bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolving scenario of cancer care provision across the COVID-19 pandemic in Europe
Authors: Tagliamento Marco , Poggio Francesca , Perachino Marta , Pirrone Chiara , Fregatti Piero , Lambertini Matteo 
Published: August 2022

Purpose of review
Over the past 2 years, the COVID-19 pandemic has had short-term and long-term effects on the delivery of cancer care. Some European countries faced an unprecedented widespread crisis during the first year of the SARS-CoV-2 pandemic, only being able afterwards to gradually recover, thanks to the improvement in preventive measures, changes in public health and reactive processes in cancer care and a better understanding of the ongoing heath emergency.

Recent findings
The development of SARS-CoV-2 vaccines and COVID-19 specific treatments, the growing testing and tracking capability to limit virus diffusion, and research efforts to better define areas of action have all greatly limited the negative impact of the health emergency on routine cancer care.
The need to protect those more vulnerable and to ensure continuity of care for oncology patients has been balanced across the pandemic, with the aim to guarantee an optimal standard of care.

Summary
This article aims to provide an overview on the evolving scenario of cancer care throughout the COVID-19 pandemic in Europe, focusing on the particular features that characterized the pandemic course as well as the main differences that were observed across it.
Assessment of the Optic Disc and Retinal Microvasculature by Optical Coherence Tomography Angiography in Patients With Pediatric Migraine
Authors: Kurtul Bengi Ece , Sipal Cansu , Akbas Yilmaz 
Published: August 2022

Background:
Migraine, as a chronic neurovascular disease, is known to be a risk factor for retinal and optic nerve head damage. Herein, we aimed to evaluate the optic disc and retinal microvasculature in pediatric migraine (PM) patients using optical coherence tomography angiography (OCTA).

Methods:
Forty-six eyes of 23 patients with PM without aura (PM group) and 46 eyes of 23 age- and sex-matched healthy subjects (control group) were included in this cross-sectional prospective study. Demographic features and ophthalmological examination including OCTA measurements were evaluated. OCTA was performed with 6- × 6-mm sections for macula and 4.5- × 4.5-mm sections for optic nerve head in all eyes. Foveal retinal thickness (FRT), peripapillary retinal nerve fiber layer (RNFL) thickness, vessel density in different sections of the retina, and optic disc were analyzed and compared between the groups. All measurements of the PM patients were taken in the attack-free period.

Results:
The mean ages of the PM group and control group were 11.17 ± 3.3 and 11.83 ± 2.8 years, respectively (P = 0.479). Gender and mean intraocular pressures were similar between the groups. The mean central corneal thickness levels in the PM group were significantly lower than control group, 548.28 ± 26.3 µm and 562.04 ± 24.5 µm, respectively (P = 0.011). There was no significant difference regarding average and all quadrant RNFL thicknesses, foveal avascular zone and flow areas, deep vessel densities, and optic disc capillary densities between the groups. However, compared with the control group, the PM group showed significant higher values of FRT, and lower values of superficial whole and parafoveal vessel densities (247.28 ± 15.8 µm vs 285.93 ± 11.1, P < 0.001, 51.85 ± 2.4% vs 50.31 ± 4.0%, P = 0.02, 55.09 ± 2.3% vs 53.5 ± 3.5%, P = 0.01, respectively). Disease duration and attacks/year did not show any significant correlations with OCTA values.

Conclusions:
PM seems to be associated with lower superficial whole and parafoveal vessel densities because of hypoperfusion and ischemia. OCTA may be suggested for use in follow-up and management of PM patients.
Optimal drug treatment for reducing long-term drug resistance
Authors: Ghodsi Asnaashari Tina , Chang Young Hwan 
Published: August 2022

AbstractThe maximum-tolerated dose principle, the highest possible drug dose in the shortest possible time period, has been the standard care for cancer treatment. Although it is appealing in a homogeneous tumor settings, tumor heterogeneity and adaptation play a significant role in driving treatment failure. They are still major obstacles in cancer treatments despite great advances in modeling and cancer therapy using optimal control theory. To address this, we first generalize two population models and examine the long-term effects of differential selective treatment strategies. Second, we take into account different drug-imposed selective pressure into designing optimal treatment strategies. Numerical examples demonstrate that the proposed treatment strategy decreases long-term tumor burden by decreasing the rate of tumor adaptation.
Eco-evolutionary feedback can stabilize diverse predator-prey communities
Authors: Martis Stephen 
Published: August 2022

