bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncological Outcomes for Patients Harboring Positive Surgical Margins Following Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective Multicentric Study on Behalf of the YAU Urothelial Group
Authors: Marcq Gautier , Afferi Luca , Neuzillet Yann , Nykopp Timo , Voskuilen Charlotte S. , Furrer Marc A. , Kassouf Wassim , Aziz Atiqullah , Bajeot Anne Sophie , Alvarez-Maestro Mario , Black Peter , Roupret Morgan , Noon Aidan P. , Seiler Roland , Hendricksen Kees , Roumiguie Mathieu , Pang Karl H. , Laine-Caroff Paul , Xylinas Evanguelos , Ploussard Guillaume , Moschini Marco , Sargos Paul
Published: November 2022

Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC. Methods: A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers. Patients receiving perioperative radiotherapy were excluded from the study. Kaplan–Meier curves were used to estimate patient survival. Cox regression analysis was used to identify predictors of survival. Results: Median age at surgery was 70 years (IQR 62–76) with 129 (33%) and 204 (52%) patients had pT3 and pT4 tumors, respectively. Nodal metastasis (pN+) was identified in 148 (38%). Soft tissue PSMs were found in 283 (72%) patients, urethral PSMs in 65 (16.5%), and ureteral PSMs were found in 73 (18.5%). The median follow-up time was 44 months (95% CI 32–60). Median LRFS, MRFS, RFS, CSS, and OS were 14 (95% CI 11–17), 12 (95% CI 10–16), 10 (95% CI 8–12), 23 (95% CI 18–33), and 16 months (95% CI 12–19), respectively. On multivariable Cox regression analysis, the pT3–4 stage, pN+ stage, and multifocal PSMs were independent predictors of LRFS, MRFS, RFS, and OS. Adjuvant chemotherapy improved all oncological outcomes studied (p < 0.05). The number of lymph nodes removed was independently associated with better LRFS, MRFS, and RFS. Advanced age at diagnosis was independently associated with worse OS. Conclusion: Patients with PSMs following RC have poor outcomes since half of them will recur within a year and will die of their disease. Among all PSMs types, patients with multifocal PSMs harbor the worst prognosis. We observed a benefit of adjuvant chemotherapy, but clinical trials evaluating innovative adjuvant strategies for these patients remain an unmet need.
An Update on the Metabolic Landscape of Oncogenic Viruses
Authors: Gaballah Ahmed , Bartosch Birke
Published: November 2022

Viruses play an important role in cancer development as about 12% of cancer types are linked to viral infections. Viruses that induce cellular transformation are known as oncoviruses. Although the mechanisms of viral oncogenesis differ between viruses, all oncogenic viruses share the ability to establish persistent chronic infections with no obvious symptoms for years. During these prolonged infections, oncogenic viruses manipulate cell signaling pathways that control cell cycle progression, apoptosis, inflammation, and metabolism. Importantly, it seems that most oncoviruses depend on these changes for their persistence and amplification. Metabolic changes induced by oncoviruses share many common features with cancer metabolism. Indeed, viruses, like proliferating cancer cells, require increased biosynthetic precursors for virion production, need to balance cellular redox homeostasis, and need to ensure host cell survival in a given tissue microenvironment. Thus, like for cancer cells, viral replication and persistence of infected cells frequently depend on metabolic changes. Here, we draw parallels between metabolic changes observed in cancers or induced by oncoviruses, with a focus on pathways involved in the regulation of glucose, lipid, and amino acids. We describe whether and how oncoviruses depend on metabolic changes, with the perspective of targeting them for antiviral and onco-therapeutic approaches in the context of viral infections.
Ten Years of CRISPRing Cancers In Vitro
Authors: Capoferri Davide , Filiberti Serena , Faletti Jessica , Tavani Camilla , Ronca Roberto
Published: November 2022

Cell lines have always constituted a good investigation tool for cancer research, allowing scientists to understand the basic mechanisms underlying the complex network of phenomena peculiar to the transforming path from a healthy to cancerous cell. The introduction of CRISPR in everyday laboratory activity and its relative affordability greatly expanded the bench lab weaponry in the daily attempt to better understand tumor biology with the final aim to mitigate cancer’s impact in our lives. In this review, we aim to report how this genome editing technique affected in the in vitro modeling of different aspects of tumor biology, its several declinations, and analyze the advantages and drawbacks of each of them.
Fabrication of a Plasmonic Heterojunction for Degradation of Oxytetracycline Hydrochloride and Removal of Cr(VI) from Water
Authors: Cao Jihui , Zhang Meihua , Yang Xinran , Zeng Xiaojun , Yang Yubo , Li Yuanyi , Zeng Hehua , Zhao Wei
Published: November 2022

