bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing the Effectiveness of Policy Measures to Avoid Next-Wave COVID-19 Infections and Deaths Using a Dynamic Simulation Model: Implications for Health Technology Assessment
Authors: Hagens Arnold , Cordova-Pozo Kathya , Postma Maarten , Wilschut Jan , Zino Lorenzo , van der Schans Jurjen 
Published: January 2022

ObjectiveThe goal of this study was to dynamically model next-wave scenarios to observe the impact of different lockdown measures on the infection rates (IR) and mortality for two different prototype countries, mimicking the 1st year of the COVID-19 pandemic in Europe.MethodsA dynamic simulation SIRD model was designed to assess the effectiveness of policy measures on four next-wave scenarios, each preceded by two different lockdowns. The four scenarios were (1) no-measures, (2) uniform measures, (3) differential measures based on isolating &gt; 60 years of age group, and (4) differential measures with additional contact reduction measures for the 20–60 years of age group. The dynamic simulation model was prepared for two prototype European countries, Northwestern (NW) and Southern (S) country. Both prototype countries were characterized based on age composition and contact matrix.ResultsThe results show that the outcomes of the next-wave scenarios depend on number of infections of previous lockdowns. All scenarios reduce the incremental deaths compared with a no-measures scenario. Differential measures show lower number of deaths despite an increase of infections. Additionally, prototype S shows overall more deaths compared with prototype NW due to a higher share of older citizens.ConclusionThis study shows that differential measures are a worthwhile option for controlling the COVID-19 epidemic. This may also be the case in situations where relevant parts of the population have taken up vaccination. Additionally, the effectiveness of interventions strongly depends on the number of previously infected individuals. The results of this study may be useful when planning and forecasting the impact of non-pharmacological interventions and vaccination campaigns.
Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes
Authors: Statsenko Yauhen , Habuza Tetiana , Smetanina Darya , Simiyu Gillian Lylian , Uzianbaeva Liaisan , Neidl-Van Gorkom Klaus , Zaki Nazar , Charykova Inna , Al Koteesh Jamal , Almansoori Taleb M. , Belghali Maroua , Ljubisavljevic Milos 
Published: January 2022

BackgroundThe human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one.ObjectiveTo work out a descriptive model of brain structural and functional changes in normal aging.Materials and MethodsBy using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U-test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T-test.ResultsWhite matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age.ConclusionThe article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results.
Unique Phenotypes With Corresponding Pathology in Late-Onset Hereditary Transthyretin Amyloidosis of A97S vs. V30M
Authors: Hsueh Hsueh-Wen , Chao Chi-Chao , Chang Koping , Jeng Yung-Ming , Katsuno Masahisa , Koike Haruki , Hsieh Sung-Tsang 
Published: January 2022

ObjectiveHereditary transthyretin amyloidosis (ATTRv) encompasses different phenotypes among various genotypes. The analysis of the natural history and risk factors of faster progression in different genotypes would refine the treatment strategy.MethodsThe clinical manifestations of ATTRv from A97S (p.A117S) of Taiwanese and late-onset V30M (p.V50M) of Japanese were compared. An autopsy study of A97S was performed.ResultsThere existed three unique features in the A97S cohort compared to the V30M cohort: (1) dysphagia, (2) carpal tunnel syndrome (CTS), and (3) onset age. First, dysphagia was common in A97S (53.4%) but not in V30M and served as a contributor to fast disease progression. All phases of swallowing were affected. In the autopsy pathology, there were extensive amyloid deposits in the viscera and nerves of the tongue, larynx, and esophagus. In A97S, 45 patients (43.3%) had a history of CTS before the onset of length-dependent symptoms by 3 years. The amyloid deposition was more prominent in the median nerve than that in the transverse carpal ligament. The onset age at different stages was younger in the A97S cohort than the V30M cohort by 4–5 years.ConclusionThese phenotypic characteristics together with autopsy pathology in A97S are distinct from V30M. Early dysphagia in A97S correlated with fast progression. In A97S, median neuropathy leading to CTS might be in a continuous spectrum of ATTRv course rather than an independent disease entity. Such observations may serve as a foundation to explore and analyze unique phenotypes among various genotypes.
Circadian Strain, Light Exposure, and Depressive Symptoms in Rural Communities of Southern Brazil
Authors: Pilz Luísa K. , Xavier Nicóli B. , Levandovski Rosa , Oliveira Melissa A. B. , Tonon André C. , Constantino Débora B. , Machado Valdomiro , Roenneberg Till , Hidalgo Maria Paz 
Published: January 2022