AbstractEcological models with random interactions have provided insight into the problem of diversity, particularly showing that high variance in the distribution of interaction rates can lead to instability, chaos and extinction. However, these models have traditionally neglected evolution, which is central to the generation of biological variation and can act on timescales comparable to ecological change. We demonstrate that when a stochastic predator-prey system is coupled to high-dimensional evolutionary dynamics, high variance interactions counter-intuitively stabilize the population, delaying extinction and increasing the total population size. Using both stochastic and deterministic simulations and theory based on the statistical physics of disordered systems, this stabilizing effect is shown to be driven by an eco-evolutionary feedback loop which causes the population size to grow as a power law of the variance of the interactions. We show that the stable regime corresponds with the clonal interference regime of population genetics. We conjecture that qualitative aspects of our results generalize to other evolving complex systems.
Impact of diabetes on longevity and disability-free life expectancy among older South African adults: a prospective longitudinal analysis
Authors: Payne Collin F. , Liwin Lilipramawanty K. , Wade Alisha N. , Houle Brian , Du Toit Jacques D. , Flood David , Manne-Goehler Jennifer 
Published: August 2022

AbstractObjectiveWe seek to understand the coexisting effects of population aging and a rising burden of diabetes on healthy longevity in South Africa.Research Design and MethodsWe used longitudinal data from the 2015 and 2018 waves of the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI) study to explore life expectancy (LE) and disability-free life expectancy (DFLE) of adults aged 45 and older with and without diabetes in rural South Africa. We estimated LE and DFLE by diabetes status using Markov-based microsimulation.ResultsWe find a clear gradient in remaining LE and DFLE based on diabetes status. At age 45, a man without diabetes could expect to live 7.4 [95% CI 3.4 – 11.7] more years than a man with diabetes, and a woman without diabetes could expect to live 3.9 [95% CI: 0.8 – 6.9] more years than a woman with diabetes. Individuals with diabetes lived proportionately more years subject to disability than individuals without diabetes. Additional analyses separating individuals with diabetes based on whether they knew their disease status found that individuals with diabetes diagnosed by a healthcare worker had shorter remaining LE than those who were unaware of their status or those without diabetes.ConclusionsOur findings highlight the large and important decrements in healthy, disability-free aging for people with diabetes in South Africa. This finding should motivate efforts to strengthen prevention and treatment efforts for diabetes and its complications for older adults in this setting.
Deep Learning for Automatic Segmentation of Vestibular Schwannoma: A Retrospective Study from Multi-Centre Routine MRI
Authors: Kujawa Aaron , Dorent Reuben , Connor Steve , Thomson Suki , Ivory Marina , Vahedi Ali , Guilhem Emily , Wijethilake Navodini , Bradford Robert , Kitchen Neil , Bisdas Sotirios , Ourselin Sebastien , Vercauteren Tom , Shapey Jonathan 
Published: August 2022

ABSTRACTAutomatic segmentation of vestibular schwannoma (VS) from routine clinical MRI has potential to improve clinical workflow, facilitate treatment decisions, and assist patient management. Previous work demonstrated reliable automatic segmentation performance on datasets of standardised MRI images acquired for stereotactic surgery planning. However, diagnostic clinical datasets are generally more diverse and pose a larger challenge to automatic segmentation algorithms, especially when post-operative images are included. In this work, we show for the first time that automatic segmentation of VS on routine MRI datasets is also possible with high accuracy.We acquired and publicly release a curated multi-centre routine clinical (MC-RC) dataset of 160 patients with a single sporadic VS. For each patient up to three longitudinal MRI exams with contrast-enhanced T1-weighted (ceT1w) (n=124) and T2-weighted (T2w) (n=363) images were included and the VS manually annotated. Segmentations were produced and verified in an iterative process: 1) initial segmentations by a specialized company; 2) review by one of three trained radiologists; and 3) validation by an expert team. Inter- and intra-observer reliability experiments were performed on a subset of the dataset. A state-of-the-art deep learning framework was used to train segmentation models for VS. Model performance was evaluated on a MC-RC hold-out testing set, another public VS datasets, and a partially public dataset.The generalizability and robustness of the VS deep learning segmentation models increased significantly when trained on the MC-RC dataset. Dice similarity coefficients (DSC) achieved by our model are comparable to those achieved by trained radiologists in the inter-observer experiment. On the MC-RC testing set, median DSCs were 86.2(9.5) for ceT1w, 89.4(7.0) for T2w and 86.4(8.6) for combined ceT1w+T2w input images. On another public dataset acquired for Gamma Knife stereotactic radiosurgery our model achieved median DSCs of 95.3(2.9), 92.8(3.8), and 95.5(3.3), respectively. In contrast, models trained on the Gamma Knife dataset did not generalise well as illustrated by significant underperformance on the MC-RC routine MRI dataset, highlighting the importance of data variability in the development of robust VS segmentation models.The MC-RC dataset and all trained deep learning models were made available online.
MitoStores: Chaperone-controlled protein granules store mitochondrial precursors in the cytosol
Authors: Krämer Lena , Dalheimer Niko , Räschle Markus , Storchová Zuzana , Pielage Jan , Boos Felix , Herrmann Johannes M. 
Published: August 2022

