bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental Attitudes Toward Standard Newborn Screening and Newborn Genomic Sequencing: Findings From the BabySeq Study
Authors: Armstrong Brittan , Christensen Kurt D. , Genetti Casie A. , Parad Richard B. , Robinson Jill Oliver , Blout Zawatsky Carrie L. , Zettler Bethany , Beggs Alan H. , Holm Ingrid A. , Green Robert C. , McGuire Amy L. , Smith Hadley Stevens , Pereira Stacey ,   The BabySeq Project Team
Published: April 2022

Introduction: With increasing utility and decreasing cost of genomic sequencing, augmentation of standard newborn screening (NBS) programs with newborn genomic sequencing (nGS) has been proposed. Before nGS can be integrated into newborn screening, parents’ perspectives must be better understood.

Objective: Using data from surveys administered to parents of healthy newborns who were enrolled in the BabySeq Project, a randomized clinical trial of nGS alongside NBS, this paper reports parents’ attitudes regarding population-based NBS and nGS assessed 3 months after results disclosure.

Methods: Parental attitudes regarding whether all newborns should receive, and whether informed consent should be required for, NBS and nGS, as well as whether nGS should be mandated were assessed using 5-point scales from strongly disagree (=1) to strongly agree (=5). Parents’ interest in receiving types of results from nGS was assessed on a 5-point scale from not at all interested (=1) to very interested (=5). Survey responses were analyzed using Fisher’s exact tests, paired t-tests, and repeated measures ANOVA.

Results: At 3 months post-disclosure, 248 parents of 174 healthy newborns submitted a survey. Support for every newborn receiving standard NBS (mean 4.67) was higher than that for every newborn receiving nGS (mean 3.60; p < 0.001). Support for required informed consent for NBS (mean 3.44) was lower than that for nGS (mean 4.27, p < 0.001). Parents’ attitudes toward NBS and nGS were not significantly associated with self-reported political orientation. If hypothetically receiving nGS outside of the BabySeq Project, most parents reported being very interested in receiving information on their baby’s risk of developing a disease in childhood that can be prevented, treated, or cured (86.8%) and their risk of developing a disease during adulthood that can be prevented, treated, or cured (84.6%).

Discussion: Parents’ opinions are crucial to inform design and delivery of public health programs, as the success of the program hinges on parents’ trust and participation. To accommodate parents’ preferences without affecting the current high participation rates in NBS, an optional add-on consent to nGS in addition to NBS may be a feasible approach. Trial Registration ClinicalTrials.gov Identifier: NCT02422511.
CHSY3 can be a Poor Prognostic Biomarker and Mediates Immune Evasion in Stomach Adenocarcinoma
Authors: Li Xinwei , Fan Yongfei , Zhang Yue , Wang Yanyan , Zhao Menglin , Tang Mingyue , Li Huiyuan , Mi Jiaqi , Geng Zhijun , Wang Zishu , Su Fang
Published: April 2022

Background: Chondroitin sulphate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but it has not been reported in tumours. This study explored for the first time the oncological features of CHSY3 in stomach adenocarcinoma (STAD).

Methods: We analysed CHSY3 expression in STAD through the Cancer Genome Atlas (TCGA) database and verified our findings by immunohistochemical staining and Western blot experiments. The prognostic value of CHSY3 in STAD was analysed through the biological aspects of CHSY3 in STAD, such as communal clinical follow-up survival data, methylation sites, tumour immune microenvironment (TIME) and immune cell surface checkpoints. Finally, the immune-evasion potential of CHSY3 in STAD was assessed on the Tumor Immune Dysfunction and Exclusion (TIDE) website and immunohistochemical staining experiment.

Results:CHSY3 overexpression in STAD was associated with a poor prognosis based on immunohistochemical staining and Western blot experiments. Multivariate Cox analysis suggested that CHSY3 could be an independent prognostic risk factor. Pathway enrichment and TIME analysis demonstrated that CHSY3 up-regulated mesenchymal activation and immune activation signals in STAD, while TIDE assessment revealed that the risk of immune evasion was significantly higher in the high CHSY3 expression group than in the low CHSY3 expression group. Risk model scores based on CHSY3-associated immune cell surface checkpoints also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group.

Conclusions: This study analysed CHSY3 from multiple biological perspectives and revealed that CHSY3 can be a biomarker of poor prognosis and mediates the TIME immune-evasion status in STAD.
SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds
Authors: Vadgama Nirmal , Kreymerman Alexander , Campbell Jackie , Shamardina Olga , Brugger Christiane , Research Consortium Genomics England , Deaconescu Alexandra M. , Lee Richard T. , Penkett Christopher J. , Gifford Casey A. , Mercola Mark , Nasir Jamal , Karakikes Ioannis
Published: April 2022