A novel Ag/Ag2CO3/BiVO4 plasmonic photocatalyst was successfully prepared by depositing Ag nanoparticles on the surface of Ag2CO3/BiVO4 through the photoreduction reaction. Due to the existence of this novel heterojunction photocatalyst structure, not only can it prevent the photogenerated charge recombination, but the unique properties of Ag also have a great advantage in the absorption of light. The Ag/Ag2CO3/BiVO4 photocatalyst showed good catalytic performance in the degradation of oxytetracycline hydrochloride (OTH) and removal of Cr6+, and the degradation rate of OTH reached 98.0% after 150 min of illumination. The successful preparation of Ag/Ag2CO3/BiVO4 was confirmed by a series of characterization methods, and the importance of •OH and h+ radicals in the degradation of OTH was demonstrated. In addition, the photocatalytic mechanism of Ag/Ag2CO3/BiVO4 photocatalyst was systematically studied in terms of degradation of OTH and reduction of Cr6+. This study is of great importance for the development of novel plasmonic heterojunction photocatalysts and to meet future environmental requirements.
Efficacy and Safety of COVID-19 Vaccines—An Update
Authors: Sharma Eshani , Revinipati Sraddha , Bhandari Saisha , Thakur Sejal , Goyal Shubham , Ghose Aruni , Bajpai Sukrit , Muhammad Waleed , Boussios Stergios
Published: November 2022

A few centuries ago, the first vaccine vial was formulated, and since then, they have resulted in an eminent reduction in infectious diseases associated morbidity and mortality. The discovery of the novel SARS-CoV-2 virus and the COVID-19 disease and its steady progression to a global pandemic with 603,711,760 confirmed cases and 6,484,136 reported deaths according to the World Health Organization (WHO) on 7 September 2022 was exceedingly catastrophic. This brought about an unexpected need for preventative and cost-effective measures to curb the devastating impact of the virus, followed by accelerated competition within the pharma giants to manufacture and dispense vaccines at an exponential rate. Non-pharmaceutical medications such as mandated face mask policies, the imposition of travel limitations and generalized disinfectant use were somewhat successful in mitigating the catastrophic effect, but the onus fell upon vaccination strategies and other medical interventions to counteract and subdue this international health threat. The need to ensure current and future pandemic preparedness, however, presents multiple hurdles, among which are equitable vaccine access and the rising trend of vaccine hesitancy at an individual and international level, which are beyond the scope of this discussion. With this review article, we seek to draw perspective on current COVID-19 virus variants, in-hand vaccine types with their mechanism of action along with their effectiveness and safety profile. We also aim to discuss substantial side effects while adding a segment on the booster dose controversy.
Modeling Forest Fire Spread Using Machine Learning-Based Cellular Automata in a GIS Environment
Authors: Xu Yiqing , Li Dianjing , Ma Hao , Lin Rong , Zhang Fuquan
Published: November 2022

The quantitative simulation of forest fire spread is of great significance for designing rapid risk management approaches and implementing effective fire fighting strategies. A cellular automaton (CA) is well suited to the dynamic simulation of the spatiotemporal evolution of complex systems, and it is therefore used to model the complex process of forest fire spread. However, the process of forest fire spread is linked with a variety of mutually influencing factors, which are too complex to analyze using conventional approaches. Here, we propose a new method for modeling fire spread, namely LSSVM-CA, in which least squares support vector machines (LSSVM) is combined with a three-dimensional forest fire CA framework. In this approach, the effects of adjacent wind on the law of fire spread are considered and analyzed. The LSSVM is utilized to derive the complex state transformation rules for fire spread by training with a dataset based on actual local data. To validate the proposed model, the forest fire spread area simulated by LSSVM-CA and the actual extracted forest fire spread area were subjected to cross-comparison. The results show that LSSVM-CA performs well in simulating the spread of forest fire and determining the probability of forest fire.
Cloud-Native Applications and Services
Authors: Kratzke Nane
Published: November 2022

This Special Issue presents some of the most recent innovations in cloud-native software and system engineering practices providing a broad and well-grounded picture of what the more and more frequently used term “Cloud-native” is currently used for [...]
rl4dtn: Q-Learning for Opportunistic Networks
Authors: Visca Jorge , Baliosian Javier
Published: November 2022

Opportunistic networks are highly stochastic networks supported by sporadic encounters between mobile devices. To route data efficiently, opportunistic-routing algorithms must capitalize on devices’ movement and data transmission patterns. This work proposes a routing method based on reinforcement learning, specifically Q-learning. As usual in routing algorithms, the objective is to select the best candidate devices to put forward once an encounter occurs. However, there is also the possibility of not forwarding if we know that a better candidate might be encountered in the future. This decision is not usually considered in learning schemes because there is no obvious way to represent the temporal evolution of the network. We propose a novel, distributed, and online method that allows learning both the network’s connectivity and its temporal evolution with the help of a temporal graph. This algorithm allows learning to skip forwarding opportunities to capitalize on future encounters. We show that explicitly representing the action for deferring forwarding increases the algorithm’s performance. The algorithm’s scalability is discussed and shown to perform well in a network of considerable size.
YOLO-DFAN: Effective High-Altitude Safety Belt Detection Network
Authors: Yan Wendou , Wang Xiuying , Tan Shoubiao
Published: November 2022