Irregular light–dark cycles and circadian/sleep disturbances have been suggested as risk or co-occurring factors in depression. Among a set of metrics developed to quantify strain on the circadian system, social jetlag (SJL) has been put forward as a measure of the discrepancy between biological and social clocks. Here, we approached the question on whether light exposure and SJL would also be associated with depressive symptoms in Quilombola communities in Southern Brazil. These rural communities are void of potential confounders of modern lifestyles and show low levels of SJL. 210 Quilombolas (age range 16–92; 56% women) were asked about their sleep times and light exposure using the Munich ChronoType Questionnaire (MCTQ). The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Additionally, we analyzed 7-day actimetry recordings in 124 subjects. BDI scores higher than 10 (having clinically significant depressive symptoms; controlled for age and sex in the multivariate analysis) were positively associated with SJL &gt;1 h and negatively associated with median light exposure during the day, especially in the morning from 8:00 to 10:00. Our results suggest that low light exposure during the day, and higher levels of SJL are associated with depressive symptoms; longitudinal and experimental studies are needed to understand the underlying mechanisms. Nevertheless, we highlight the potential of treatment strategies aimed at decreasing circadian strain and insufficient light exposure, which are suggested as areas of further research in Psychiatry.
Neurogenic Dysphagia in Subdural Hematoma
Authors: Won Sae-Yeon , Krieger Simon , Dubinski Daniel , Gessler Florian , Behmanesh Bedjan , Freiman Thomas M. , Konczalla Juergen , Seifert Volker , Lapa Sriramya 
Published: January 2022

IntroductionDysphagia is a common and severe symptom of traumatic brain injury (TBI) affecting up to 78% of patients. It is associated with pneumonia, increased morbidity, and mortality. Although subdural hematoma (SDH) accounts for over 50% of TBI, the occurrence of dysphagia in this subtype has not been investigated yet.MethodsAll patients with SDH admitted to the author's institution between the years 2007 and 2020 were included in the study. Patients with SDH and clinical suspicion for dysphagia received a clinical swallowing assessment by a speech and language pathologist (SLP). Furthermore, the severity of dysphagia was rated according to swallowing disorder scale. Functional outcome was evaluated by the Glasgow outcome scale (GOS).ResultsOut of 545 patients with SDH, 71 patients had dysphagia (13%). The prevalence of dysphagia was significantly lower in the surgical arm compared to the conservative arm (11.8 vs. 21.8%; OR 0.23; p = 0.02). Independent predictors for dysphagia were GCS &lt;13 at admission (OR 4.17; p &lt; 0.001), cardiovascular disease (OR 2.29; p = 0.002), and pneumonia (OR 2.88; p = 0.002), whereas the operation was a protective factor (OR 0.2; p &lt; 0.001). In a subgroup analysis, right-sided SDH was an additional predictor for dysphagia (OR 2.7; p &lt; 0.001). Overall, patients with dysphagia improved significantly under the SLP treatment from the initial diagnosis to hospital discharge (p &lt; 0.01). However, a subgroup of patients with the most severe grade of dysphagia showed no significant improvement. Patients with dysphagia had significantly worse outcomes (GOS 1–3) compared to those without dysphagia (48.8 vs. 26.4%; p &lt; 0.001).ConclusionDysphagia is a frequent symptom in SDH, and the early identification of dysphagia is crucial regarding the initiation of treatment and functional outcome. Surgery is effective in preventing dysphagia and should be considered in high-risked patients.
Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice
Authors: Huang Furong , Liu Xiujie , Xu Sheng , Hu Sitao , Wang Sisi , Shi Dibang , Wang Kaicheng , Wang Zhongxiang , Lin Qiongqiong , Li Shan , Zhao Siyuan , Jin KeKe , Wang Chuang , Chen Lei , Wang Fangyan 
Published: January 2022

BackgroundEstrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. Prevotella histicola (P. histicola), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of P. histicola and clarify its potential mechanisms.MethodsMice were treated with P. histicola and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&amp;E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.ResultsP. histicola significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, P. histicola significantly increases the abundance of intestinal flora, especially Lactobacillus and Akkermansia. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. P. histicola was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after P. histicola treatment.ConclusionOur data show that P. histicola significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. P. histicola may be therapeutically beneficial for PMD.
PET/CT Imaging of Activated Cancer-Associated Fibroblasts Predict Response to PD-1 Blockade in Gastric Cancer Patients
Authors: Rong Xiaoxiang , Lv Jinyu , Liu Yantan , Wang Zhaojun , Zeng Dongqiang , Li Yuedan , Li Shaowei , Wu Jianhua , Shen Zheyu , Shi Min , Liao Wangjun , Wu Zhenzhen , Wang Chunlin 
Published: January 2022

BackgroundPromising development in immune checkpoint blockade (ICB) therapy has shown remarkable results in the treatment of gastric cancer (GC). However, the objective response rate in GC remains unsatisfactory. Noninvasive imaging to predict responses to ICB therapy via tumor microenvironment (TME) assessment is needed. Accordingly, this study aimed to evaluate the role of 68Ga-FAPI-04 PET/CT in the assessment of the immunosuppressive TME in GC and to cross-correlate imaging findings with responses to ICB therapy.MethodsThe correlation between fibroblast-activation-protein (FAP) expression and immunosuppressive cell infiltration was analyzed using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and GC tissue microarrays. To characterize the TME, TMEscores were calculated based on RNA-seq data from four GC patients. A total of 21 patients with GC underwent 68Ga-FAPI-04 PET/CT before ICB treatment, and two of them were imaged after ICB therapy.ResultsFAP expression was found to be closely correlated with poor prognosis and infiltration of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), exhausted T cells, and regulatory T cells (Tregs) in GC. We also found a strong relationship (R2 = 0.9678, p = 0.0162) between 68Ga-FAPI-04 uptake and TMEscore. Further analyses indicated that high 68Ga-FAPI-04 uptake was correlated with reduced therapeutic benefits from ICB therapy.Conclusions68Ga-FAPI-04 PET/CT may be used to noninvasively image the cancer-associated fibroblasts immunosuppressive TME in vivo and also potentially serve as a predictive biomarker of survival and antitumor immune response among patients who received ICB therapies.
Low-Dose 68 Ga-PSMA Prostate PET/MRI Imaging Using Deep Learning Based on MRI Priors
Authors: Deng Fuquan , Li Xiaoyuan , Yang Fengjiao , Sun Hongwei , Yuan Jianmin , He Qiang , Xu Weifeng , Yang Yongfeng , Liang Dong , Liu Xin , Mok Greta S. P. , Zheng Hairong , Hu Zhanli 
Published: January 2022