There is considerable variability in the susceptibility and progression for COVID-19 and it appears to be strongly correlated with age, gender, ethnicity and pre-existing health conditions. However, to our knowledge, cohort studies of COVID-19 in clinically vulnerable groups are lacking. Host genetics has also emerged as a major risk factor for COVID-19, and variation in the ACE2 receptor, which facilitates entry of the SARS-CoV-2 virus into the cell, has become a major focus of attention. Thus, we interrogated an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (United Kingdom) to assess the association between variants in the ACE2 locus and COVID-19 risk. We analysed whole-genome sequencing (WGS) data of 1,837 cases who were tested positive for SARS-CoV-2, and 37,207 controls who were not tested, from the UK’s 100,000 Genomes Project (100KGP) for the presence of ACE2 coding variants and extract expression quantitative trait loci (eQTLs). We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = 0.015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = 0.029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing the risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p. H378R, p. Y515N) alter receptor affinity for the viral Spike (S) protein. Variant p. N720D, more prevalent in the European population (p < 0.001), potentially increases viral entry by affecting the ACE2-TMPRSS2 complex. The spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups.
Seroreactivity of the Severe Acute Respiratory Syndrome Coronavirus 2 Recombinant S Protein, Receptor-Binding Domain, and Its Receptor-Binding Motif in COVID-19 Patients and Their Cross-Reactivity With Pre-COVID-19 Samples From Malaria-Endemic Areas
Authors: Traoré Abdouramane , Guindo Merepen A. , Konaté Drissa , Traoré Bourama , Diakité Seidina A. , Kanté Salimata , Dembélé Assitan , Cissé Abdourhamane , Incandela Nathan C. , Kodio Mamoudou , Coulibaly Yaya I. , Faye Ousmane , Kajava Andrey V. , Pratesi Federico , Migliorini Paola , Papini Anna Maria , Pacini Lorenzo , Rovero Paolo , Errante Fosca , Diakité Mahamadou , Arevalo-Herrera Myriam , Herrera Socrates , Corradin Giampietro , Balam Saidou
Published: April 2022

Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroreactivity of antibodies from COVID-19 and pre-COVID-19 samples of individuals in Mali (West Africa). Blood samples from COVID-19 patients (n = 266) at Bamako Dermatology Hospital (HDB) and pre-COVID-19 donors (n = 283) from a previous malaria survey conducted in Dangassa village were tested by ELISA to assess IgG antibodies specific to the full-length spike (S) protein, the receptor-binding domain (RBD), and the receptor-binding motif (RBM436–507). Study participants were categorized by age, gender, treatment duration for COVID-19, and comorbidities. In addition, the cross-seroreactivity of samples from pre-COVID-19, malaria-positive patients against the three antigens was assessed. Recognition of the SARS-CoV-2 proteins by sera from COVID-19 patients was 80.5% for S, 71.1% for RBD, and 31.9% for RBM (p < 0.001). While antibody responses to S and RBD tended to be age-dependent, responses to RBM were not. Responses were not gender-dependent for any of the antigens. Higher antibody levels to S, RBD, and RBM at hospital entry were associated with shorter treatment durations, particularly for RBD (p < 0.01). In contrast, higher body weights negatively influenced the anti-S antibody response, and asthma and diabetes weakened the anti-RBM antibody responses. Although lower, a significant cross-reactive antibody response to S (21.9%), RBD (6.7%), and RBM (8.8%) was detected in the pre-COVID-19 and malaria samples. Cross-reactive antibody responses to RBM were mostly associated (p < 0.01) with the absence of current Plasmodium falciparum infection, warranting further study.
Evidence for a Role of CCR6+ T Cells in Chronic Thromboembolic Pulmonary Hypertension
Authors: van Uden Denise , Koudstaal Thomas , van Hulst Jennifer A. C. , van den Bosch Thierry P. P. , Vink Madelief , Bergen Ingrid M. , Lila Karishma A. , van den Bosch Annemien E. , Bresser Paul , Kool Mirjam , von der Thüsen Jan H. , Hendriks Rudi W. , Boomars Karin A.
Published: April 2022

Introduction

Previous studies have shown an increase of T cells and chemokines in vascular lesions of patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, detailed characterization of these T cells is still lacking, nor have treatment effects been evaluated.

Methods

We included 41 treatment-naive CTEPH patients at diagnosis, 22 patients at 1-year follow-up, and 17 healthy controls (HCs). Peripheral blood T cells were characterized by flow cytometry for subset distribution, cytokine expression and activation marker profile. We used multiplex immunofluorescence to identify CCR6+ T cells in endarterectomy tissue from 25 patients.

Results

At diagnosis, proportions of CCR6+ CD4+ T cells were increased in CTEPH patients compared with HCs. Patients displayed a significantly reduced production capacity of several cytokines including TNFα, IFNγ, GM-CSF and IL-4 in CD4+ T cells, and TNFα and IFNγ in CD8+ T cells. CD4+ and CD8+ T cells showed increased expression of the immune checkpoint protein CTLA4. Multivariate analysis separated CTEPH patients from HCs, based on CCR6 and CTLA4 expression. At 1-year follow-up, proportions of CCR6+CD4+ T cells were further increased, IFNγ and IL-17 production capacity of CD4+ T cells was restored. In nearly all vascular lesions we found substantial numbers of CCR6+ T cells.