AbstractHundreds of mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational reaction. The early processes associated with mitochondrial protein targeting remain poorly understood. Here we show that in baker’s yeast, the cytosol has the capacity to transiently store matrix-destined precursors in dedicated deposits which we named MitoStores. MitoStores are strongly enhanced when protein import into mitochondria is competitively inhibited by a clogging of mitochondrial import sites, but also formed under physiological conditions when cells grow on non-fermentable carbon sources. MitoStores are enriched for a specific subset of nuclear encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. MitoStore formation is controlled by the heat shock proteins Hsp42 and Hsp104, potentially to suppress the toxic potential of accumulating mitochondrial precursor proteins. Thus, the cytosolic protein quality control system plays an active role during early stages in mitochondrial protein targeting by the coordinated and localized sequestration of mitochondrial precursor proteins.SummaryThe yeast cytosol can deposit precursors of mitochondrial proteins in specific granules called MitoStores. MitoStores are controlled by the cytosolic chaperone system, in particular by Hsp42 and Hsp104. MitoStore formation suppresses the toxicity arising from non-imported mitochondrial precursor proteins.
Fiber Diameter and Architecture Direct Three-Dimensional Assembly of Pericytes into Spheroids
Authors: Sharma Sharan , Hill Jennifer C. , Phillippi Julie A. , Nain Amrinder S. 
Published: August 2022

AbstractDue to their physiological relevance, multicellular 3D spheroids are actively replacing standard 2D monolayer cultures. How spheroids are formed through the assembly of individual cells in natural fibrous environments that include a mix of diameters and architectures in vivo remains unknown. Here, we demonstrate that the spontaneous assembly of human vasa vasorum-derived pericytes in 3D spheroids depends on the fiber diameter and network architecture. A parallel arrangement of suspended fibers of all tested diameters (200, 500, and 800 nm) leads to the formation of spheroids, while on crosshatch networks, spheroid assembly on larger diameters is absent. The design of fibrous networks of a mix of diameters and architectures leads to the patterning of spheroids in desired locations. Fiber remodeling in parallel arrangements serves as force sensors providing mechanical insights into the assembly dynamics of spheroids and subsequent cell sprouting from spheroids. Translocation and merger of spheroids occur predominantly on parallel fiber networks, while on crosshatch networks, a cellular exchange is observed between spheroids connected with remodeled fibers. Rho kinase inhibition by Y27632 and subsequent wash-off leads to spheroid disintegration and reassembly, thus, highlighting the role of cell contractility in the assembly and integrity of 3D spheroids. Overall, using extracellular mimicking fiber networks of varying diameters and architectures, we report new insights into the 3D dynamics of spheroids which may inform pericyte’s role in vasculogenesis, and (patho)physiological angiogenesis
Exploiting the Nonlinear Structure of the Antithetic Integral Controller to Enhance Dynamic Performance
Authors: Filo Maurice , Kumar Sant , Anastassov Stanislav , Khammash Mustafa 
Published: August 2022

AbstractThe design of biomolecular feedback controllers has been identified as an important goal across a broad range of biological applications spanning synthetic biology, cell therapy, metabolic engineering, etc. This originates from the need to regulate various cellular processes in a robust and timely fashion. Recently, antithetic integral controllers found their way into synthetic biology due to the Robust Perfect Adaptation (RPA) property they endow — the biological analogue of robust steady-state tracking. The antithetic integral motif hinges on a sequestration reaction between two molecules that annihilates their function. Here, we demonstrate that the complex resulting from the nonlinear sequestration reaction can be leveraged as an inhibitor to enhance the dynamic performance while maintaining the RPA property. We establish that this additional inhibition by the sequestration complex gives rise to a filtered Proportional-Integral (PI) controller thus offering more flexibility in shaping the dynamic response and reducing cell-to-cell variability. Furthermore, we explore the effect of various biological inhibitory mechanisms on the overall performance. The various analyses in the paper are carried out using analytical tools and are supported by numerical simulations. Finally, an experimental validation is performed using the cyberloop — a hybrid platform where the controller is implemented in silico to control a genetic circuit in vivo.
Water salinity does not affect acute thermal tolerance (CTmax) in zebrafish (Danio rerio)
Authors: Åsheim Eirik R. , Andreassen Anna H. , Morgan Rachael , Silvestre Mireia , Jutfelt Fredrik 
Published: August 2022