Background68 Ga-prostate-specific membrane antigen (PSMA) PET/MRI has become an effective imaging method for prostate cancer. The purpose of this study was to use deep learning methods to perform low-dose image restoration on PSMA PET/MRI and to evaluate the effect of synthesis on the images and the medical diagnosis of patients at risk of prostate cancer.MethodsWe reviewed the 68 Ga-PSMA PET/MRI data of 41 patients. The low-dose PET (LDPET) images of these patients were restored to full-dose PET (FDPET) images through a deep learning method based on MRI priors. The synthesized images were evaluated according to quantitative scores from nuclear medicine doctors and multiple imaging indicators, such as peak-signal noise ratio (PSNR), structural similarity (SSIM), normalization mean square error (NMSE), and relative contrast-to-noise ratio (RCNR).ResultsThe clinical quantitative scores of the FDPET images synthesized from 25%- and 50%-dose images based on MRI priors were 3.84±0.36 and 4.03±0.17, respectively, which were higher than the scores of the target images. Correspondingly, the PSNR, SSIM, NMSE, and RCNR values of the FDPET images synthesized from 50%-dose PET images based on MRI priors were 39.88±3.83, 0.896±0.092, 0.012±0.007, and 0.996±0.080, respectively.ConclusionAccording to a combination of quantitative scores from nuclear medicine doctors and evaluations with multiple image indicators, the synthesis of FDPET images based on MRI priors using and 50%-dose PET images did not affect the clinical diagnosis of prostate cancer. Prostate cancer patients can undergo 68 Ga-PSMA prostate PET/MRI scans with radiation doses reduced by up to 50% through the use of deep learning methods to synthesize FDPET images.
Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases
Authors: Riva Natalia , Molina Manuel , Cornaló Berta L. , Salvador María V. , Savransky Andrea , Tenembaum Silvia , Katsicas María M. , Monteverde Marta , Cáceres Guido Paulo , Rousseau Marcela , Staciuk Raquel , González Correas Agustín , Zubizarreta Pedro , Imventarza Oscar , Lagomarsino Eduardo , Spitzer Eduardo , Tinelli Marcelo , Schaiquevich Paula 
Published: January 2022

Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (&lt;19 y.o.) received 187 infusions of rituximab Novex® (n = 155) or innovator rituximab (n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4–12.1, p&lt;0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1–0.8, and p&lt;0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02–5.4, and p &lt; 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2–0.9, and p &lt; 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001–1.0006, and p &lt; 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics.
An Evolutionary Algorithm to Personalize Stool-Based Colorectal Cancer Screening
Authors: van Duuren Luuk A. , Ozik Jonathan , Spliet Remy , Collier Nicholson T. , Lansdorp-Vogelaar Iris , Meester Reinier G. S. 
Published: January 2022

BackgroundFecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history.MethodsWe present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments.ResultsIn Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations.DiscussionThe method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice.
Assessment of Physiological Responses During Field Science Task Performance: Feasibility and Future Needs
Authors: Hill Jordan R. , Caldwell Barrett S. 
Published: January 2022

ObjectiveBy understanding the physiological demands of different types of tasks that will be performed during extravehicular activity (EVA) on Mars, human performance safety risks can be mitigated. In addition, such understanding can assist in planning EVAs with an appropriate balance of human health and safety with scientific mission return.BackgroundThis paper describes the results of a study of technical feasibility performed within a Mars human research analog, with participants conducting scientifically relevant planetary science sample analysis and return tasks in two distinct field locations.MethodsThe authors collected heart rate, respiration rate, and heart rate variability (HRV) data, using commercial off-the-shelf hardware and software from study participants as they performed field science tasks within a concept of operations for a Mars science return human expedition mission. These data were remotely monitored, shared in real time, and later analyzed to identify different responses to different tasks in order to determine if there were any predictable or consistent patterns among participants.ResultsIt was ultimately determined that, while differences exist between responses to tasks, they are highly subject to multiple sources of individual variability, dynamics of evolving field science tasks, and demands of a demanding physical environment. Further, distributional analyses of participants do not support parametric statistical analysis techniques.ConclusionThe authors conclude that the physiology of individual astronauts should be extensively studied and modeled to support individualized automated monitoring tools for each crew member that is sent to Mars. Application: Physiological monitoring for specialized populations will require significant individual-level analysis, baselining, and bootstrap statistical methods to enable appropriate human performance determinations.