This paper proposes the You Only Look Once (YOLO) dependency fusing attention network (DFAN) detection algorithm, improved based on the lightweight network YOLOv4-tiny. It combines the advantages of fast speed of traditional lightweight networks and high precision of traditional heavyweight networks, so it is very suitable for the real-time detection of high-altitude safety belts in embedded equipment. In response to the difficulty of extracting the features of an object with a low effective pixel ratio—which is an object with a low ratio of actual area to detection anchor area in the YOLOv4-tiny network—we make three major improvements to the baseline network: The first improvement is introducing the atrous spatial pyramid pooling network after CSPDarkNet-tiny extracts features. The second is to propose the DFAN, while the third is to introduce the path aggregation network (PANet) to replace the feature pyramid network (FPN) of the original network and fuse it with the DFAN. According to the experimental results in the high-altitude safety belt dataset, YOLO-DFAN improves the accuracy by 5.13% compared with the original network, and its detection speed meets the real-time demand. The algorithm also exhibits a good improvement on the Pascal voc07+12 dataset.
Pathophysiological Role and Diagnostic Potential of R-Loops in Cancer and Beyond
Authors: Khan Essak S. , Danckwardt Sven
Published: November 2022

R-loops are DNA–RNA hybrids that play multifunctional roles in gene regulation, including replication, transcription, transcription–replication collision, epigenetics, and preserving the integrity of the genome. The aberrant formation and accumulation of unscheduled R-loops can disrupt gene expression and damage DNA, thereby causing genome instability. Recent links between unscheduled R-loop accumulation and the abundance of proteins that modulate R-loop biogenesis have been associated with numerous human diseases, including various cancers. Although R-loops are not necessarily causative for all disease entities described to date, they can perpetuate and even exacerbate the initially disease-eliciting pathophysiology, making them structures of interest for molecular diagnostics. In this review, we discuss the (patho) physiological role of R-loops in health and disease, their surprising diagnostic potential, and state-of-the-art techniques for their detection.
Efficacy of Wholistic Turmeric Supplement on Adenomatous Polyps in Patients with Familial Adenomatous Polyposis—A Randomized, Double-Blinded, Placebo-Controlled Study
Authors: Gilad Ophir , Rosner Guy , Ivancovsky-Wajcman Dana , Zur Reut , Rosin-Arbesfeld Rina , Gluck Nathan , Strul Hana , Lehavi Dana , Rolfe Vivien , Kariv Revital
Published: November 2022

Several studies have demonstrated that curcumin can cause the regression of polyps in familial adenomatous polyposis (FAP), while others have shown negative results. Wholistic turmeric (WT) containing curcumin and additional bioactive compounds may contribute to this effect. We performed a double-blinded, randomized, controlled trial to assess the efficacy of WT in FAP patients. Ten FAP patients were randomly assigned to receive either WT or placebo for 6 months. Colonoscopies were performed at baseline and after 6 months. The polyp number and size, as well as the cumulative polyp burden, were assessed. No differences were noted between the groups in terms of changes from the baseline’s polyp number, size, or burden. However, stratifying the data according to the right vs. left colon indicated a decrease in the median polyp number (from 5.5 to 1.5, p = 0.06) and polyp burden (from 24.25 mm to 11.5 mm, p = 0.028) in the left colon of the patients in the WT group. The adjusted left polyp number and burden in the WT arm were lower by 5.39 (p = 0.034) and 14.68 mm (p = 0.059), respectively. Whether WT can be used to reduce the polyp burden of patients with predominantly left-sided polyps remains to be seen; thus, further larger prospective trials are required.
Mechanisms of EGFR-TKI-Induced Apoptosis and Strategies Targeting Apoptosis in EGFR-Mutated Non-Small Cell Lung Cancer
Authors: Nishihara Shigetoshi , Yamaoka Toshimitsu , Ishikawa Fumihiro , Higuchi Kensuke , Hasebe Yuki , Manabe Ryo , Kishino Yasunari , Kusumoto Sojiro , Ando Koichi , Kuroda Yusuke , Ohmori Tohru , Sagara Hironori , Yoshida Hitoshi , Tsurutani Junji
Published: November 2022

