez Jerome , Malzac Julien , Belmont Renaud , Corbel Stephane , Coriat Mickael , Henri Gilles , Parra Maxime
Published: November 2022

In our self-similar, analytical, magnetohydrodynamic (MHD) accretion–ejection solution, the density at the base of the outflow is explicitly dependent on the disc accretion rate – a unique property of this class of solutions. We had earlier found that the ejection index $p \gt \sim 0.1 (\dot{M}_{\rm{acc}} \propto r^p)$ is a key MHD parameter that decides if the flow can cause absorption lines in the high resolution X-ray spectra of black hole binaries. Here, we choose three dense warm solutions with p = 0.1, 0.3, 0.45 and carefully develop a methodology to generate spectra which are convolved with the Athena and XRISM response functions to predict what they will observe seeing through such MHD outflows. In this paper two other external parameters were varied – extent of the disc, $\rm {r_o|_{\rm{max}}} = 10^5, \, 10^6 \, \, \rm {r_G}$, and the angle of the line of sight, i ∼ 10–25°. Resultant absorption lines (H and He-like Fe, Ca, Ar) change in strength and their profiles manifest varying degrees of asymmetry. We checked if (a) the lines and (ii) the line asymmetries are detected, in our suit of synthetic Athena and XRISM spectra. Our analysis shows that Athena should detect the lines and their asymmetries for a standard 100 ks observation of a 100 mCrab source – lines with equivalent width as low as a few eV should be detected if the 6–8 keV counts are larger than 104–105 even for the least favourable simulated cases.
Chromosome maps of globular clusters from wide-field ground-based photometry
Authors: Jang S , Milone A P , Legnardi M V , Marino A F , Mastrobuono-Battisti A , Dondoglio E , Lagioia E P , Casagrande L , Carlos M , Mohandasan A , Cordoni G , Bortolan E , Lee Y-W
Published: November 2022

Hubble Space Telescope (HST) photometry is providing an extensive analysis of globular clusters (GCs). In particular, the pseudo-two-colour diagram dubbed 'chromosome map (ChM)’ allowed to detect and characterize their multiple populations with unprecedented detail. The main limitation of these studies is the small field of view of HST, which makes it challenging to investigate some important aspects of the multiple populations, such as their spatial distributions and the internal kinematics in the outermost cluster regions. To overcome this limitation, we analyse state-of-art wide-field photometry of 43 GCs obtained from ground-based facilities. We derived high-resolution reddening maps and corrected the photometry for differential reddening when needed. We use photometry in the U, B, and I bands to introduce the ΔcU, B, I versus ΔB, I ChM of red-giant branch (RGB) and asymptotic-giant branch stars. We demonstrate that this ChM, which is built with wide-band ground-based photometry, is an efficient tool to identify first- and second-generation stars (1G and 2G) over a wide field of view. To illustrate its potential, we derive the radial distribution of multiple populations in NGC 288 and infer their chemical composition. We present the ChMs of RGB stars in 29 GCs and detect a significant degree of variety. The fraction of 1G and 2G stars, the number of subpopulations, and the extension of the ChMs significantly change from one cluster to another. Moreover, the metal-poor and metal-rich stars of Type II GCs define distinct sequences in the ChM. We confirm the presence of extended 1G sequences.
Extending optical flare models to the UV: results from comparing of TESS and GALEX flare observations for M Dwarfs
Authors: Jackman James A G , Shkolnik Evgenya L , Million Chase , Fleming Scott , Richey-Yowell Tyler , Loyd R O Parke
Published: November 2022

