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Background and Aims: Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC. Methods: Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI). Results: 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2–0.5) in AHP, 0.4 (0.2–0.6) in AIP, 0.3 (0–0.4) in VP, and 0.2 (0.1–0.6) in HCP. The risk was 0.4 (0.2–0.6) in females, 0.3 (0.1–0.5) in males, 0.9 (0.1–1.7) in symptomatic, and 0.5 (0–1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis. Conclusions: The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP. [ABSTRACT FROM AUTHOR]

Despite substantial neuroscience research in the last decade revealing the claustrum's prominent role in mammalian forebrain organization, as evidenced by its extraordinarily widespread connectivity pattern, claustrum studies in humans are rare. This is particularly true for studies focusing on claustrum connections. Two primary reasons may account for this situation: First, the intricate anatomy of the human claustrum located between the external and extreme capsule hinders straightforward and reliable structural delineation. In addition, the few studies that used diffusion‐weighted‐imaging (DWI)‐based tractography could not clarify whether in vivo tractography consistently and reliably identifies claustrum connections in humans across different subjects, cohorts, imaging methods, and connectivity metrics. To address these issues, we combined a recently developed deep‐learning‐based claustrum segmentation tool with DWI‐based tractography in two large adult cohorts: 81 healthy young adults from the human connectome project and 81 further healthy young participants from the Bavarian longitudinal study. Tracts between the claustrum and 13 cortical and 9 subcortical regions were reconstructed in each subject using probabilistic tractography. Probabilistic group average maps and different connectivity metrics were generated to assess the claustrum's connectivity profile as well as consistency and replicability of tractography. We found, across individuals, cohorts, DWI‐protocols, and measures, consistent and replicable cortical and subcortical ipsi‐ and contralateral claustrum connections. This result demonstrates robust in vivo tractography of claustrum connections in humans, providing a base for further examinations of claustrum connectivity in health and disease. [ABSTRACT FROM AUTHOR]

In 5G networks and beyond, managing handovers (HOs) becomes complex because of frequent user transitions through small coverage areas. The abundance of small cells (SCs) also complicates HO decisions, potentially leading to inefficient resource utilization. To optimize this process, we propose an intelligent algorithm based on a method that utilizes a fuzzy logic controller (FLC), leveraging prior expertise to dynamically adjust the time-to-trigger (TTT), and handover margin (HOM) in a 5G ultra-dense SC heterogeneous network (HetNet). FLC refines TTT based on the user's velocity to improve the response to movement. Simultaneously, it adapts HOM by considering inputs such as the reference signal received power (RSRP), user equipment (UE) speed, and cell load. The proposed approach enhances HO decisions, thereby improving the overall system performance. Evaluation using metrics such as handover rate (HOR), handover failure (HOF), radio link failure (RLF), and handover ping-pong (HOPP) demonstrate the superiority of the proposed algorithm over existing approaches. [ABSTRACT FROM AUTHOR]

Background: Anti‐obesity medications (AOMs) may provide a viable option for obesity management. However, little is known about the use of AOMs in persons with SCI/D. Objective: Describe health care providers' (HCPs) views about barriers to AOM use in persons living with SCI/D. Methods: Descriptive qualitative design using in‐depth interviews Descriptive statistics were used to calculate demographic and employment characteristics. Interviews were audio‐recorded and transcribed verbatim. Transcripts were coded and analyzed using Braun and Clarke's (2006) six thematic analysis phases. Results: HCPs (n = 12) were from 11 different nationwide facilities. Most HCPs were male (75%), a large majority were white (67%), and most were 26–49 years of age. Participants were dietitians (75%), physicians (17%), and psychologists (8%). HCPs ranged from 1.5 to 15 years of providing SCI/D care. HCPs described four main thematic barriers to AOM use in persons with SCI/D: (1) AOM side effects that are especially concerning in persons with SCI/D; (2) AOMs contribute to poor eating habits; (3) availability, accessibility, and administration; and (4) lack of evidence, clinical agreement, and knowledge about AOM use in the SCI/D population. Conclusions: There are several potential barriers to AOM use in the SCI/D population. Barriers include AOM side effects which may cause or exacerbate conditions that are already concerns in persons with SCI/D, such as bowel and skin problems, and muscle loss. SCI/D HCPs reported a lack of evidence about AOM use in persons with SCI/D, but interest in obtaining more knowledge. [ABSTRACT FROM AUTHOR]