Homeostasis is achieved by balancing cell survival and death. In cancer cells, especially those carrying driver mutations, the processes and signals that promote apoptosis are inhibited, facilitating the survival and proliferation of these dysregulated cells. Apoptosis induction is an important mechanism underlying the therapeutic efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC). However, the mechanisms by which EGFR-TKIs induce apoptosis have not been fully elucidated. A deeper understanding of the apoptotic pathways induced by EGFR-TKIs is essential for the developing novel strategies to overcome resistance to EGFR-TKIs or to enhance the initial efficacy through therapeutic synergistic combinations. Recently, therapeutic strategies targeting apoptosis have been developed for cancer. Here, we review the state of knowledge on EGFR-TKI-induced apoptotic pathways and discuss the therapeutic strategies for enhancing EGFR-TKI efficiency. We highlight the great progress achieved with third-generation EGFR-TKIs. In particular, combination therapies of EGFR-TKIs with anti-vascular endothelial growth factor/receptor inhibitors or chemotherapy have emerged as promising therapeutic strategies for patients with EGFR-mutated NSCLC. Nevertheless, further breakthroughs are needed to yield an appropriate standard care for patients with EGFR-mutated NSCLC, which requires gaining a deeper understanding of cancer cell dynamics in response to EGFR-TKIs.
A Comprehensive Sequencing Analysis of Testis-Born miRNAs in Immature and Mature Indigenous Wandong Cattle (Bos taurus)
Authors: Liu Hongyu , Khan Ibrar Muhammad , Liu Yong , Khan Nazir Muhammad , Ji Kaiyuan , Yin Huiqun , Wang Wenliang , Zhou Xinqi , Zhang Yunhai
Published: November 2022

Micro RNAs (miRNAs) have been recognized as important regulators that are indispensable for testicular development and spermatogenesis. miRNAs are endogenous transcriptomic elements and mainly regulate the gene expression at post-transcriptional levels; however, the key role of miRNA in bovine testicular growth is not clearly understood. Thus, supposing to unveil the transcriptomics expression changes in the developmental processes of bovine testes, we selected three immature calves and three sexually mature bulls of the local Wandong breed for testicular-tissue sample collection. The cDNA libraries of experimental animals were established for RNA-sequencing analysis. We detected the miRNA expression in testes by using high-throughput sequencing technology, and bioinformatics analysis followed. The differentially expressed (DE) data showed that 151 miRNAs linked genes were significantly DE between immature and mature bull testes. Further, in detail, 64 were significantly up-regulated and 87 were down-regulated in the immature vs. mature testes (p-value < 0.05). Pathway analyses for miRNA-linked genes were performed and identified JAG2, BCL6, CFAP157, PHC2, TYRO3, SEPTIN6, and BSP3; these genes were involved in biological pathways such as TNF signaling, T cell receptor, PI3KAkt signaling, and functions affecting testes development and spermatogenesis. The DE miRNAs including MIR425, MIR98, MIR34C, MIR184, MIR18A, MIR136, MIR15A, MIR1388 and MIR210 were associated with cattle-bull sexual maturation and sperm production. RT-qPCR validation analysis showed a consistent correlation to the sequencing data findings. The current study provides a good framework for understanding the mechanism of miRNAs in the development of testes and spermatogenesis.
Previously Undescribed Gross HACE1 Deletions as a Cause of Autosomal Recessive Spastic Paraplegia
Authors: Kovalskaia Valeriia A. , Zabnenkova Victoriia V. , Petukhova Marina S. , Markova Zhanna G. , Tabakov Vyacheslav Yu. , Ryzhkova Oxana P.
Published: November 2022

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS, OMIM 616756) is a rare genetic disease caused by biallelic pathogenic variants in the HACE1 gene. Originally, these mutations have been reported to be implicated in tumor predisposition. Nonetheless, via whole exome sequencing in 2015, HACE1 mutations were suggested to be the cause of a new autosomal recessive neurodevelopmental disorder, which is characterized by spasticity, muscular hypotonia, and intellectual disability. To date, 14 HACE1 pathogenic variants have been described; these variants have a loss-of-function effect that leads to clinical presentations with variable severities. However, gross deletions in the HACE1 gene have not yet been mentioned as a cause of spastic paraplegia. Here, we report a clinical case involving a 2-year-old male presenting with spasticity, mainly affecting the lower limbs, and developmental delay. Exome sequencing, chromosomal microarray analysis, and mRNA analysis were used to identify the causative gene. We revealed that the clinical findings were due to previously undescribed HACE1 biallelic deletions. We identified the deletion of exon 7: c.(534+1_535-1)_(617+1_618-1)del (NM_020771.4) and the gross deletion in the 6q16.3 locus, which affected the entire HACE1 gene: g.105018931_105337494del, (GRCh37). A comprehensive diagnostic approach for the patients with originally homozygous mutations in HACE1 is required since false homozygosity results are possible. More than 80% of the described mutations were reported to be homozygous. Initial hemizygosity is hard to detect by quantitative methods, and this may challenge molecular diagnostic identification in patients with spastic paraplegia.
Psychosocial Support Programme Improves Adherence and Health Systems Experiences for Adolescents on Antiretroviral Therapy in Mpumalanga Province, South Africa
Authors: Okonji Emeka , Wyk Brian , Hughes Gail , Mukumbang Ferdinand
Published: November 2022