Conclusion

The observed increase of CCR6+ T cells and modulation of the IFNγ and IL-17 production capacity of circulating CD4+ T cells at diagnosis and 1-year follow-up – together with the presence of CCR6+ T cells in vascular lesions - support the involvement of the Th17-associated CCR6+ T cell subset in CTEPH.
Performance of Seismic Observation by Distributed Acoustic Sensing Technology Using a Seafloor Cable Off Sanriku, Japan
Authors: Shinohara Masanao , Yamada Tomoaki , Akuhara Takeshi , Mochizuki Kimihiro , Sakai Shin’ichi
Published: April 2022

Recently, the distributed acoustic sensing (DAS) measurement, which utilizes an optical fiber itself as a sensor, becomes popular for various fields and is being applied to seismic observations. The shortest spatial sampling of DAS observations reaches a few meters, and the total measurement distance becomes greater than 50 km. A high temporal sampling rate is achieved. Due to these characteristics, a DAS measurement allows for a dense seismic observation as a linear array. Applying a DAS measurement to the seafloor cable is advantageous because the quantity of data can be significantly increased in a marine area. A seafloor seismic tsunami observation cable system using an optical fiber for data transmission was deployed off Sanriku by the Earthquake Research Institute, the University of Tokyo in 1996. This seafloor cable observation system has spare fibers for extension. Beginning in February 2019, we made several DAS observations using the spare fibers of the seafloor system. Consequently, many earthquakes were recorded. Small earthquakes with a magnitude of 1.8 occurring near the cable system were recorded by the DAS system. The arrivals of P- and S-waves of the earthquake with a magnitude of 3 were clearly seen using the phase data from the DAS measurement. In addition, a teleseismic event with an epicentral distance of approximately 2,300 km and a magnitude of 6.6 was clearly observed. Because there are conventional seismometers in the Sanriku cable system, we compared records from the DAS measurement with those from the seismometer. The DAS records and the data by the seismometer showed a high coherency. The noise levels of the DAS measurement were evaluated, and there was little temporal variation of the noise levels. A spatial variation of ambient seismic noises was revealed using a spatially high-density observation with a long distance. In November 2020, a seismic survey using the DAS system and airguns was carried out, and the DAS system clearly recorded signals from the airguns. We also compared these data from the DAS system with that of the seismometer. Both records had the same characteristics, although P-wave arrivals on the DAS records have smaller amplitude.
Blue Carbon Storage in a Northern Temperate Estuary Subject to Habitat Loss and Chronic Habitat Disturbance: Cowichan Estuary, British Columbia, Canada
Authors: Douglas Tristan J. , Schuerholz Goetz , Juniper S. Kim
Published: April 2022

Vegetated coastal ecosystems can contribute greatly to long-term carbon sequestration and greenhouse gas emission mitigation, providing a strong argument for their protection and restoration. We investigated carbon sequestration in the Cowichan Estuary, a temperate estuary on Vancouver Island, Canada, in relation to habitat type (salt marsh, eelgrass, mudflats, and oyster shell beds) and habitat degradation. Stored organic carbon and inorganic carbon were quantified in the top 20 cm of sediment as well as in eelgrass and salt marsh vegetation. Sedimentation and carbon sequestration rates were quantified by 210Pb radiometric dating, and organic matter sources and quality were assessed by δ13C, C:N ratios and photopigment content. We also examined the potential impact of habitat disturbance by industrial activity (log booms) on the estuary’s carbon storage capacity. The salt marsh was the most important carbon reservoir, with a mean sediment organic carbon stock of 58.78 ± 19.30 Mg C ha-1. Sediment organic carbon stocks in the upper mudflats, lower mudflats, eelgrass meadow, and oyster shell beds were 19.30 ± 3.58, 17.33 ± 3.17, 18.26 ± 0.86 and 9.43 ± 1.50 Mg C ha-1, respectively. Carbon accumulation rates in the salt marsh and eelgrass meadows were 68.21 ± 21 and 38 ± 26 g C m-2 yr-1, whereas 210Pb profiles indicated that mudflat sediments were subject to erosion and/or mixing. While eelgrass was absent from the log boom area, likely due to disturbance, sediments there had similar carbon sequestration and bulk properties to adjacent mudflats. Carbon stocks in the eelgrass meadow were similar to those of the mudflats and consistent with the relatively low values reported for other temperate Zostera marina meadows, compared with tropical eelgrass meadows. Stable isotope evidence was suggestive of substantial outwelling and/or decomposition of eelgrass vegetation. Finally, we compared the carbon sequestration potential of the estuary to selected sources and sinks of CO2 in the surrounding region. We estimated that annual carbon sequestration in the estuary offsets approximately twice the greenhouse gas emission increases attributable to local population growth, and is equivalent to approximately twice that of a 20-year-old stand forest.
Distribution of the Mesozooplankton Community in the Western Ross Sea Region Marine Protected Area During Late Summer Bloom
Authors: Kim Sung Hoon , Kim Bo Kyung , Lee Boyeon , Son Wuju , Jo Naeun , Lee Junbeom , Lee Sang Heon , Ha Sun-Yong , Kim Jeong-Hoon , La Hyoung Sul
Published: April 2022