Hexagonal close-packed (HCP) metals, particularly Zirconium (Zr), Titanium (Ti), and Magnesium (Mg) alloys, have attracted significant attention due to their unique properties and wide-ranging applications in the aerospace, biomedical, and energy industries. This review paper provides a comprehensive analysis of the microstructural and textural evolution in these HCP materials under various conditions, including rolling, extrusion, drawing, and annealing. The focus of the present work lies on the deformed microstructure and texture development in HCP metals, thus elucidating the fundamental mechanisms that govern their response to mechanical stress. The interaction between dislocation movements, twinning, and slip systems is discussed in detail, illustrating how these factors contribute to the anisotropic behavior characteristic of low-symmetry HCP structures. Unlike high-symmetry metals, deformation in Zr alloys depends on the activation of various slips and twin deformation modes, which are sensitive to crystallographic orientation and strain. Like Zr, Ti alloys present a more complex deformation behavior, heavily influenced by their crystallographic orientation. The most common deformation textures in Ti alloys include split-transverse direction (split-TD), split-rolling direction (split-RD), and normal direction (ND) symmetric basal fiber textures. These textures emerge due to the activation of multiple slip systems and twinning, which are dependent on external factors such as temperature, strain rate, and alloy composition. For Mg alloys, the poor formability and brittleness associated with the dominance of the basal slip system under ambient conditions is a critical material development challenge. The activation of non-basal slip systems introduces complexities in controlling texture and microstructure. However, their activation is crucial for optimizing mechanical properties such as strength and fatigue resistance. The tendency for twinning in Mg alloys further complicates their deformation behavior, leading to challenges in ensuring uniform mechanical performance. Modifying the alloy composition, grain size, and texture can additionally influence the activation of these deformation mechanisms. This review further explores the roles of dynamic recrystallization and grain growth in tailoring mechanical properties, with a particular focus on microstructure and texture evolution during annealing. Through this detailed review, we aim to present a thorough understanding of the microstructural and textural evolution in HCP materials, thereby guiding future research and industrial applications. [ABSTRACT FROM AUTHOR]

Polysorbates, in particular polysorbate (PS) 20 and 80, are the most commonly used surfactants for stabilising biotherapeutics produced by biotechnological processes. PSs are derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids of varying chain length and degree of saturation. In the past, these surfactants have been reported to have specific liabilities. Chemical (oxidations and hydrolyses) and enzymatic degradations have been reported to affect the stability of PS in drug products. Specifically, the presence of trace amounts (sub-ppm) of certain host cell proteins (HCPs) can induce enzymatic PS degradation, which can lead to the release of free fatty acids during storage over time. Enzymatic polysorbate degradation may impair the functionality of the surfactant in stabilising therapeutic proteins, leading to the formation of visible and/or sub-visible particles in biopharmaceutical drug products. This review summarises the enzymes currently known to be involved in the degradation of polysorbate in mammalian biotechnological processes for therapeutic proteins. In recent years, advanced analytical methods have been developed to qualify and quantify the PS-degrading enzymes. Most of these assays are based on mass spectrometry with a preceding HCP enrichment approach. Efforts were made to measure the enzyme activity and correlate it with observed PS degradation. The impact on drug product quality attributes, including fatty acid solubility and phase separation, up to the formation of visible particles, and the potential induction of protein and protein/fatty acid mixed particles as well as the sensitivity of specific PS quality towards enzymatic degradation, was considered. Various drug substance (DS) mitigation strategies related to the occurrence of PS degrading enzymes are discussed as amongst them the generation of stable HCP knockout cell lines, which are also carefully analysed. The underlying opinion article reflects the undergoing discussions related to PS degrading enzymes and focusses on (i) impact on drug product, (ii) analytics for identification/quantification (characterisation) of the PS degrading enzymes, (iii) enzyme activity (iv) currently identified enzymes, and (v) potential mitigation strategies to avoid enzymatic PS degradation during DS manufacturing.

This paper aims to apply the halal value chain to Tanah Liek Batik textiles to become halal batik products, using a framework designed to analyze the halal value chain. The method used in dealing with this problem is to apply HCCP (Halal Critical Control Point) to the company's activity value chain to become a halal value chain. The initial data used is a flow diagram of the production process of four types of Tanah Liek Batik products: Tanah Liek dyed batik, chemically dyed batik, stamped batik with soil-like dye, and chemically dyed batik. Based on the results of the identification of haram materials in each process in the activity, the Halal Control Point (HCP) is obtained. The application of HCCP to the Tanah Liek Batik value chain has 13 critical points of haram products, which come from the process, facilities, and tools and materials used during the production process. This study also produces a Halal Value Chain framework in the Textile Industry. Applying this framework in the textile industry is expected to increase the number of halal-certified textile industries.

Recent advances in cognitive neuroscience have focused on using resting-state functional connectivity (RSFC) data from fMRI scans to more accurately predict human traits and behaviors. Traditional approaches generally analyze RSFC by correlating averaged time-series data across regions of interest (ROIs) or networks, which may overlook important spatial signal patterns. To address this limitation, we introduced a novel linear regression technique that estimates RSFC by predicting spatial brain activity patterns in a target ROI from those in a seed ROI. We applied both traditional and our novel RSFC estimation methods to a large-scale dataset from the Human Connectome Project and the Brain Genomics Superstruct Project, analyzing resting-state fMRI data to predict sex, age, personality traits, and psychological task performance. To enhance prediction accuracy, we developed an ensemble learner that combines these qualitatively different methods using a weighted average approach. Our findings revealed that hierarchical clustering of RSFC patterns using our novel method displays distinct whole-brain grouping patterns compared to the traditional approach. Importantly, the ensemble model, integrating these diverse weak learners, outperformed the traditional RSFC method in predicting human traits and behaviors. Notably, the predictions from the traditional and novel methods showed relatively low similarity, indicating that our novel approach captures unique and previously undetected information about human traits and behaviors through fine-grained local spatial patterns of neural activation. These results highlight the potential of combining traditional and innovative RSFC analysis techniques to enrich our understanding of the neural basis of human traits and behaviors.