(1) Background: Psychosocial support (PSS) plays a significant role in persistent adherence to and retention in antiretroviral therapy (ART) for adolescents living with the human immunodeficiency virus (ALHIV). This paper qualitatively explores the experiences of ALHIV on ART, who participated in a PSS programme in five public primary healthcare facilities in Mpumalanga Province in South Africa during the COVID-19 pandemic. (2) Methods: Data were collected through 24 focus group discussions with 173 ALHIV on ART and subjected to inductive thematic analysis. Informed consent was obtained before all data collection. (3) Results: The PSS programme facilitated the process of full HIV disclosure to these adolescents with the support of parents/guardians while motivating adherence through peer support groups and health education for improved treatment literacy. Participants reported positive health systems experiences, improved healthcare provider–client relations, and prompt access to health services. (4) Conclusions: The PSS programme successfully kept ALHIV engaged in ART care despite the health service disruptions encountered during the COVID-19 pandemic. We recommend rigorous evaluation of the effects of the PSS intervention on adherence to and retention in ART among ALHIV in HIV-endemic settings.
Measuring Family Quality of Life: Scoping Review of the Available Scales and Future Directions
Authors: Alnahdi Ghaleb H. , Alwadei Arwa , Woltran Flora , Schwab Susanne
Published: November 2022

The lack of quality of life is a key issue for families with children with an intellectual disability. While the quality of life for people with disabilities has previously been researched as an individual variable, this has now shifted to include family members. The purpose of this study was to conduct a review of the studies measuring the quality of life of families with an intellectually disabled member, in order to identify the most commonly used scales and their psychometric properties. Method: Data were collected from six databases (ERIC, Web of Science, Scopus, CINAHL, MedLine, and Google Scholar), and this search yielded 3948 studies. One hundred and twenty studies that met the inclusion criteria were included in this study. Results: Nine scales were used in the last years to measure the quality of life for families with individuals with an intellectual disability. The Beach Center scale was the most common scale, followed by the Family Quality of Life Survey and the World Health Organization’s quality of life assessment (WHOQoL-BREF). The results showed that the included studies in the review lack the consideration of a broader population representing the different types of cultures with different socioeconomic backgrounds. Key aspects used to assess the FQoL are environmental factors (proximal and distal factors), as well as economic factors. Conclusion: Although the operationalization of the FQoL often incudes several subthemes, a general agreement regarding which domains of the FQoL need to be included in the measurements, and these do not exist right now. Moreover, multidimensional scales are still rare.
Evaluating the Spatiotemporal Characteristics of Agricultural Eco-Efficiency Alongside China’s Carbon Neutrality Targets
Authors: Cheng Changming , Li Jieqiong , Qiu Yuqing , Gao Chunfeng , Gao Qiang
Published: November 2022

Agriculture has the dual effect of contributing to both carbon emissions and sequestration, and thus plays a critical role in mitigating global climate change and achieving carbon neutrality. Agricultural eco-efficiency (AEE) is an important measurement through which we can assess the efforts toward reduced emissions and increased sequestration. The purpose of this study was to understand the relationship between China’s target of carbon neutrality and AEE through an evaluative model, so as to improve AEE and ultimately achieve sustainable agricultural development. The Super-SBM model scientifically measures the AEE based on provincial panel data collected between 2000 and 2020. We selected kernel density function and spatial distribution to explore the spatial and temporal evolutionary trends, and used a Tobit model to identify the drivers of AEE. The research shows that (1) China’s agricultural system functions as a net carbon sink, with all provinces’ agricultural carbon sequestration levels recorded as higher than their carbon emissions from 2000 to 2020. (2) Despite sequestration levels, the level of AEE in China is not high enough, and the average efficiency level from 2000 to 2020 is 0.7726, showing an overall trend where AEE decreased at first and then increased. (3) The AEE of each province is clearly polarized; there are obvious core–periphery characteristics and spatial distribution of clustered contiguous areas. Central provinces generally have lower efficiency, eastern and northeastern provinces have higher efficiency, and northeastern provinces always remain in the high-efficiency group. (4) Influencing factors show that urbanization, upgrading of industrial structure, financial support for agriculture, and mechanization have a significant positive impact on AEE. These findings have important implications for the promotion of the low-carbon green development of Chinese agriculture.
Physicians’ Perspectives Regarding Private Equity Transactions in Outpatient Health Care—A Scoping Review and Qualitative Analysis
Authors: Nolte Tim N. , Miedaner Felix , Sülz Sandra
Published: November 2022

Private equity (PE) investments in health care have increased drastically over the last decade, and the profit interests of these companies have triggered a vivid discussion among medical professions. However, what are the key underlying perceptions among physicians regarding this trend? Unravelling the argumentative structure of this debate is the purpose of this paper. With physicians being a major stakeholder group in the outpatient health care setting, this paper explores physicians’ perspectives regarding increasing PE activities. We systematically searched, selected, and synthesized existing knowledge in a scoping review and complemented the findings through 14 semi-structured interviews with physicians working in the outpatient health care sector in Germany. The results outline a complex network of arguments, concerns, and fears whereby the first intuitive perception of physicians is of critical nature. Arguments cluster around central perceptions of how PE involvement affects the individual autonomy of physicians in their daily work and decision-making, the impact on quality of care, work-life balance considerations, PE investment strategies, lack of medical vs. managerial expertise, and taxation issues. The high number of opinion papers among the literature underlines the actuality of the topic and emphasizes the need for empirical research.
Multidimensional Environmental Factors and Sleep Health for Aging Adults: A Focused Narrative Review
Authors: Yang Eunhwa , Ismail Aliaa , Kim Yujin , Erdogmus Ece , Boron Julie , Goldstein Felicia , DuBose Jennifer , Zimring Craig
Published: November 2022