The ultraviolet (UV) emission of stellar flares may have a pivotal role in the habitability of rocky exoplanets around low-mass stars. Previous studies have used white-light observations to calibrate empirical models which describe the optical and UV flare emission. However, the accuracy of the UV predictions of models has previously not been tested. We combined TESS optical and GALEX UV observations to test the UV predictions of empirical flare models calibrated using optical flare rates of M stars. We find that the canonical 9000-K black-body model used by flare studies underestimates the GALEX near-ultraviolet (NUV) energies of field age M stars by up to a factor of 6.5 ± 0.7 and the GALEX far-ultraviolet energies of fully convective field age M stars by 30.6 ± 10.0. We calculated energy correction factors that can be used to bring the UV predictions of flare models closer in line with observations. We calculated pseudo-continuum flare temperatures that describe both the white-light and GALEX NUV emission. We measured a temperature of 10 700 K for flares from fully convective M stars after accounting for the contribution from UV line emission. We also applied our correction factors to the results of previous studies of the role of flares in abiogenesis. Our results show that M stars do not need to be as active as previously thought in order to provide the NUV flux required for prebiotic chemistry, however, we note that flares will also provide more FUV flux than previously modelled.
Stellar age determination in the mass–luminosity plane
Authors: Higgins Erin R , Vink Jorick S
Published: November 2022

The ages of stars have historically relied on isochrone fitting of standardized grids of models. While these stellar models have provided key constraints on observational samples of massive stars, they inherit many systematic uncertainties, mainly in the internal mixing mechanisms applied throughout the grid, fundamentally undermining the isochrone method. In this work, we utilize the mass–lumiosity (M–L) plane of Higgins & Vink as a method of determining stellar age, with mixing-corrected models applying a calibrated core overshooting αov and rotation rate to fit the observational data. We provide multiple test-beds to showcase our new method, while also providing comparisons to the commonly used isochrone method, highlighting the dominant systematic errors. We reproduce the evolution of individual O stars, and analyse the wider sample of O and B supergiants from the VLT-FLAMES Tarantula Survey, providing dedicated models with estimates for αov, Ω/Ωcrit, and ultimately stellar ages. The M–L plane highlights a large discrepancy in the spectroscopic masses of the O supergiant sample. Furthermore the M–L plane also demonstrates that the evolutionary masses of the B supergiant sample are inappropriate. Finally, we utilize detached eclipsing binaries, VFTS 642 and VFTS 500, and present their ages resulting from their precise dynamical masses, offering an opportunity to constrain their interior mixing. For the near-TAMS system, VFTS 500, we find that both components require a large amount of core overshooting (αov ≃ 0.5), implying an extended main-sequence width. We hence infer that the vast majority of B supergiants are still burning hydrogen in their cores.
Multiwavelength periodicity search in a sample of γ-ray bright blazars
Authors: Otero-Santos J , Peñil P , Acosta-Pulido J A , Becerra González J , Raiteri C M , Carnerero M I , Villata M
Published: November 2022

We present the results of a long-term periodicity search in a sample of γ-ray blazars within a multiwavelength context. These blazars have been selected from the Steward Observatory sample as part of its optical monitoring program between 2008 and 2018. We study 15 sources with a temporal coverage in their optical total and polarized emission sufficiently large (>9 yr) to perform a reliable long-term periodicity analysis. We collect data from several observatories to extend the coverage, enabling the search of longer periods. In addition, data are also gathered in the high-energy (E > 100 MeV) γ-ray band from the Fermi Large Area Telescope; and in the 15 GHz radio band from the Owens Valley Radio Observatory. We identify 5 promising candidates to host quasi-periodic emission, AO 0235+164, PKS 1222+216, Mrk 501, BL Lacertae, and 1ES 2344+514 with periods in one or more bands and statistical significances ∼3σ after trial factor correction. AO 0235+164 shows a period of ∼8.2 yr in the R band; PKS 1222+216 has a quasi-periodic modulation in its total and polarized optical emission of ∼1.6 yr; Mrk 501 displays a ∼5 yr quasi-periodicity in optical and radio wavelengths; BL Lacertae presents a period of ∼1.8 yr in its polarized emission; and 1ES 2344 + 514 shows a hint of a ∼5.5 yr period in its optical R band. We interpret these results in the framework of the most common models and scenarios, namely the presence of a binary supermassive black hole system; or geometrical effects like helical or precessing jets.
Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty
Authors: Ogata Toru , Yamada Keiko , Miura Hiromasa , Hino Kazunori , Kutsuna Tatsuhiko , Watamori Kunihiko , Kinoshita Tomofumi , Ishibashi Yasuyuki , Yamamoto Yuji , Sasaki Tomoyuki , Matsuda Shuichi , Kuriyama Shinichi , Watanabe Mutsumi , Tomita Tetsuya , Tamaki Masashi , Ishibashi Teruya , Okazaki Ken , Mizu-uchi Hideki , Ishibashi Shojiro , Ma Yuan , Ito Yoichi M , Nakamura Kozo , Tanaka Sakae
Published: November 2022