Type 2 diabetes (T2D) progresses over time, and to achieve and maintain adequate glucose control, many people eventually require injectable therapies such as insulin. However, there can be significant barriers to the initiation of these medications, both from people living with T2D and from healthcare practitioners (HCPs). Misconceptions and misinformation relating to the potential risks and benefits of injectable therapies are common and can contribute to negative perceptions regarding their use. Additionally, HCPs are often unaware of the emotional burden associated with T2D. In particular, diabetes distress is a key contributory factor that needs to be addressed to alleviate fears before diabetes education can be successful. The onus is often on the HCP to initiate effective, individualized communication with each patient and make that person feel an active and equal participant in the management of their T2D. Shared decision-making has been demonstrated to improve understanding of the pathophysiology and treatment options, to increase risk awareness, adherence, and persistence, and to improve self-management behaviors (e.g., exercise, self-care) and patient satisfaction. While therapeutic inertia can result from both patient and HCP, HCPs need to bear the responsibility for escalating therapy when necessary. A proactive approach by the HCP, combined with shared decision-making and a patient-centric approach, are important for optimal T2D management; therefore, an open and effective relationship between the HCP and the person living with T2D is essential. This article is written by a person with T2D, a nurse practitioner/Certified Diabetes Care and Education Specialist, and a clinical endocrinologist, with the goal of providing a holistic view of the management experience, exploring patient needs and expectations, recognizing and avoiding HCP and patient barriers, and providing practical advice to HCPs to empower patients who would benefit from injectable therapy.Infographic and video abstract available for this article.

Nutrition has played a central role in the management and outcomes of people with cystic fibrosis (pwCF) since the 1970s. Advances in therapies and practices in recent decades have led to a significant change in the patient landscape with dramatic improvements in life expectancy, as well as quality of life, bringing with it new issues. Historically, cystic fibrosis was a condition associated with childhood and malnutrition; however, changes in patient demographics, nutritional assessment and fundamental nutritional management have evolved, and it has become an increasingly prevalent adult disease with new nutritional challenges, including obesity. This paper aims to describe these changes and the impact and challenges they bring for those working in this field. Nutritional professionals will need to evolve, adapt and remain agile to the wider range of situations and support required for a new generation of pwCF. Specialised nutrition support will continue to be required, and it will be additionally important to improve and optimise quality of life and long‐term health. Key points: Traditional cystic fibrosis dietary advice focused on a default high‐fat/high‐calorie intake with limited consideration for other important nutrients. The emerging new era approach should be individualised, flexible and with an emphasis on diversity and longevity.Historically, this population was predominantly undernourished or at risk of undernutrition, but with the success and impact of nutritional guidelines, multidisciplinary teams, screening and new therapies, overnutrition is becoming an increasing concern that requires attention.Significant improvements in life expectancy mean more people with cystic fibrosis are living into old age, bringing with it age‐related complications and new opportunities that require nutritional consideration from childhood. [ABSTRACT FROM AUTHOR]

Abstract Background Anti‐obesity medications (AOMs) may provide a viable option for obesity management. However, little is known about the use of AOMs in persons with SCI/D. Objective Describe health care providers' (HCPs) views about barriers to AOM use in persons living with SCI/D. Methods Descriptive qualitative design using in‐depth interviews Descriptive statistics were used to calculate demographic and employment characteristics. Interviews were audio‐recorded and transcribed verbatim. Transcripts were coded and analyzed using Braun and Clarke's (2006) six thematic analysis phases. Results HCPs (n = 12) were from 11 different nationwide facilities. Most HCPs were male (75%), a large majority were white (67%), and most were 26–49 years of age. Participants were dietitians (75%), physicians (17%), and psychologists (8%). HCPs ranged from 1.5 to 15 years of providing SCI/D care. HCPs described four main thematic barriers to AOM use in persons with SCI/D: (1) AOM side effects that are especially concerning in persons with SCI/D; (2) AOMs contribute to poor eating habits; (3) availability, accessibility, and administration; and (4) lack of evidence, clinical agreement, and knowledge about AOM use in the SCI/D population. Conclusions There are several potential barriers to AOM use in the SCI/D population. Barriers include AOM side effects which may cause or exacerbate conditions that are already concerns in persons with SCI/D, such as bowel and skin problems, and muscle loss. SCI/D HCPs reported a lack of evidence about AOM use in persons with SCI/D, but interest in obtaining more knowledge.