The timing, amount, and quality of sleep are critical for an individual’s health and quality of life. This paper provides a focused narrative review of the existing literature around multidimensional environments and sleep health for aging adults. Five electronic databases, Scopus, Web of Science, PubMed/Medline; EBSCOhost, PsycINFO (ProQuest), and Google Scholar yielded 54,502 total records. After removing duplicates, non-peer reviewed academic articles, and nonrelevant articles, 70 were included for review. We were able to categorize environmental factors into housing security, home environment, and neighborhood environment, and, within each environmental category, specific elements/aspects are discussed. This paper provides a comprehensive map connecting identified levels of influence (individual, home/house, and neighborhood-level) in which subfactors are listed under each level of influence/category with the related literature list. Our review highlights that multidimensional environmental factors can affect aging adults’ sleep health and eventually their physical, mental, and cognitive health and that sleep disparities exist in racial minorities in socioeconomically disadvantaged communities in which cumulative environmental stressors coexist. Based on this focused narrative review on the multidimensional sleep environments for aging adults, knowledge gaps are identified, and future research directions are suggested.
Abnormal Regional Spontaneous Neural Activity and Functional Connectivity in Unmedicated Patients with Narcolepsy Type 1: A Resting-State fMRI Study
Authors: Wu Lanxiang , Zhan Qingqing , Liu Qian , Xie Suheng , Tian Sheng , Xie Liang , Wu Wei
Published: November 2022

Background: Previous Resting-state functional magnetic resonance imaging (fMRI) studies have mainly focused on cerebral functional alteration in processing different emotional stimuli in patients with narcolepsy type 1 (NT1), but were short of exploration of characteristic brain activity and its remote interaction patterns. This study aimed to investigate the spontaneous blood oxygen fluctuations at rest and to elucidate the neural mechanisms underlying neuropsychiatric behavior. Method: A total of 18 unmedicated patients with NT1 and matched healthy individuals were recruited in a resting-state fMRI study. Magnetic resonance imaging (MRI) data were first analyzed using fractional low-frequency amplitude of low-frequency fluctuation (fALFF) to detect changes in local neural activity, and regions with group differences were taken as regions of interest (ROIs). Secondly, functional connectivity (FC) analysis was used to explore altered connectivity between ROIs and other areas. Lastly, the relationship between functional brain activity and neuropsychiatric behaviors was analyzed with correlation analysis. Results: fALFF analysis revealed enhanced neural activity in bilateral fusiform gyrus (FFG), right precentral gyrus, and left postcentral gyrus (PoCG) in the NT1 group. The patients indicated reduced activity in the bilateral temporal pole middle temporal gyrus (TPOmid), left caudate nucleus (CAU), left parahippocampus, left precuneus (PCUN), right amygdala, and right anterior cingulate and paracingulate gyri. ESS score was negatively correlated with fALFF in the right FFG. The NT1 group revealed decreased connectivity between left TPOmid and right PoCG, the bilateral middle frontal gyrus, left superior frontal gyrus, medial, and right supramarginal gyrus. Epworth Sleepiness Scale (ESS) was negatively correlated with FC of the left TPOmid with left putamen (PUT) in NT1. Compared with healthy controls (HCs), enhanced FC of the left CAU with right FFG was positively associated with MSLT-SOREMPs in patients. Furthermore, increased FC of the left PCUN with right PoCG was positively correlated with SDS score. Conclusions: We found that multiple functional activities related to the processing of emotional regulation and sensory information processing were abnormal, and some were related to clinical characteristics. fALFF in the left postcentral or right precentral gyrus may be used as a biomarker of narcolepsy, whereas fALFF in the right fusiform and the FC strength of the left temporal pole middle temporal gyrus with the putamen may be clinical indicators to assess the drowsiness severity of narcolepsy.
Intermittent Use of Anti-Hormonal Agents for the Endocrine Therapy of Sex-Hormone-Dependent Breast and Prostate Cancer: A Protocol for a Systematic Review
Authors: Kesztyüs Dorothea , Kämpfer Johanna , Kesztyüs Tibor
Published: November 2022