Objectives

The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS.

Methods

A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively.

Results

After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60–74 years) and older (≥75 years) age groups.

Conclusions

We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.
HUSCH: an integrated single-cell transcriptome atlas for human tissue gene expression visualization and analyses
Authors: Shi Xiaoying , Yu Zhiguang , Ren Pengfei , Dong Xin , Ding Xuanxin , Song Jiaming , Zhang Jing , Li Taiwen , Wang Chenfei
Published: November 2022

Understanding gene expression patterns across different human cell types is crucial for investigating mechanisms of cell type differentiation, disease occurrence and progression. The recent development of single-cell RNA-seq (scRNA-seq) technologies significantly boosted the characterization of cell type heterogeneities in different human tissues. However, the huge number of datasets in the public domain also posed challenges in data integration and reuse. We present Human Universal Single Cell Hub (HUSCH, http://husch.comp-genomics.org), an atlas-scale curated database that integrates single-cell transcriptomic profiles of nearly 3 million cells from 185 high-quality human scRNA-seq datasets from 45 different tissues. All the data in HUSCH were uniformly processed and annotated with a standard workflow. In the single dataset module, HUSCH provides interactive gene expression visualization, differentially expressed genes, functional analyses, transcription regulators and cell–cell interaction analyses for each cell type cluster. Besides, HUSCH integrated different datasets in the single tissue module and performs data integration, batch correction, and cell type harmonization. This allows a comprehensive visualization and analysis of gene expression within each tissue based on single-cell datasets from multiple sources and platforms. HUSCH is a flexible and comprehensive data portal that enables searching, visualizing, analyzing, and downloading single-cell gene expression for the human tissue atlas.
ASCancer Atlas: a comprehensive knowledgebase of alternative splicing in human cancers
Authors: Wu Song , Huang Yue , Zhang Mochen , Gong Zheng , Wang Guoliang , Zheng Xinchang , Zong Wenting , Zhao Wei , Xing Peiqi , Li Rujiao , Liu Zhaoqi , Bao Yiming
Published: November 2022

Alternative splicing (AS) is a fundamental process that governs almost all aspects of cellular functions, and dysregulation in this process has been implicated in tumor initiation, progression and treatment resistance. With accumulating studies of carcinogenic mis-splicing in cancers, there is an urgent demand to integrate cancer-associated splicing changes to better understand their internal cross-talks and functional consequences from a global view. However, a resource of key functional AS events in human cancers is still lacking. To fill the gap, we developed ASCancer Atlas (https://ngdc.cncb.ac.cn/ascancer), a comprehensive knowledgebase of aberrant splicing in human cancers. Compared to extant databases, ASCancer Atlas features a high-confidence collection of 2006 cancer-associated splicing events experimentally proved to promote tumorigenesis, a systematic splicing regulatory network, and a suit of multi-scale online analysis tools. For each event, we manually curated the functional axis including upstream splicing regulators, splicing event annotations, downstream oncogenic effects, and possible therapeutic strategies. ASCancer Atlas also houses about 2 million computationally putative splicing events. Additionally, a user-friendly web interface was built to enable users to easily browse, search, visualize, analyze, and download all splicing events. Overall, ASCancer Atlas provides a unique resource to study the functional roles of splicing dysregulation in human cancers.
GenomicKB: a knowledge graph for the human genome
Authors: Feng Fan , Tang Feitong , Gao Yijia , Zhu Dongyu , Li Tianjun , Yang Shuyuan , Yao Yuan , Huang Yuanhao , Liu Jie
Published: November 2022