The spatio-temporal distributions of the epipelagic mesozooplankton community in the western Ross Sea region marine protected area (RSR MPA) were investigated. Mesozooplankton surveys were conducted in February 2018, January 2019, and March 2020 from an approximate depth of 200 m to address the essential environmental factors influencing the mesozooplankton community structure. Our results showed that the mesozooplankton community of the western RSR MPA could be affected by the various ecological factors, depending on their temporal and spatial variations. The community structure in 2018 was distinguished by its chlorophyll-a (Chl-a) concentration during the summer bloom phase in the late summer. Taxa observed in 2019 were divided into four significantly different groups according to the body size of the community composition. This differentiation could be derived from predation pressure, inducing a trophic cascade. Taxa in the 2020 samples were separated into five different groups based on temperature; during the 2020 survey, the water temperature was low and sea ice covered the whole continental shelf in the Ross Sea. Additionally, comparing the results from the three interannual surveys, although the communities clustered according to the survey period, the continental shelf groups were quite dissimilar despite overlapping geographically. Taken all together, the mesozooplankton community of the western RSR MPA changed according to changes in several ecological factors, such as temperature, Chl-a concentration, and predation pressure. The occurrence of summer blooms and the decline in water temperature mainly regulated the mesozooplankton community structure in the late summer.
Feeding Strategies of Mangrove Leaf-Eating Crabs for Meeting Their Nitrogen Needs on a Low-Nutrient Diet
Authors: Gao Xueqin , Lee Shing Yip
Published: April 2022

Sesarmid crabs play an important role in mangrove biogeochemical processes due to their leaf-eating and burrowing activities. How leaf-eating mangrove crabs meet their nitrogen (N) needs remains a puzzle, as N-poor leaf litter (<1% dry weight) cannot support the growth of most macrofauna. Several strategies for overcoming this challenge have been proposed, but the actual mechanisms remain unknown. We identified two categories of leaf-eating crabs according to their feeding habits (1): species active outside their burrows during low tide - we hypothesize that they meet their N needs through consuming the microphytobenthos (MPB) (hypothesis H1); and (2) species spending most of their time inside burrows - we hypothesize that they meet their N needs through N-fixation by associated microbes (H2). To test H1, we conducted a series of feeding experiments on the sesarmid crab Parasesarma affine (model species for category 1) with 13C- and 15N-enriched MPB and mangrove leaves. P. affine relied mainly on mangrove leaves as their C source and MPB as their N source, supporting H1. Two feeding experiments on Neosarmatium smithi (model species for category 2) showed that N limitation could be ameliorated by selecting seasonally available higher-quality food items such as floral parts, or by supplements from the associated nitrogen-fixing bacteria, as identified by genomic analysis. The strategy by which leaf-eating crabs meet their N needs may make significant contribution both to the growth of crabs and to their ecosystem functions of regulating the cycling of significant nutrient elements. The stoichiometric regulations by leaf-eating crabs to meet their N needs, such as food selection, can enhance trophic efficiency and nutrient transfer rate at the community level and ultimately increase nutrient turnover rate at the ecosystem level.
Biopolymer Nanocomposites for Sustainable UV Protective Packaging
Authors: Gore Anil H. , Prajapat Amrutlal L.
Published: April 2022

The development of green, eco-friendly and sustainable packaging materials is a major challenge in the field of nanoscience and nanotechnology. Advancements in the designing biopolymeric nanocomposites for packaging applications have been established by considering features like biodegradability, environmental friendliness, mechanical properties, cost, safety, etc. Other properties such as thickness, weight, transparency, practicability, recyclability, antimicrobial, porosity, leaching effect, light protective capability, etc. need to be considered during the fabrication of next-generation packing materials for multifaceted applications. Of these, the ultraviolet (UV) protective properties of the designed nanocomposites for sustainable packaging applications are extremely important. The UV protective properties of the packaging materials can be modulated by adding a minute amount of biocompatible nanomaterials with maximum absorption properties in the UV region (200–400 nm). UV light absorption is very important to avoid loss or changes in intrinsic chemical, physical, and biological properties/content of foods, pharmaceuticals, beverages, and so forth during storage and transportation. In the current review, we highlight the principle of UV light protection, the selection of nanomaterials, and the design of nanocomposite films, including the properties and applications of biopolymeric nanocomposite materials for UV protective sustainable packaging. Lastly, the current challenges and prospects of sustainable UV protective packaging are also discussed to provide insights into the future of next-generation packaging technologies.
Optimal Data-Generation Strategy for Machine Learning Yield Functions in Anisotropic Plasticity
Authors: Shoghi Ronak , Hartmaier Alexander
Published: April 2022