Accurate psychiatric risk assessment requires biomarkers that are both stable and adaptable to development. Functional network connectivity (FNC), which steadily reconfigures over time, potentially contains abundant information to assess psychiatric risks. However, the absence of suitable analytical methodologies has constrained this area of investigation. We investigated the brainwide risk score (BRS), a novel FNC-based metric that contrasts the relative distances of an individual's FNC to that of psychiatric disorders versus healthy control references. To generate group-level disorder and healthy control references, we utilized a large brain imaging dataset containing 5231 total individuals diagnosed with schizophrenia, autism spectrum disorder, major depressive disorder, and bipolar disorder and their corresponding healthy control individuals. The BRS metric was employed to assess the psychiatric risk in 2 new datasets: Adolescent Brain Cognitive Development (ABCD) Study (n = 8191) and Human Connectome Project Early Psychosis (n = 170). The BRS revealed a clear, reproducible gradient of FNC patterns from low to high risk for each psychiatric disorder in unaffected adolescents. We found that low-risk ABCD Study adolescent FNC patterns for each disorder were strongly present in over 25% of the ABCD Study participants and homogeneous, whereas high-risk patterns of each psychiatric disorder were strongly present in about 1% of ABCD Study participants and heterogeneous. The BRS also showed its effectiveness in predicting psychosis scores and distinguishing individuals with early psychosis from healthy control individuals. The BRS could be a new image-based tool for assessing psychiatric vulnerability over time and in unaffected individuals, and it could also serve as a potential biomarker, facilitating early screening and monitoring interventions. [ABSTRACT FROM AUTHOR]

Heat collection plates (HCP) are installed above sprinkler heads in some tall halls in the Asia-Oceania region to give faster thermal actuation. In this study, experiments were thus conducted in a fire chamber to determine thermal activation times of sprinkler heads with and without HCP. Three HCP with different diameters were selected and tested with pendent fast response liquid-in-bulb sprinkler heads. A total of 48 sprinklers heads were studied under different conditions of height and pool fire size. The HCP was found to reduce sprinkler activation time in a fire chamber test by up to 61%. Thermal activation time of sprinkler heads was also investigated by the common plunge test in a wind tunnel. Results indicate that activation was delayed by 5%, 18%, and 221% on average by the three HCP. An HCP of pie plate shape with small diameter would alter the physical scenario of heating up the heat sensing element of sprinkler heads assumed in the plunge test. Therefore, the effect of HCP cannot be appropriately assessed in a wind tunnel. [ABSTRACT FROM AUTHOR]

Hexagonal close-packed (HCP) metals, particularly Zirconium (Zr), Titanium (Ti), and Magnesium (Mg) alloys, have attracted significant attention due to their unique properties and wide-ranging applications in the aerospace, biomedical, and energy industries. This review paper provides a comprehensive analysis of the microstructural and textural evolution in these HCP materials under various conditions, including rolling, extrusion, drawing, and annealing. The focus of the present work lies on the deformed microstructure and texture development in HCP metals, thus elucidating the fundamental mechanisms that govern their response to mechanical stress. The interaction between dislocation movements, twinning, and slip systems is discussed in detail, illustrating how these factors contribute to the anisotropic behavior characteristic of low-symmetry HCP structures. Unlike high-symmetry metals, deformation in Zr alloys depends on the activation of various slips and twin deformation modes, which are sensitive to crystallographic orientation and strain. Like Zr, Ti alloys present a more complex deformation behavior, heavily influenced by their crystallographic orientation. The most common deformation textures in Ti alloys include split-transverse direction (split-TD), split-rolling direction (split-RD), and normal direction (ND) symmetric basal fiber textures. These textures emerge due to the activation of multiple slip systems and twinning, which are dependent on external factors such as temperature, strain rate, and alloy composition. For Mg alloys, the poor formability and brittleness associated with the dominance of the basal slip system under ambient conditions is a critical material development challenge. The activation of non-basal slip systems introduces complexities in controlling texture and microstructure. However, their activation is crucial for optimizing mechanical properties such as strength and fatigue resistance. The tendency for twinning in Mg alloys further complicates their deformation behavior, leading to challenges in ensuring uniform mechanical performance. Modifying the alloy composition, grain size, and texture can additionally influence the activation of these deformation mechanisms. This review further explores the roles of dynamic recrystallization and grain growth in tailoring mechanical properties, with a particular focus on microstructure and texture evolution during annealing. Through this detailed review, we aim to present a thorough understanding of the microstructural and textural evolution in HCP materials, thereby guiding future research and industrial applications.

The anisotropic plasticity constants of the CPB06 criterion for Ti64, previously identified with experiments performed in all three dimensions, are applied here to evaluate the effect of the direct and inverse calibration strategies of the tensile-compression asymmetry parameter k on the predictive behavior of large deformations of the hexagonal close-packed (hcp) alloy. The direct calibration strategy is based on model fitting with experimental strain hardening data up to the onset of plastic instability. The inverse calibration strategy reduces prediction errors of the load-displacement curves of both the cylindrical bar tensile and the elliptical cylinder compression tests. The results provide interesting insights into the identification of the laws modeling large deformations of hcp materials.