Genomic Knowledgebase (GenomicKB) is a graph database for researchers to explore and investigate human genome, epigenome, transcriptome, and 4D nucleome with simple and efficient queries. The database uses a knowledge graph to consolidate genomic datasets and annotations from over 30 consortia and portals, including 347 million genomic entities, 1.36 billion relations, and 3.9 billion entity and relation properties. GenomicKB is equipped with a web-based query system (https://gkb.dcmb.med.umich.edu/) which allows users to query the knowledge graph with customized graph patterns and specific constraints on entities and relations. Compared with traditional tabular-structured data stored in separate data portals, GenomicKB emphasizes the relations among genomic entities, intuitively connects isolated data matrices, and supports efficient queries for scientific discoveries. GenomicKB transforms complicated analysis among multiple genomic entities and relations into coding-free queries, and facilitates data-driven genomic discoveries in the future.
AsgeneDB: a curated orthology arsenic metabolism gene database and computational tool for metagenome annotation
Authors: Song Xinwei , Li Yiqun , Stirling Erinne , Zhao Kankan , Wang Binhao , Zhu Yongguan , Luo Yongming , Xu Jianming , Ma Bin
Published: November 2022

Arsenic (As) is the most ubiquitous toxic metalloid in nature. Microbe-mediated As metabolism plays an important role in global As biogeochemical processes, greatly changing its toxicity and bioavailability. While metagenomic sequencing may advance our understanding of the As metabolism capacity of microbial communities in different environments, accurate metagenomic profiling of As metabolism remains challenging due to low coverage and inaccurate definitions of As metabolism gene families in public orthology databases. Here we developed a manually curated As metabolism gene database (AsgeneDB) comprising 400 242 representative sequences from 59 As metabolism gene families, which are affiliated with 1653 microbial genera from 46 phyla. AsgeneDB achieved 100% annotation sensitivity and 99.96% annotation accuracy for an artificial gene dataset. We then applied AsgeneDB for functional and taxonomic profiling of As metabolism in metagenomes from various habitats (freshwater, hot spring, marine sediment and soil). The results showed that AsgeneDB substantially improved the mapping ratio of short reads in metagenomes from various environments. Compared with other databases, AsgeneDB provides more accurate, more comprehensive and faster analysis of As metabolic genes. In addition, we developed an R package, Asgene, to facilitate the analysis of metagenome sequencing data. Therefore, AsgeneDB and the associated Asgene package will greatly promote the study of As metabolism in microbial communities in various environments.
Clinical Trial Diversity in Oncology: FDA Takes Action with Post–Marketing Requirements or Commitments
Authors: Kim Janice , Kester Robert , Blumenthal Gideon
Published: November 2022

In recent years, there has been a renewed focus on promoting the inclusion of patients from racial and ethnic minority groups in oncology clinical trials. FDA Oncology has long pointed to the underrepresentation of racial minorities in registration trials leading to approval. US FDA’s Guidance on diversity discusses how diversity could be handled within clinical trials, giving recommendations on broadening eligibility criteria, inclusive trial practices, and alternative trial designs. While there is no specific guidance from the FDA on cancer clinical trials, the recommendation is to include a representative population applicable to the US population. With the recent renewed focus on diversity in oncology clinical trials, FDA Oncology has recently asked for the completion of a Diversity Plan during drug development and has issued post–marketing commitments and requirements at the time of approval. As FDA has started to issue post–marketing requirements or commitments regarding diversity in 2020, we sought to analyze the post–marketing studies asking for a study of racial and ethnic minorities issued by the FDA’s Office of Oncologic Diseases (OOD). The analysis demonstrated the need to increase the enrollment of a diverse patient population in cancer clinical trials.
The Late Roman Colonate
Authors: Lenski Noel
Published: November 2022