ABSTRACTTolerance against acute warming is an essential trait that can determine how organisms cope during heatwaves, yet the mechanisms underlying it remain elusive. Water salinity has previously been shown to modulate thermal tolerance and may therefore provide clues towards these limiting mechanisms. Here we tested whether short (2 hours) and long (10 days) term exposure to different water salinities (0-5 ppt) affected acute thermal tolerance in zebrafish (N=269). We found that water salinity did not affect the thermal tolerance of zebrafish at either time point, indicating that salinity does not affect the mechanism limiting acute thermal tolerance limits in zebrafish. We did, however, observe unexpected behaviour during the CTmax test in a subset of fish in the highest salinity treatment after 10 days (3 ppt), indicating some form of salinity-driven disturbance during warming.
Longitudinal metatranscriptomic sequencing of Southern California wastewater representing 16 million people from August 2020-21 reveals widespread transcription of antibiotic resistance genes
Authors: Rothman Jason A. , Saghir Andrew , Chung Seung-Ah , Boyajian Nicholas , Dinh Thao , Kim Jinwoo , Oval Jordan , Sharavanan Vivek , York Courtney , Zimmer-Faust Amity G. , Langlois Kylie , Steele Joshua A. , Griffith John F. , Whiteson Katrine L. 
Published: August 2022

AbstractMunicipal wastewater provides a representative sample of human fecal waste across a catchment area and contains a wide diversity of microbes. Sequencing wastewater samples provides information about human-associated and medically-important microbial populations, and may be useful to assay disease prevalence and antimicrobial resistance (AMR).Here, we present a study in which we used untargeted metatranscriptomic sequencing on RNA extracted from 275 sewage influent samples obtained from eight wastewater treatment plants (WTPs) representing approximately 16 million people in Southern California between August 2020 – August 2021. We characterized bacterial and viral transcripts, assessed metabolic pathway activity, and identified over 2,000 AMR genes/variants across all samples. Because we did not deplete ribosomal RNA, we have a unique window into AMR carried as ribosomal mutants. We show that AMR diversity varied between WTPs and that the relative abundance of many individual AMR genes/variants increased over time and may be connected to antibiotic use during the COVID-19 pandemic. Similarly, we detected transcripts mapping to human pathogenic bacteria and viruses suggesting RNA sequencing is a powerful tool for wastewater-based epidemiology and that there are geographical signatures to microbial transcription. We captured the transcription of gene pathways common to bacterial cell processes, including central carbon metabolism, nucleotide synthesis/salvage, and amino acid biosynthesis. We also posit that due to the ubiquity of many viruses and bacteria in wastewater, new biological targets for microbial water quality assessment can be developed.To the best of our knowledge, our study provides the most complete longitudinal metatranscriptomic analysis of a large population’s wastewater to date and demonstrates our ability to monitor the presence and activity of microbes in complex samples. By sequencing RNA, we can track the relative abundance of expressed AMR genes/variants and metabolic pathways, increasing our understanding of AMR activity across large human populations and sewer sheds.
The association between experience of COVID-19-related discrimination and psychological distress among healthcare workers for six national medical research centers in Japan
Authors: Shrestha Rachana Manandhar , Inoue Yosuke , Yamamoto Shohei , Fukunaga Ami , Sampei Makiko , Okubo Ryo , Morisaki Naho , Ohmagari Norio , Funaki Takanori , Ishizuka Kazue , Yamaguchi Koushi , Sasaki Yohei , Takeda Kazuyoshi , Miyama Takeshi , Kojima Masayo , Nakagawa Takeshi , Nishimura Kunihiro , Ogata Soshiro , Umezawa Jun , Tanaka Shiori , Inoue Manami , Konishi Maki , Miyo Kengo , Mizoue Tetsuya 
Published: August 2022

AbstractBackgroundDiscrimination has been identified as an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan.MethodsThis cross-sectional study conducted a health survey among 5,703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified job-related factors associated with discrimination.ResultsOf the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (odds ratio [OR]=1.41, 95% confidence interval [CI]=1.28-1.55), had high vs. low viral exposure (OR=2.31, 95%CI=1.81-2.93), and worked for more than 10 hours/day vs. <8 hours/day (OR=1.42, 95%CI=1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The OR (95%CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. The analysis was stratified by sociodemographic and job-related factors and the associations trended in the same direction across subgroups.ConclusionExperience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.