ABSTRACT: The type VI secretion system (T6SS) of avian pathogenic Escherichia coli (APEC) can affect the functions of eukaryotic cells by secreting or injecting effectors. Hemolysin co-regulatory protein (Hcp), one of the markers of the T6SS, is both a structural protein and an effector protein of the T6SS. According to previous studies, mitochondria in eukaryotic cells are targeted by pathogenic bacteria. However, little is known about the regulation of mitochondria in eukaryotic host cells by the T6SS effector protein Hcp of APEC. In our study, DF-1 cells co-incubated with Hcp2a protein for 6 h showed decreased mitochondrial membrane potential, increased Ca2+ concentration, and increased cellular reactive oxygen species (ROS) levels. We therefore conclude that Hcp2a protein causes dysfunction to mitochondria in DF-1 cells. To explain the mechanism that causes mitochondrial dysfunction, we reanalyzed the Hcp2a interaction protein dataset in DF-1 cells, and the Leucine zipper EF-hand-containing transmembrane protein 1 (LETM1), which is associated with mitochondria, was screened. The protein and molecular docking results showed that Hcp2a protein and LETM1 protein have better binding. Finally, subcellular localization results showed that Hcp2a was localized to mitochondria. In summary, Hcp2a effector proteins caused dysfunction to DF-1 cellular mitochondria, and we hypothesize that the interaction of Hcp2a protein with LETM1 protein induces mitochondrial dysfunction and promotes mitochondrial localization of Hcp2a in DF-1 cells.

A large number of companies observe polysorbate (PS) degradation and associated (sub‐)visible particle formation in biological drug formulations, which compromise the stability of the drug product, ultimately posing a risk toward delivering innovative medicines to patients. The main culprits of PS degradation are hydrolytic host cell proteins (HCPs) originating from the production cell lines, which are mostly Chinese hamster ovary (CHO) cell derived. Here, a small portion of particularly difficult‐to‐remove HCPs—mainly lipases—cause hydrolytic cleavage of PS resulting in the accumulation of free fatty acid aggregates/particles. One possible mitigation strategy is the removal of such critical HCPs in the production cell line. Multigene regulation can be achieved via microRNAs (miRNAs) thereby serving as a smart tool to reduce the expression of different target genes using a single miRNA. To enable a tailored gene regulation of multiple specific target lipases self‐designed and non‐naturally occurring artificial miRNAs (amiRNA) can be designed. Based on micro‐conserved regions in the mRNA sequence of two sets of target HCPs, we provide a proof‐of‐concept for a simultaneous multi‐lipase knockdown in CHO cells using single amiRNAs. By this, we were not only able to reduce PS degradation but laid the foundation to expand this tool to other areas of cell line phenotype engineering. [ABSTRACT FROM AUTHOR]

The electronic, magnetic, mechanical, and other properties of crystalline substances are determined by their structure, i.e., by the periodicity and symmetry of the lattice; therefore, the determination of the structure is an important stage in the study of the characteristics of such materials. This paper considers a number of metals having a crystal lattice of the hexagonal closely packed (HCP) structural type: beryllium, cerium, cobalt, dysprosium, erbium, gadolinium, hafnium, holmium, lanthanum, lutetium, magnesium, neodymium, osmium, praseodymium, rhenium, ruthenium, scandium, terbium, titanium, thallium, thulium, yttrium, and zirconium. The application of the annealing simulation algorithm to find the metric parameters of the materials under consideration is shown using the close packing model, which is widely used in crystallographic calculations. The in-house software implementation of the simulated annealing algorithm presented in this paper allows us to determine the coordinates of the atoms included in the unit cell of the crystal lattice, as well as calculate the lattice constants and the packing density of atoms in the crystal cell of the HCP structural type using the given chemical formula and spatial symmetry group. These structural characteristics can be used as the input parameters in modeling the electronic, magnetic, and other properties of the considered materials. This paper compares the values of the crystal lattice constants obtained as a result of the numerical simulation with the published data. [ABSTRACT FROM AUTHOR]

Abstract The type VI secretion system (T6SS) is a secretion apparatus widely found in pathogenic Gram-negative bacteria and is important for competition among various bacteria and host cell pathogenesis. Hcp is a core component of functional T6SS and transports toxic effectors into target cells by assembling to form tube-like structures. Studies have shown that Hcp simultaneously acts as an effector to influence cellular physiological activities; however, the mechanism of its activity in host cells remains unclear. To investigate the target of effector protein Hcp2a in a chicken fibroblast cell line, we first detected the subcellular localization of Hcp2a in DF-1 cells by indirect immunofluorescence assay. The results showed that Hcp2a protein was localized in the endoplasmic reticulum of DF-1 cells. We also used a streptavidin–biotin affinity pull-down assay combined with LC–MS/MS to screen DF-1 cell lysates for proteins that interact with Hcp2a and analyze the cellular functional pathways affected by them. The results showed that Hcp2a interacted with 52 DF-1 cellular proteins that are involved in multiple intracellular pathways. To further explore the mechanism of Hcp2a protein targeting the endoplasmic reticulum of DF-1 cells, we screened three endoplasmic reticulum-associated proteins (RSL1D1, RPS3A, and RPL23) from 52 prey proteins of Hcp2a for protein–protein molecular docking analysis. The docking analysis showed that the effector protein Hcp2a and the RPL23 protein had good complementarity. Overall, we propose that Hcp2a has strong binding activity to the RPL23 protein in DF-1 cells and this may help Hcp2a anchor to the endoplasmic reticulum in DF-1 cells.