The ‘bound colonate’ is a subject of controversy among scholars, some of whom argue that it existed as a new status between free and slave, while others feel it was merely a fiscal concern that has been exaggerated into a historiographic myth. A survey of the evidence confirms that the bound colonate grew out of fiscal registration in the late third century but then took on a life of its own as a third status of semi-servility in the following century. It had become fully articulated by the early fifth century such that the many peasants enmeshed in it were compelled to live as permanent tenants bound to the land on which they were born and burdened with numerous impediments to their freedom. The bound colonate survived intact in the eastern empire through the sixth century but was modified in various forms in the post-Roman successor states of the West.
Slave Labour and Production
Authors: Rihll T.E.
Published: November 2022

This chapter examines the productive work that slaves performed in antiquity, and the lifestyles typically associated with different types of endeavour. Most slaves performed a variety of functions for their owners, from helping in the fields or the yard by day to keeping house, or bed, by night. Others were specialists in jobs like digging underground, or sailing in search of fish or markets, and had little or no contact with their masters on most days of their lives. Sophisticated systems were developed to motivate slaves to work hard under minimal supervision, creating an environment in which low-status workers made high-quality products, and through which strong partnerships could be formed despite the status distinction. Some roles offered slaves engaged in them opportunities to acquire wealth and freedom, whereas some were very dangerous or unpleasant. Slaves inevitably did the jobs that anyone who could refuse would not do.
Computational Modeling of Oddball Sequence Processing Exposes Common and Differential Auditory Network Changes in First-Episode Schizophrenia-Spectrum Disorders and Schizophrenia
Authors: Todd Juanita , Howard Zachary , Auksztulewicz Ryszard , Salisbury Dean
Published: November 2022

Background and Hypothesis

Differences in sound relevance filtering in schizophrenia are proposed to represent a key index of biological changes in brain function in the illness. This study featured a computational modeling approach to test the hypothesis that processing differences might already be evident in first-episode, becoming more pronounced in the established illness.

Study Design

Auditory event-related potentials to a typical oddball sequence (rare pitch deviations amongst regular sounds) were recorded from 90 persons with schizophrenia-spectrum disorders (40 first-episode schizophrenia-spectrum, 50 established illness) and age-matched healthy controls. The data were analyzed using dynamic causal modeling to identify the changes in effective connectivity that best explained group differences.

Study Results

Group differences were linked to intrinsic (within brain region) connectivity changes. In activity-dependent measures these were restricted to the left auditory cortex in first-episode schizophrenia-spectrum but were more widespread in the established illness. Modeling suggested that both established illness and first-episode schizophrenia-spectrum groups expressed significantly lower inhibition of inhibitory interneuron activity and altered gain on superficial pyramidal cells with the data indicative of differences in both putative N-methyl-d-aspartate glutamate receptor activity-dependent plasticity and classic neuromodulation.

Conclusions

The study provides further support for the notion that examining the ability to alter responsiveness to structured sound sequences in schizophrenia and first-episode schizophrenia-spectrum could be informative to uncovering the nature and progression of changes in brain function during the illness. Furthermore, modeling suggested that limited differences present at first-episode schizophrenia-spectrum may become more expansive with illness progression.
Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response
Authors: Ji Gong-Jun , Zalesky Andrew , Wang Yingru , He Kongliang , Wang Lu , Du Rongrong , Sun Jinmei , Bai Tongjian , Chen Xingui , Tian Yanghua , Zhu Chunyan , Wang Kai
Published: November 2022

Background and Hypothesis

Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS).

Study Design

The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient’s personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient’s atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map.

Results

The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients.