Trained machine learning (ML) algorithms can serve as numerically efficient surrogate models of sophisticated but numerically expensive constitutive models of material behavior. In the field of plasticity, ML yield functions have been proposed that serve as the basis of a constitutive model for plastic material behavior. If the training data for such ML flow rules is gained by micromechanical models, the training procedure can be considered as a homogenization method that captures essential information of microstructure-property relationships of a given material. However, generating training data with micromechanical methods, as for example, the crystal plasticity finite element method, is a numerically challenging task. Hence, in this work, it is investigated how an optimal data-generation strategy for the training of a ML model can be established that produces reliable and accurate ML yield functions with the least possible effort. It is shown that even for materials with a significant plastic anisotropy, as polycrystals with a pronounced Goss texture, 300 data points representing the yield locus of the material in stress space, are sufficient to train the ML yield function successfully. Furthermore, it is demonstrated how data-oriented flow rules can be used in standard finite element analysis.
Investigation of Surface Charge at the Mineral/Brine Interface: Implications for Wettability Alteration
Authors: Mohammed Isah , Al Shehri Dhafer , Mahmoud Mohamed , Kamal Muhammad Shahzad , Arif Muhammad , Alade Olalekan Saheed , Patil Shirish
Published: April 2022

The reservoir rock ismade up of differentminerals which contribute to the overall formation wettability. These minerals in their natural state differ in chemistry and structure, and thus behave differently in an environment of varying composition and salinity. These have direct implications for enhanced oil recovery due to water flooding, or wettability alteration due to long-term exposure to brine. With the reservoir rock being a complex system of multiple minerals, the control of wettability alterations becomes difficult to manage. One of the dominant mechanisms responsible for wettability alteration is the mineral surface charge, which is dependent on pH, and fluid composition (salt type and salinity). For the first time, the surface charge development of barite, dolomite, and feldspar minerals in their native reservoir environments (accounting for the formation brine complexity) is presented. Also, the effect of oilfield operations (induced pH change) on minerals’ surface charge development is studied. This was achieved by using the zeta potential measurements. The zeta potential results show that barite and dolomite minerals possess positively charge surfaces in formation water and seawater, with feldspar having a near-zero surface charge. Furthermore, the surface charge development is controlled by the H+/OH− (pH), electrical double-layer effect, as well as ion adsorption on the mineral’s surfaces. These findings provide key insights into the role of fluid environment (pH, composition) and oilfield operations on mineral surface charge development. In addition, the results show that careful tuning of pH with seawater injection could serve as an operational strategy to control the mineral surface charge. This is important as negatively charged surfaces negate wettability alteration due to polar crude oil components. Also, the design of an ion-engineered fluid to control the surface charge of minerals was implemented, and the results show that reduction in the Ca2+ concentration holds the key to the surface charge modifications. Surface charge modifications as evidenced in this study play a critical role in the control of wettability alteration to enhance production.
On the Development of Efficient Solvers for Real-World Coupled Hydromechanical Simulations
Authors: Ferronato Massimiliano , Franceschini Andrea , Frigo Matteo
Published: April 2022

Linear solvers usually are the most time- and memory-demanding part of a full coupled hydromechanical simulation. The typical block structure of the linearized systems arising from a fully-implicit solution approach requires the development of specialized algorithms, ensuring both robustness and computational efficiency. In particular, the design of the preconditioner to accelerate iterative methods based on Krylov subspaces is key for the overall model effectiveness. This work introduces a unifying framework for the development of preconditioning techniques in multi-physics problems, and specifically in coupled poromechanics, with the aim to provide existing methods with a novel interpretation. Three approaches, namely explicit, implicit and reverse, are considered and compared in real-world challenging benchmarks, identifying merits and drawbacks of each strategy. The proposed framework can open the way to a systematic comparison of available preconditioning tools for coupled poromechanics and help generalize the existing methods for the introduction of additional physical processes in the simulation.
A Mathematical Model of a Valve-Controlled Bioreactor for Platelet Production
Authors: Saville Helen M. , Howard Daniel , Ghevaert Cédric , Best Serena M. , Cameron Ruth E. , Oliver James M. , Waters Sarah L.
Published: April 2022

As blood donor numbers decrease, while demand for platelets increases, hospitals worldwide are becoming increasingly vulnerable to critical platelet shortages. Alternative methods of supplying platelets are therefore required. One approach is to engineer platelets in vitro in a bioreactor. To characterise such a system, we develop a mathematical model of a novel platelet bioreactor described in Shepherd et al. (Biomaterials, 2018, 182, 135–144). The bioreactor consists of upper and lower tube systems, with a cell-seeded porous collagen scaffold situated between them. Flow through the system is driven by gravity, and controlled by valves on each of the inlets and outlets. The bioreactor is long relative to its width, a feature which we exploit to derive a lubrication reduction of the Navier-Stokes equations for flow in the tube systems, coupled to Darcy flow through the porous scaffold. Flow in the tube systems and scaffold are coupled to form a network model for the bioreactor flow. We characterise the effect of geometrical parameters and valve configuration and synchronisation, on the fluxes through the bioreactor and shear stress experienced by cells in the scaffold. The simplicity of the model means that parameter sweeps take only seconds or minutes to perform, making the model a convenient tool for future bioreactor design optimisation.
A Fractional Time-Derivative Model for Severe Wear: Hypothesis and Implications
Authors: Argatov Ivan
Published: April 2022