Introduction: COVID-19 seroprevalence studies for Health Care Personnel (HCP) can provide relevant information on the proportion of people who have experienced a recent or past infection and provide information about populations that may be immune and potentially protected. Aim of the study was to determine the seroprevalence of COVID-19 and associated factors among HCP and to correlate COVID-19 antibody results with respect to time duration since laboratory confirmed positive COVID-19 test and vaccination. Methodology: A prospective, cross-sectional study in HCP working at Shree Krishna Hospital and Pramukhswami Medical College, Karamsad was conducted at Microbiology section of Central Diagnostic Laboratory (CDL). Following approval from Institutional Ethics Committee, the study was conducted from March 2021- June 2022. The serological test to measure COVID-19 IgG antibody was done by Enzyme Linked Fluorescent Assay (ELFA, VIDAS, Biomerieux) in 118 eligible HCP. Antibody response was correlated with age, gender, occupation, work area, symptoms, test requests and test results. Correlation of COVID-19 antibody results with respect to time duration since laboratory confirmed positive COVID-19 test and after vaccination was done. All the data was entered and analysed in Microsoft Excel 2010. Results: Seroprevalence of COVID-19 was found to be 97.45% (115/118) in HCP. Seroprevalence was 100 % in all the age groups except 18-30 and 41-50 years; 100% in all the professional categories except consultant doctors and resident doctors; 100% in HCP working in non-COVID-19 unit and 100% in participants not tested for COVID-19 test. 13 (37.14%) HCP were seropositive beyond 11 months duration after positive COVID-19 test. In 49 (44.54%) HCP, SARS-CoV-2 IgG antibody were found beyond 7 months duration after COVID-19 vaccine. SARS-CoV-2 IgG antibody were positive in eight (6.96%) non-vaccinated and 107 (93.04%) vaccinated participants. Conclusions: COVID-19 infection and/or COVID-19 vaccination might have contributed to excellent seroprevalence in health care personnel (HCP) of our hospital. Persistence of SARS-CoV-2 IgG antibody for longer duration was observed in HCP with past infection as well as past vaccination. Natural COVID-19 infection might have contributed to seropositivity in a few nonvaccinated, asymptomatic & RTPCR/RAT negative/not done HCP. [ABSTRACT FROM AUTHOR]

In this paper we demonstrate a generalized and simplified pipeline called axonal spectrum imaging (AxSI) for in-vivo estimation of axonal characteristics in the human brain. Whole-brain estimation of the axon diameter, in-vivo and non-invasively, across all fiber systems will allow exploring uncharted aspects of brain structure and function relations with emphasis on connectivity and connectome analysis. While axon diameter mapping is important in and of itself, its correlation with conduction velocity will allow, for the first time, the explorations of information transfer mechanisms within the brain. We demonstrate various well-known aspects of axonal morphometry (e.g., the corpus callosum axon diameter variation) as well as other aspects that are less explored (e.g., axon diameter-based separation of the superior longitudinal fasciculus into segments). Moreover, we have created an MNI based mean axon diameter map over the entire brain for a large cohort of subjects providing the reference basis for future studies exploring relation between axon properties, its connectome representation, and other functional and behavioral aspects of the brain. [ABSTRACT FROM AUTHOR]

A comparative study of the sorption behavior of europium, a chemical analogue of trivalent actinides, and uranium was performed on hydrated cement paste (HCP) CEM I and calcium-silicate-hydrates (CSH) phase. Kinetic experiments proved that Eu sorption is faster than that of U depending on the phase ratio L/S and the sorption material, whereas EDTA has no significant effect. Same conclusions can be made for equilibrium experiments with HCP and U while with Eu EDTA clearly influenced the distribution ratio Rd with sorption reduction factor (SRF) below 0.5. Uranium sorption on CSH compared to HCP is higher with SRF above 1.2. [ABSTRACT FROM AUTHOR]

Purpose: To combine a new two‐stage N/2 ghost correction and an adapted L1‐SPIRiT method for reconstruction of 7T highly accelerated whole‐brain diffusion MRI (dMRI) using only autocalibration scans (ACS) without the need of additional single‐band reference (SBref) scans. Methods: The proposed ghost correction consisted of a 3‐line reference approach in stage 1 and the reference‐free entropy method in stage 2. The adapted L1‐SPIRiT method was formulated within the 3D k‐space framework. Its efficacy was examined by acquiring two dMRI data sets at 1.05‐mm isotropic resolutions with a total acceleration of 6 or 9 (i.e., 2‐fold or 3‐fold slice and 3‐fold in‐plane acceleration). Diffusion analysis was performed to derive DTI metrics and estimate fiber orientation distribution functions (fODFs). The results were compared with those of 3D k‐space GRAPPA using only ACS, all in reference to 3D k‐space GRAPPA using both ACS and SBref (serving as a reference). Results: The proposed ghost correction eliminated artifacts more robustly than conventional approaches. Our adapted L1‐SPIRiT method outperformed 3D k‐space GRAPPA when using only ACS, improving image quality to what was achievable with 3D k‐space GRAPPA using both ACS and SBref scans. The improvement in image quality further resulted in an improvement in estimation performances for DTI and fODFs. Conclusion: The combination of our new ghost correction and adapted L1‐SPIRiT method can reliably reconstruct 7T highly accelerated whole‐brain dMRI without the need of SBref scans, increasing acquisition efficiency and reducing motion sensitivity. [ABSTRACT FROM AUTHOR]