Conclusions

Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.
Advancing digital health equity: Directions for behavioral and social science research
Authors: Jaworski Beth K , Webb Hooper Monica , Aklin Will M , Jean-Francois Beda , Elwood William N , Belis Deshirée , Riley William T , Hunter Christine M
Published: November 2022

The field of digital health is evolving rapidly and encompasses a wide range of complex and changing technologies used to support individual and population health. The COVID-19 pandemic has augmented digital health expansion and significantly changed how digital health technologies are used. To ensure that these technologies do not create or exacerbate existing health disparities, a multi-pronged and comprehensive research approach is needed. In this commentary, we outline five recommendations for behavioral and social science researchers that are critical to promoting digital health equity. These recommendations include: (i) centering equity in research teams and theoretical approaches, (ii) focusing on issues of digital health literacy and engagement, (iii) using methods that elevate perspectives and needs of underserved populations, (iv) ensuring ethical approaches for collecting and using digital health data, and (v) developing strategies for integrating digital health tools within and across systems and settings. Taken together, these recommendations can help advance the science of digital health equity and justice.
Data-driven discovery of canonical large-scale brain dynamics
Authors: Piccinini Juan , Deco Gustavo , Kringelbach Morten , Laufs Helmut , Sanz Perl Yonatan , Tagliazucchi Enzo
Published: November 2022

Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observables derived from functional magnetic resonance recordings. The phase space analysis of the resulting equations revealed a predominance of stable spiral attractors, which optimized the similarity to the empirical data in terms of the synchronization, metastability, and functional connectivity dynamics. For stable limit cycles, departures from harmonic oscillations improved the fit in terms of functional connectivity dynamics. Eigenvalue analyses showed that proximity to a bifurcation improved the accuracy of the simulation for wakefulness, whereas deep sleep was associated with increased stability. Our results provide testable predictions that constrain the landscape of suitable biophysical models, while supporting noise-driven dynamics close to a bifurcation as a canonical mechanism underlying the complex fluctuations that characterize endogenous brain activity.
Genome-Wide Association to Study the Host-Specificity Determinants ofXanthomonas perforans
Authors: Newberry Eric A. , Minsavage Gerald V. , Holland Auston , Jones Jeffrey B. , Potnis Neha
Published: November 2022

Xanthomonas perforans and X. euvesicatoria are the causal agents of bacterial spot disease of tomato and pepper, endemic to the Southeastern United States. Although very closely related, the two bacterial species differ in host specificity, where X. perforans is the dominant pathogen of tomato and X. euvesicatoria that of pepper. This is in part due to the activity of avirulence proteins that are secreted by X. perforans strains and elicit effector-triggered immunity in pepper leaves, thereby restricting pathogen growth. In recent years, the emergence of several pepper-pathogenic X. perforans lineages has revealed variability within the bacterial species to multiply and cause disease in pepper, even in the absence of avirulence gene activity. Here, we investigated the basal evolutionary processes underlying the host range of this species using multiple genome-wide association analyses. Surprisingly, we identified two novel gene candidates that were significantly associated with pepper-pathogenic X. perforans and X. euvesicatoria. Both candidates were predicted to be involved in the transport/acquisition of nutrients common to the plant cell wall or apoplast and included a TonB-dependent receptor, which was disrupted through independent mutations within the X. perforans lineage. The other included a symporter of protons/glutamate, gltP, enriched with pepper-associated mutations near the promoter and start codon of the gene. Functional analysis of these candidates revealed that only the TonB-dependent receptor had a minor effect on the symptom development and growth of X. perforans in pepper leaves, indicating that pathogenicity to this host might have evolved independently within the bacterial species and is likely a complex, multigenic trait.
Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer
Authors: Mokhtech Meriem , Miccio Joseph A. , Johung Kimberly , Cecchini Michael , Stein Stacey , Narang Amol K. , Herman Joseph M. , Kunstman John , Haddock Michael G. , Anker Christopher J. , Jabbour Salma , Hallemeier Christopher L. , Jethwa Krishan R.
Published: November 2022

Background and Purpose:

Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC.

Methods:

Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P<0.05).

Results:

A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P<0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045).