Based on the example of wear of polymers, which exhibit a power-law time variation of the wear loss under constant loading conditions, a fractional time-derivative wear equation has been introduced. The wear contact problem with a fixed contact zone is solved using the known method of separation of spatial and time variables. It is shown that during the wear process, the contact pressure approaches a uniform distribution over the contact area, which is termed as a quasi-steady-state solution, since the mean volumetric wear rate does not tend to become constant. It is of interest that the contact pressure variation displays a decaying oscillatory nature in the case of severe wear, when the mean volumetric wear rate increases with time.
Frequently Transmission and Close Relationship Among Immigrants in the China–Myanmar Border Region Indicated by Molecular Transmission Analysis From a Cross-Sectional Data
Authors: Hu Zhili , Liu Yingjie , Wang Jibao , Meng Zhefeng , Leuba Sequoia I. , Wei Jie , Duan Xing , Chu Zhenxing , Chen Min , Shang Hong , Xu Junjie
Published: April 2022

Background

Accurate identification of molecular transmission clusters (MTCs) and understanding the dynamics of human immunodeficiency virus (HIV) transmission are necessary to develop targeted interventions to prevent HIV transmission. We evaluated the characteristics of antiretroviral therapy-naïve individuals who belonged to HIV-1 MTCs in the China–Myanmar border region to inform targeted effective HIV intervention.

Methods

Phylogenetic analyses were undertaken on HIV-1 pol sequences to characterize subtypes or circulating recombinant forms and identify MTCs. MTCs were defined as those with 2 or more sequences having bootstrap support > 80% and a pairwise gene distance less than or equal to 0.03. Factors correlated with MTCs were evaluated using logistic regression analysis. The chi-square test was used to compare differences between Chinese and Burmese participants belonging to MTCs.

Results

A total of 900 people had their pol gene successfully sequenced. Twenty-one MTCs were identified and included 110 individuals (12.2%). Individuals in MTCs were more likely to be Burmese [aOR = 2.24 (95% CI: 1.33, 3.79), P = 0.003], be younger [aOR = 0.34 (95% CI: 0.20, 0.58), P < 0.001 for age 26–50 vs. 25 years or younger], have a lower CD4 T cell count [aOR = 2.86 (95% CI: 1.34, 6.11), P = 0.007 for < 200 vs. 350 or greater], and have subtypes CRF07_BC or C [CRF07_BC: aOR = 7.88 (95% CI: 3.55, 17.52), P < 0.001; C: aOR = 2.38 (95% CI: 1.23, 4.62), P = 0.010 compared to CRF01_AE]. In MTCs, Burmese were younger (89.7 vs. 57.7% for age 25 years or younger), had a lower education level (41.0 vs. 8.5% for illiterate), were more likely to be infected through injection drug use (35.9 vs. 12.7%), and had a higher proportion of subtype BC (33.3 vs. 15.5%) and CRF01_AE (20.5 vs. 8.5%) compared to Chinese (P < 0.05 for all).

Conclusion

Burmese participants were more likely to belong to MTCs, and most MTCs had both Burmese and Chinese participants. These data highlight the bidirectional transmission of HIV-1 frequently transmission and close relationship among immigrants in the China–Myanmar border region. Local health departments should pay more attention to HIV screening and intervention to immigrants Burmese with the characteristics of younger age, having lower CD4 T cell count and infected with HIV subtypes CRF07_ BC or C.
The Incidence of Contrast-Induced Nephropathy and the Need of Dialysis in Patients Receiving Angiography: A Systematic Review and Meta-Analysis
Authors: Wu Mei-Yi , Lo Wei-Cheng , Wu Yun-Chun , Lin Tsu-Chen , Lin Chun-Hung , Wu Mai-Szu , Tu Yu-Kang
Published: April 2022

Objectives

The risk of dialysis following contrast exposure is unclear. We aimed to examine the overall risk of contrast induced nephropathy and the need of dialysis based on a systematic review with random-effects meta-analysis.

Methods

We searched the electronic database including PubMed, Medline, Embase, and Cochrane Library from inception to 31 October, 2020 with predetermined search term to identify relevant studies. Observational studies investigating the association between contrast induced nephropathy after angiography and the need of dialysis were included, and summary risks were estimated. Two independent reviewers extracted the data, followed with random effects model to calculate the overall pooled incidence of contrast induced nephropathy and the need of dialysis after angiography. Subgroup-analysis and meta-regression were performed to assess heterogeneity of incidence across studies.

Results

Of 2,243 identified articles, 259 met our inclusion criteria were included in the meta-analysis after screening. Pooled effect estimates had the following summary incidence proportion for contrast induced nephropathy after angiography: 9.06% (95% CI: 8.53–9.58%; derived from 120 studies) and 0.52% (95% CI: 0.37–0.70%; derived from 110 studies) for the need of dialysis, respectively. The stratified summary incidence proportion of contrast induced nephropathy after contrast administration via intra-arterial route was 9.60% (95% CI: 9.0–10.2%; derived from 106 studies) and was 0.6% (95% CI: 0.40–0.80%; derived from 100 studies) for the need of dialysis, respectively. Our meta-regressions found that the amount of contrast medium exposure was associated with contrast-induced nephropathy.