Functional connectivity studies increasingly turn to machine learning methods, which typically involve fitting a connectome-wide classifier, then conducting post hoc interpretation analyses to identify the neural correlates that best predict a dependent variable. However, this traditional analytic paradigm suffers from two main limitations. First, even if classifiers are perfectly accurate, interpretation analyses may not identify all the patterns expressed by a dependent variable. Second, even if classifiers are generalizable, the patterns implicated via interpretation analyses may not replicate. In other words, this traditional approach can yield effective classifiers while falling short of most neuroscientists’ goals: pinpointing the neural correlates of dependent variables. We propose a new framework for multivariate analysis, ConnSearch, which involves dividing the connectome into components (e.g., groups of highly connected regions) and fitting an independent model for each component (e.g., a support vector machine or a correlation-based model). Conclusions about the link between a dependent variable and the brain are based on which components yield predictive models rather than on interpretation analysis. We used working memory data from the Human Connectome Project (N = 50–250) to compare ConnSearch with four existing connectome-wide classification/interpretation methods. For each approach, the models attempted to classify examples as being from the high-load or low-load conditions (binary labels). Relative to traditional methods, ConnSearch identified neural correlates that were more comprehensive, had greater consistency with the WM literature, and better replicated across datasets. Hence, ConnSearch is well-positioned to be an effective tool for functional connectivity research.

Abstract Background Bacteria deliver effector proteins into the host cell via a secretory system that can directly act on the target to cause disease. As an important pipeline structural protein of the type VI secretion system (T6SS) complex, Hcp acts together with other virulence factors in the target cell. There is growing evidence that T6SS plays a key role in the pathogenic mechanism of APEC. However, the regulatory function played by the effector protein Hcp during its interaction with host cells is not clear. Here, tandem mass tag (TMT) analysis was used to quantify the proteins affected by increased expression of Hcp2a in DF-1 cells. Results The host response was significantly different between the overexpression and null groups at the protein level. A total of 195 differentially expressed proteins (DEPs) were detected in the overexpression group (upregulated, n = 144, downregulated, n = 51). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological functions and pathways of differentially expressed proteins. The results showed that these DEPs were mainly enriched in RNA degradation, spliceosome, and mRNA surveillance pathways. Conclusions This study suggests that Hcp2a, the effector protein of APEC, plays an important role in regulating mRNA splicing and protein quality control in DF-1 cells. These findings provide useful clues to elucidate the pathogenic mechanism of effector protein Hcp2a on host target cells.

The Heterogeneous Network (HetNet) based ultra-dense network is the possible solution to cope up with the exponential growth in data traffic. The HetNet deployment provides benefits of load balancing, better connectivity and higher data rate to the users. However, the diversity in transmit power results in downlink (DL)/uplink (UL) imbalance and poses a serious issue in mobility management. Adoption of DL/UL decoupled (DUDe) handover (HO) method where DL and UL HO occurs separately which could possibly improve the user's quality of service and network performance. The control parameters involved in this DUDe HO procedure should be properly configured to achieve the expected performance. In this work, simulation analysis has been carried out to explore the dependency of these control parameters on various factors such as Inter-Site-Distance (ISD), velocity and offloading. The analytical results provide interesting insights about the control parameter configuration in decoupled wireless connection. From the analysis results, measurement configuration strategy has been developed to configure the HCP in decoupled HO method. The results show the proposed method achieves increase in dwell time when compared to the legacy coupled HO method. [ABSTRACT FROM AUTHOR]

Sliding wear results indicated that although the wear rates increased with a decrease in the hardness of the samples, the wear rate of the strength–ductility matching sample with a recrystallization volume fraction of 75 % (V75) abnormally decreased. High strength and low dislocation density in the strength–ductility matching sample were conducive to the formation of the hexagonal close-packed (HCP) phase. However, the high dislocation density in the sample with a low recrystallization volume fraction of 26 % (V26) and the low stress generated during wear testing due to the low strength of the sample with a high recrystallization volume fraction of 87 % (V87) were not conducive to the production of the HCP phase. The thickness of the HCP phase in the subsurface of V75 was 21 μm, which was 2.3 times that of V87 (9 μm) after wear. The generation of the HCP phase not only improved the work-hardening ability of the sample but also led to grain refinement, which was beneficial for acquiring a thicker ultrafine grain layer. The inferior plasticity of V26 and the deformability due to the low strength of V87 were not favorable for the formation of a stable dynamic oxide film. The higher strength resisted deformation, and outstanding ductility reduced the probability of crack generation in V75, which demonstrated a thicker deformation layer and a complete dynamic oxide film after wear, conducive to reducing the wear rate. The proposed bimodal-structural material design strategy provides an effective method for designing materials with high wear resistances. • Samples with matching strength and ductility can obtain the best wear resistance. • High yield and low dislocation density are beneficial to the formation of HCP phase in the wear subsurface. • High yield and high toughness are beneficial to the retention of dynamic dynamic oxide film. [ABSTRACT FROM AUTHOR]

In this paper, the reliability of two nondestructive corrosion detection methods, Half-Cell Potential (HCP) and Electrical Resistivity (ER), was evaluated, considering the Weight Loss (WL) as the reference method. The specimens prepared for this work were placed in Al-Nasiriya Power Station where subjected to three different exposure conditions. They were high relative humidity, high temperature T and laboratory setting R. The concrete mixes included four chloride contents, 0 %, 1.5 %, 3 % and 4 % by weight of cement to generate multiple corrosion degrees. The results showed that exposure to high temperatures has slightly increased the corrosion activity of the T specimens. While the exposure to high relative humidity has clearly increased the corrosion probability of the RH specimens, comparing with the reference R specimens. However, for such environmental conditions, it was found that the reliabilities of the HCP and the ER techniques still questionable and need further investigation.