Conclusions:

For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.
Radiographic Response of Solitary Plasmacytomas After Conformal Radiotherapy May Be Delayed
Authors: Kosydar Samuel , Gulhane Avanti , Libby Edward , Cowan Andrew J. , Kwok Mary , Lee Sarah S. , Green Damian J. , Coffey David , Holmberg Leona A. , Chen Delphine L. , Tseng Yolanda D.
Published: November 2022

Objective:

Although recurrence rates after radiotherapy for solitary plasmacytoma (SP) are well established, little is known about how SP responds radiographically, as most historical patients were treated in the 2D era. We evaluated the response to radiotherapy among SP patients staged and treated with 3D techniques, including proton therapy, which has not yet been previously reported.

Methods and Materials:

Between 2007 and 2021, 15 SP patients (4 extramedullary, 11 bone) staged with 3D imaging and bone marrow evaluation were consecutively treated with definitive radiotherapy. The best response was categorized in 9 evaluable patients according to response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST).

Results:

With a median follow-up of 34 months, 4 patients relapsed. The median time to the best response was ~2 years (26.6 mo RECIST, 25.4 mo PERCIST). Response rates differed based on response assessment criteria. PERCIST was associated with higher rates of complete (85.7%) or partial response (14.3%) compared with RECIST (16.7% complete, 33.3% partial). Two-year and 4-year PFS for extramedullary SP were 100% and 75%, compared with 91% and 55% for bone (P=0.75). Patients treated with proton therapy (n=5) did not appear to have different patterns of relapse (1 marginal, 1 distant) compared with those treated with photons or electrons (n=10; 2 distant).

Conclusions:

More conformal dose distribution with proton therapy does not appear to alter patterns of recurrence. Although response rates differ based on criteria by both RECIST and PERCIST assessments, the radiographic response may be slow and requires validation in other cohorts.
Changes in cardiovascular disease risk factors during menopausal transition in Japanese women: the Circulatory Risk in Communities Study (CIRCS)
Authors: Teramura Saki , Sankai Tomoko , Yamagishi Kazumasa , Umesawa Mitsumasa , Hayama-Terada Mina , Muraki Isao , Tanaka Mari , Kihara Tomomi , Ohira Tetsuya , Imano Hironori , Cui Renzhe , Shimizu Yuji , Okada Takeo , Kitamura Akihiko , Kiyama Masahiko , Iso Hiroyasu
Published: November 2022

Objective

We aimed to longitudinally clarify the changes in cardiovascular disease risk factors associated with menopause in Japanese women in the 2000s.

Methods

Of the 4,596 women who underwent health examinations between 2007 and 2012 in three communities of the Circulatory Risk in Communities Study, 263 women who reported going through menopause during that period were included in the study. We randomly selected 1,665 men as control subjects who participated in a health examination at least once between 2001 and 2009 and at least once between 2010 and 2018 by 1:1 pair-matching for age, community, and examination year. The health examination data from 3 to 6 years before (2001-2009) and after menopause age (2010-2018) were compared in terms of body mass index, systolic and diastolic blood pressure levels, serum total cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin A1c, hemoglobin, aspartate aminotransferase, alanine aminotransferase, and current smoker status.

Results

Compared with the men, the women showed a greater increase in serum total cholesterol (+16.7 vs −3.1 mg/dL, P < 0.001), non-high-density lipoprotein cholesterol (+15.9 vs −6.3 mg/dL, P < 0.001), fasting triglycerides (+1.2 vs +1.0 mg/dL, P = 0.027), triglycerides regardless of fasting status (+1.2 vs −0.9 mg/dL, P < 0.001), uric acid (+0.5 vs +0.2 mg/dL, P = 0.008), hemoglobin (+0.9 vs −0.3 g/dL, P < 0.001), aspartate aminotransferase (+2.9 vs −2.7 IU/L, P < 0.001), and alanine aminotransferase (+2.9 vs −2.6 IU/L, P < 0.001). No differences were found in the changes in body mass index, systolic and diastolic blood pressures, and hemoglobin A1c between the women and the matched men.