Conclusion

The potential risk of dialysis needs to be communicated to patients undergoing procedures requiring contrast, especially via intra-arterial exposure.

Systematic Review Registration

[https://reurl.cc/8Wrlry], identifier [CRD42020170702].
Treatment Strategies in Emergency Endoscopy for Acute Esophageal Variceal Bleeding (CHESS1905): A Nationwide Cohort Study
Authors: Huang Yifei , Zhang Wenhui , Xiang Huiling , Liu Yanna , Yuan Lili , Zhang Liyao , Hu Shengjuan , Xia Dongli , Li Jia , Gao Min , Wang Xing , Qi Xingsi , Peng Lijun , Song Ying , Zhou Xiqiao , Zeng Jing , Tan Xiaoyan , Deng Mingming , Fang Haiming , Qi Shenglin , He Song , He Yongfeng , Ye Bin , Wu Wei , Dang Tong , Shao Jiangbo , Wei Wei , Hu Jianping , Yong Xin , He Chaohui , Bao Jinlun , Zhang Yuening , Zhang Guo , Ji Rui , Bo Yang , Yan Wei , Li Hongjiang , Wang Yanling , Li Mengmeng , Wang Fengmei , Lian Jia , Liu Chang’en , Cao Ping , Liu Zhenbei , Liu Aimin , Zhao Lili , Li Shuang , Wu Yunhai , Gu Ye , Wang Yan , Fang Yanfei , Jiang Pan , Wu Bin , Liu Chuan , Qi Xiaolong
Published: April 2022

Background and Aims

Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB.

Methods

Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed.

Results

A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively).

Conclusion

The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.
Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies
Authors: Ta Tram M. , Malik Sajjaf , Anderson Elizabeth M. , Jones Amber D. , Perchik Jocelyn , Freylikh Maryann , Sardo Luca , Klase Zackary A. , Izumi Taisuke
Published: April 2022

Although HIV-1 replication can be efficiently suppressed to undetectable levels in peripheral blood by combination antiretroviral therapy (cART), lifelong medication is still required in people living with HIV (PLWH). Life expectancies have been extended by cART, but age-related comorbidities have increased which are associated with heavy physiological and economic burdens on PLWH. The obstacle to a functional HIV cure can be ascribed to the formation of latent reservoir establishment at the time of acute infection that persists during cART. Recent studies suggest that some HIV reservoirs are established in the early acute stages of HIV infection within multiple immune cells that are gradually shaped by various host and viral mechanisms and may undergo clonal expansion. Early cART initiation has been shown to reduce the reservoir size in HIV-infected individuals. Memory CD4+ T cell subsets are regarded as the predominant cellular compartment of the HIV reservoir, but monocytes and derivative macrophages or dendritic cells also play a role in the persistent virus infection. HIV latency is regulated at multiple molecular levels in transcriptional and post-transcriptional processes. Epigenetic regulation of the proviral promoter can profoundly regulate the viral transcription. In addition, transcriptional elongation, RNA splicing, and nuclear export pathways are also involved in maintaining HIV latency. Although most proviruses contain large internal deletions, some defective proviruses may induce immune activation by expressing viral proteins or producing replication-defective viral-like particles. In this review article, we discuss the state of the art on mechanisms of virus persistence in the periphery and tissue and summarize interdisciplinary approaches toward a functional HIV cure, including novel capabilities and strategies to measure and eliminate the infected reservoirs and induce immune control.
Combination of Genome-Scale Models and Bioreactor Dynamics to Optimize the Production of Commodity Chemicals
Authors: Lázaro Jorge , Jansen Giorgio , Yang Yiheng , Torres-Acosta Mario A. , Lye Gary , Oliver Stephen G. , Júlvez Jorge
Published: April 2022

The current production of a number of commodity chemicals relies on the exploitation of fossil fuels and hence has an irreversible impact on the environment. Biotechnological processes offer an attractive alternative by enabling the manufacturing of chemicals by genetically modified microorganisms. However, this alternative approach poses some important technical challenges that must be tackled to make it competitive. On the one hand, the design of biotechnological processes is based on trial-and-error approaches, which are not only costly in terms of time and money, but also result in suboptimal designs. On the other hand, the manufacturing of chemicals by biological processes is almost exclusively carried out by batch or fed-batch cultures. Given that batch cultures are expensive and not easy to scale, technical means must be developed to make continuous cultures feasible and efficient. In order to address these challenges, we have developed a mathematical model able to integrate in a single model both the genome-scale metabolic model for the organism synthesizing the chemical of interest and the dynamics of the bioreactor in which the organism is cultured. Such a model is based on the use of Flexible Nets, a modeling formalism for dynamical systems. The integration of a microscopic (organism) and a macroscopic (bioreactor) model in a single net provides an overall view of the whole system and opens the door to global optimizations. As a case study, the production of citramalate with respect to the substrate consumed by E. coli is modeled, simulated and optimized in order to find the maximum productivity in a steady-state continuous culture. The predicted computational results were consistent with the wet lab experiments.
Profiling the Research Landscape on Cognitive Aging: A Bibliometric Analysis and Network Visualization
Authors: Othman Zahiruddin , Abdul Halim Ahmad Shahril , Azman Khairunnuur Fairuz , Ahmad Asma Hayati , Zakaria Rahimah , Sirajudeen Kuttulebbai Nainamohamed Salam , Wijaya Adi , Ahmi Aidi
Published: April 2022