Therapies with the continuous administration of anti-hormonal agents in sex-hormone-dependent malignancies such as prostate and breast carcinomas often lead to the development of resistant tumor cells. A systematic evaluation of the use and effects of the intermittent application of endocrine therapy could provide information on the state of knowledge in this research area. PubMed, Cochrane Library, Embase, and Web of Science will be systematically searched using pretested search strategies. Randomized and non-randomized controlled trials, pragmatic trials, case–control, and comparative cohort studies will be eligible. Primary outcomes will be progression-free survival, disease-free survival, and overall survival. The literature retrieved will be selected based on predefined inclusion and exclusion criteria. Relevant data will be extracted from included references into a pre-designed table. The risk of bias will be assessed, and the report of the results will follow PRISMA recommendations and include any deviations from this protocol. The increasing prevalence of breast and prostate cancer and limitations of current therapeutic approaches require a closer look at alternatives. Additionally, to explore new therapeutic agents, modalities of administration should be rigorously reviewed to determine the best regimens for patients. This proposed systematic review aims to summarize and evaluate the current knowledge regarding intermittent endocrine cancer therapy to provide a basis for further research.
Changes in DNA Methylation of Clock Genes in Obese Adolescents after a Short-Term Body Weight Reduction Program: A Possible Metabolic and Endocrine Chrono-Resynchronization
Authors: Rigamonti Antonello E. , Bollati Valentina , Favero Chiara , Albetti Benedetta , Caroli Diana , De Col Alessandra , Cella Silvano G. , Sartorio Alessandro
Published: November 2022

Circadian rhythms are generated by a series of genes, collectively named clock genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including metabolism and the endocrine system, are regulated by clock genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven clock genes, namely clock, arntl, per1-3 and cry1-2, in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 [2.76; 3.12]) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo–pituitary–adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of clock, cry2 and per2 genes occurred in the entire population, together with hypermethylation of clock and per3 genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some clock genes. Finally, BWRP induced changes in clock genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific clock genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a “biomolecular” predictor of successful antiobesity intervention.
IvCDS: An End-to-End Driver Simulator for Personal In-Vehicle Conversational Assistant
Authors: Ji Tianbo , Yin Xuanhua , Cheng Peng , Zhou Liting , Liu Siyou , Bao Wei , Lyu Chenyang
Published: November 2022

An advanced driver simulator methodology facilitates a well-connected interaction between the environment and drivers. Multiple traffic information environment language processing aims to help drivers accommodate travel demand: safety prewarning, destination navigation, hotel/restaurant reservation, and so on. Task-oriented dialogue systems generally aim to assist human users in achieving these specific goals by a conversation in the form of natural language. The development of current neural network based dialogue systems relies on relevant datasets, such as KVRET. These datasets are generally used for training and evaluating a dialogue agent (e.g., an in-vehicle assistant). Therefore, a simulator for the human user side is necessarily required for assessing an agent system if no real person is involved. We propose a new end-to-end simulator to operate as a human driver that is capable of understanding and responding to assistant utterances. This proposed driver simulator enables one to interact with an in-vehicle assistant like a real person, and the diversity of conversations can be simply controlled by changing the assigned driver profile. Results of our experiment demonstrate that this proposed simulator achieves the best performance on all tasks compared with other models.
How to Better Integrate Social Determinants of Health into Primary Healthcare: Various Stakeholders’ Perspectives
Authors: Hudon Catherine , Dumont-Samson Olivier , Breton Mylaine , Bourgueil Yann , Cohidon Christine , Falcoff Hector , Senn Nicolas , Van Durme Thérèse , Angrignon-Girouard Émilie , Ouadfel Sarah
Published: November 2022

This paper aims to identify challenges and opportunities related to the integration of social determinants of health (SDH) into primary healthcare at an international symposium in Orford, Quebec, Canada. A descriptive qualitative approach was conducted. Three focus groups on different topics were led by international facilitators. Two research team members took notes during the focus groups. All the material was analyzed using a thematic analysis according to an inductive method. Many challenges were identified, leading to the identification of potential opportunities: integrate the concept of SDH in all phases of the training curriculum for health professionals to foster interprofessional and intersectoral collaboration and sociocultural skills; organize healthcare for better outreach to vulnerable populations; organize local and regional committees to develop management frameworks to produce and use territory-specific data; develop dashboards for primary healthcare providers describing the composition of their territory’s population; work collaboratively, rallying primary healthcare providers, community organization delegates, patient partners, citizens, and municipality representatives around common projects. Discussions prompted new directions for further primary healthcare research, among which are building on best practices in the literature and in the field, and engaging various stakeholders in research, including vulnerable populations, while focusing on patient experience.
Brain Fog and Fatigue following COVID-19 Infection: An Exploratory Study of Patient Experiences of Long COVID
Authors: Chasco Emily E. , Dukes Kimberly , Jones DeShauna , Comellas Alejandro P. , Hoffman Richard M. , Garg Alpana
Published: November 2022