Conclusions

Menopause may be a crucial factor related to changes in serum total cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin, and liver enzymes.
Gender Differences in Anxiety, Depression, Insomnia, and Quality of Life in Heart Failure With Preserved Ejection Fraction: A Multicenter, Cross-sectional Study
Authors: Yang Xiaoyun , Wen Yi , Peng Huiji , Zhu Hongjin , Wang Wei Eric , Zhou Jianrong
Published: November 2022

Background

Patients with heart failure with preserved ejection fraction (HFpEF) are more often female, but gender differences in psychological distress in patients with HFpEF have not been determined.

Objective

We aimed to compare anxiety, depression, insomnia, and quality of life (QoL) between women and men with HFpEF.

Methods

A total of 263 consecutive hospitalized patients with HFpEF were enrolled in a multicenter study. Demographic and clinical characteristics were recorded. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), insomnia was assessed by the Insomnia Severity Index and Pittsburgh Sleep Quality Index, and QoL was assessed by the Kansas City Cardiomyopathy Questionnaire.

Results

Women accounted for 59% and men accounted for 41% of the patients with HFpEF. Women and men had similar New York Heart Association functional class and N-terminal pro–brain natriuretic peptide levels. Between women and men with HFpEF, similar depression prevalence (HADS-D: 4.9 ± 3.7 vs 4.1 ± 3.6, P = .222), insomnia severity (Insomnia Severity Index: 9.3 ± 6.4 vs 8.0 ± 6.5, P = .120), and QoL (Kansas City Cardiomyopathy Questionnaire: 46.6 ± 12.6 vs 47.6 ± 12.7, P = .738) were found when adjusting for potential confounders. Women had more severe anxiety (HADS-Anxiety: 2.4 ± 2.9 vs 1.6 ± 2.3, P = .025) and worse sleep quality (Pittsburgh Sleep Quality Index: 9.9 ± 4.6 vs 8.7 ± 4.5, P = .046) compared with men after adjustment.

Conclusions

There were no gender differences in depression, insomnia, and QoL in patients with HFpEF when adjusting for confounders. Women with HFpEF suffered more severe anxiety and sleep quality than men after adjustment. Thus, it is recommended that psychological distress in patients with HFpEF be assessed in clinical practice, and gender differences taken into consideration.
The role of noninvasive scoring systems for predicting cardiovascular disease risk in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Yi Mengshi , Peng Wei , Teng Fei , Kong Qingyan , Chen Zheyu
Published: November 2022

Backgrounds

Cardiovascular disease (CVD) is suggested as a leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). The aim of this work was to clarify the role of noninvasive scoring systems (NSSs) in predicting CVD risk among this population.

Methods

The PubMed, Web of Science, and Cochrane databases were searched until 23 March 2022. Meta-analysis was performed for three most commonly used NSS separately, that is, fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and AST/platelet ratio index (APRI).

Results

Totally, nine studies including 155 382 patients with NAFLD were enrolled. Patients with NAFLD had a higher risk of CVD with increasing FIB-4 score (1.94, 1.52–2.46), the association remained significant after adjustment for age, sex, body mass index, hypertension, and diabetes (2.44, 1.85–3.22). Similarly, a higher risk of CVD was also observed in patients with increasing NFS (2.17, 1.58–2.98) and APRI scores (1.36, 1.04–1.79) in the unadjusted model. However, in the adjusted model, the association was significant only for NFS (3.83, 1.40–10.43), but not for APRI (1.41, 0.79–2.51). Additionally, the increment in CVD risk was most noticeable in subgroup of FIB > 2.67 vs. FIB ≤ 1.3 (6.52, 3.07–13.86) and subgroup of NFS > 0.676 vs. NFS ≤ −1.455 (16.88, 5.68–50.23). All subgroup analyses showed significant associations between FIB-4, NFS, and risk of CVD. Sensitivity analyses did not modify these results.

Conclusions

FIB-4 and NFS might be useful in identifying those who are at higher risk of CVD among patients with NAFLD. However, APRI was not recommended for this use.