Objectives

This study aimed to profile the cognitive aging research landscape from 1956 to 2021.

Methods

A total of 3,779 documents were retrieved from the Scopus database for the bibliometric analysis and network visualization. By comparing each keyword’s overall connection strength (centrality), frequency (density), and average year of publication (novelty) to the calculated median values acquired from the overlay view of the VOSviewer map, the enhanced strategic diagrams (ESDs) were constructed.

Results

The findings showed an increasing trend in the number of publications. The United States leads the contributing countries in cognitive aging research. The scientific productivity pattern obeyed Lotka’s law. The most productive researcher was Deary, I. J., with the highest number of publications. The collaborative index showed an increasing trend from 1980 onwards. Frontiers in Aging Neuroscience is the most prestigious journal in the field of cognitive aging research. In Bradford core journals zone 1, the top 10 core journals of cognitive aging research provided more than half of the total articles (697, or 55.36 percent).

Conclusions

For the next decades, the trending topics in cognitive aging research include neuropsychological assessment, functional connectivity, human immunodeficiency virus (HIV), decision-making, gender, compensation, default mode network, learning and memory, brain-derived neurotrophic factor (BDNF), obesity, D-galactose, epigenetics, frailty, mortality, mini-mental state examination (MMSE), anxiety, and gait speed.
Initial Variability and Time-Dependent Changes of Neuronal Response Features Are Cell-Type-Specific
Authors: Scherer Jens-Steffen , Riedesel Oda E. , Arkhypchuk Ihor , Meiser Sonja , Kretzberg Jutta
Published: April 2022

Different cell types are commonly defined by their distinct response features. But several studies proved substantial variability between cells of the same type, suggesting rather the appraisal of response feature distributions than a limitation to “typical” responses. Moreover, there is growing evidence that time-dependent changes of response features contribute to robust and functional network output in many neuronal systems. The individually characterized Touch (T), Pressure (P), and Retzius (Rz) cells in the medicinal leech allow for a rigid analysis of response features, elucidating differences between and variability within cell types, as well as their changes over time. The initial responses of T and P cells to somatic current injection cover a wide range of spike counts, and their first spike is generated with a high temporal precision after a short latency. In contrast, all Rz cells elicit very similar low spike counts with variable, long latencies. During prolonged electrical stimulation the resting membrane potential of all three cell types hyperpolarizes. At the same time, Rz cells reduce their spiking activity as expected for a departure from the spike threshold. In contrast, both mechanoreceptor types increase their spike counts during repeated stimulation, consistent with previous findings in T cells. A control experiment reveals that neither a massive current stimulation nor the hyperpolarization of the membrane potential is necessary for the mechanoreceptors’ increase in excitability over time. These findings challenge the previously proposed involvement of slow K+-channels in the time-dependent activity changes. We also find no indication for a run-down of HCN channels over time, and a rigid statistical analysis contradicts several potential experimental confounders as the basis of the observed variability. We conclude that the time-dependent change in excitability of T and P cells could indicate a cell-type-specific shift between different spiking regimes, which also could explain the high variability in the initial responses. The underlying mechanism needs to be further investigated in more naturalistic experimental situations to disentangle the effects of varying membrane properties versus network interactions. They will show if variability in individual response features serves as flexible adaptation to behavioral contexts rather than just “randomness”.
Superior Longitudinal Fasciculus: A Review of the Anatomical Descriptions With Functional Correlates
Authors: Janelle Felix , Iorio-Morin Christian , D'amour Sabrina , Fortin David
Published: April 2022

The superior longitudinal fasciculus (SLF) is part of the longitudinal association fiber system, which lays connections between the frontal lobe and other areas of the ipsilateral hemisphere. As a dominant association fiber bundle, it should correspond to a well-defined structure with a clear anatomical definition. However, this is not the case, and a lot of confusion and overlap surrounds this entity. In this review/opinion study, we survey relevant current literature on the topic and try to clarify the definition of SLF in each hemisphere. After a comparison of postmortem dissections and data obtained from diffusion MRI studies, we discuss the specifics of this bundle regarding its anatomical landmarks, differences in lateralization, as well as individual variability. We also discuss the confusion regarding the arcuate fasciculus in relation to the SLF. Finally, we recommend a nomenclature based on the findings exposed in this review and finalize with a discussion on relevant functional correlates of the structure.