Post-acute sequelae of SARS-CoV-2 (PASC) is a poorly understood condition with significant impact on quality of life. We aimed to better understand the lived experiences of patients with PASC, focusing on the impact of cognitive complaints (“brain fog”) and fatigue on (1) daily activities, (2) work/employment, and (3) interpersonal relationships. We conducted semi-structured qualitative interviews with 15 patients of a Midwestern academic hospital’s post-COVID-19 clinic. We audio-recorded, transcribed, and analyzed interviews thematically using a combined deductive-inductive approach and collected participants’ characteristics from chart review. Participants frequently used descriptive and metaphorical language to describe symptoms that were relapsing-remitting and unpredictable. Fatigue and brain fog affected all domains and identified subthemes included symptoms’ synergistic effects, difficulty with multitasking, lack of support, poor self-perception, and fear of loss of income and employment. Personal relationships were affected with change of responsibilities, difficulty parenting, social isolation, and guilt due to the burdens placed on family. Furthermore, underlying social stigma contributed to negative emotions, which significantly affected emotional and mental health. Our findings highlight PASC’s negative impact on patients’ daily lives. Providers can better support COVID-19 survivors during their recovery by identifying their needs in a sensitive and timely manner.
Investigating the Usage Patterns of Park Visitors and Their Driving Factors to Improve Urban Community Parks in China: Taking Jinan City as an Example
Authors: Kong Deyi , Chen Zujian , Li Cheng , Fei Xinhui
Published: November 2022

Urban community parks have significant benefits for city residents, both physical and spiritual. This is especially true in developing countries, such as China. The purpose of our study is to describe the current situation of the community parks in five main districts of Jinan City while recognizing features of the community parks that influence usage patterns. Our study also means to determine the desired improvements of visitors that promote access to and use of community parks on the basis of the Chinese context. We conducted a survey among 542 community park visitors and obtained valid responses. The findings of respondents show that community parks are mostly used by people over 55 years (34.7%) and children under 10 years (23.6%). The main motives for using community parks are for exercise (24.2%) and to socialize with others (21.6%). The majority of respondents (65.7%) rated the community park as satisfactory and considered only a few improvements needed. Regarding the desired improvements, numerous respondents mentioned adding more physical training facilities (13.3%) and activity areas (7.6%), as well as emergency call buttons in areas frequented by children and older people (7.6%). Furthermore, most of the respondents (79.9%) indicated that they would like to use the community parks more frequently if there is additional progress to make the parks more attractive, cleaner, and friendlier. These results can help park designers, government agencies, and community groups to provide the planning and design strategies for community parks to promote their upgrading in China.
Criteria and Guidelines for Human-Centered Work Design in a Digitally Transformed World of Work: Findings from a Formal Consensus Process
Authors: Tegtmeier Patricia , Weber Corinna , Sommer Sabine , Tisch Anita , Wischniewski Sascha
Published: November 2022

With the increasing digital transformation, work tasks are changing—in some cases, significantly. Our study addresses the question of whether the established criteria for work design are still sufficient or if they should get updated and additional criteria become necessary in the context of digitalization. In a multistage consensus process involving interdisciplinary groups of experts, we have identified specific criteria for the humane design of work in a world increasingly permeated by digitalized work tools. Starting with an expert workshop using a combined nominal group/focus group technique, followed by a real-time Delphi study, a content analysis and a five-stage peer comment process, we detected 13 criteria and 38 design guidelines for human-centered work in digital transformation. Mapping these with established criteria, it became apparent that some established criteria have experienced a new dynamic because of the digital transformation. For other criteria, a need for digitization-sensitive design is discernible. In addition, criteria have emerged whose necessity is rooted in the digital transformation. A diffusion and stronger interconnection of the various levels of the work system in connection with the digital transformation of work is apparent.
Hierarchical Analysis of Forms of Support for Employees in the Field of Health Protection and Quality of Work during the COVID-19 Pandemic and the Desired Post-Pandemic Forms of Support
Authors: Dembińska Izabela , Barczak Agnieszka , Rostkowski Tomasz , Kauf Sabina , Marska-Dzioba Natalia
Published: November 2022

Issues of employee support during the COVID-19 pandemic and the post-pandemic period are of an interdisciplinary nature. Moreover, these should be considered from both an epistemological and a practical perspective. The aim of this study was to determine what forms of support for employees in terms of health and quality of work were provided by employers during the pandemic and what forms of support will be expected by employees after it ceases. The research process was carried out in two stages: primary and secondary exploration and quantitative clarification. In the first stage, a systematic review of the literature and a critical analysis of the so-called grey literature was performed. In the second stage, computer-assisted telephone interview (CATI) methodology was used. Ward’s method was used for data analysis. The results showed that the COVID-19 pandemic forced employers to search for new solutions to enable the continuation of their business activities, which consisted of switching from the traditional form of work to a remote form. The transition to the remote work mode changed the approach to the forms of work support provided for employees, with particular emphasis on the health of employees and the quality of work. The changes in the forms of support for employees in terms of health and quality of work were either bottom-up or top-down. Employers tried to provide access to remote infrastructure as much as possible, but the consequences of remote work in terms of the physical and mental health of employees were rarely noticed or considered. After the pandemic, online health support and access to the appropriate equipment and tools for remote work are unlikely to be needed.