Cyclic AMP (cAMP) and cAMP receptor protein (CRP) system controls catabolic enzyme expression based on metabolite concentrations in bacteria. Hemolysin co-regulatory protein (Hcp) is well known as a molecular chaperone for virulence factor secretion of the type VI secretion system (T6SS). However, the intracellular role of Hcp involving in bacterial physiological processes remains unknown. To clarify that, we constructed a single hcp mutant strain and analyzed their effects on the physiological processes of Vibrio alginolyticus. The omics results revealed the extensive involvement of Hcp in the catabolic metabolism in bacteria. Simultaneously, Hcp1 and Hcp2 played opposing regulatory roles on the bacterial growth, biofilm formation, and intracellular cAMP-CRP levels during cultivation in a glucose medium. Furthermore, the interacting protein screening and co-immunoprecipitation (Co-IP) assays confirmed that the glucose-specific phosphoenolpyruvate (PEP)-phosphotransferase system (PTS) enzyme IIA component (EIIAglc) was a key interacting partner with Hcp proteins as well as class I adenylyl cyclase (AC-I) in Vibrio alginolyticus. These results indicated that, to achieve cellular homeostasis, Hcp1 and Hcp2 might exert antagonistic and synergistic effects, respectively, on the interaction between EIIAglc and AC thus cooperatively regulating intracellular cAMP-CRP production. • Hcp is extensively involved in substrate transport and metabolism processes. • EIIAglc is the common interacting protein among Hcp1, Hcp2 and adenylate cyclase. • Cooperative regulation of Hcp1 and Hcp2 on survival and pathogenicity by cAMP-CRP. [ABSTRACT FROM AUTHOR]

The complex deformation of magnesium (Mg) and its alloys has been the focus of many studies in lightweight technologies. In this paper, spherical micro-indentation tests followed by post-test electron microscopy were carried out on large grain pure Mg to isolate the effects of crystal orientation on the activation of deformation along different slip or twinning systems. Both pre- and post-indentation crystal orientations were measured using electron backscatter diffraction (EBSD). The pre-indentation orientations were mapped into a crystal plasticity finite element (CPFE) model to further analyze the results. It is shown that the resulting deformation twinning and the degree of indentation-induced misorientation were strongly correlated with the crystal orientation in the region of the indentation. Depending on the crystal orientation, multiple waves of basal slip were observed to form asymmetrically around the indents. These slip bands lead to more than 12° lattice rotations that are captured by CPFE modeling. For the first time, it is shown that indentation can lead to significant out-of-plane displacement field that can induce twin nucleation at the interface of far-field (>100 μm) neighbouring grains. CPFE simulations indicate that maintaining far-field strain compatibility leads to the nucleation of twins rather than a slip transfer or slip-induced twinning mechanism. • CPFE and micro indentation are used to characterize deformation mechanisms of pure magnesium. • EBSD is used to measure orientation distribution before and after indentation within individual grains. • Asymmetric plastic deformation occurs with the formation of slip bands, twins, and misorientation fields around indents. • A new mechanism for nucleation of twins in neighbouring grains is discovered. • Numerical modeling shows this nucleation results from out-of-plane displacement, not a slip-induced twinning. [ABSTRACT FROM AUTHOR]

The type VI secretion system (T6SS) is a secretion apparatus widely found in pathogenic Gram-negative bacteria and is important for competition among various bacteria and host cell pathogenesis. Hcp is a core component of functional T6SS and transports toxic effectors into target cells by assembling to form tube-like structures. Studies have shown that Hcp simultaneously acts as an effector to influence cellular physiological activities; however, the mechanism of its activity in host cells remains unclear. To investigate the target of effector protein Hcp2a in a chicken fibroblast cell line, we first detected the subcellular localization of Hcp2a in DF-1 cells by indirect immunofluorescence assay. The results showed that Hcp2a protein was localized in the endoplasmic reticulum of DF-1 cells. We also used a streptavidin–biotin affinity pull-down assay combined with LC–MS/MS to screen DF-1 cell lysates for proteins that interact with Hcp2a and analyze the cellular functional pathways affected by them. The results showed that Hcp2a interacted with 52 DF-1 cellular proteins that are involved in multiple intracellular pathways. To further explore the mechanism of Hcp2a protein targeting the endoplasmic reticulum of DF-1 cells, we screened three endoplasmic reticulum-associated proteins (RSL1D1, RPS3A, and RPL23) from 52 prey proteins of Hcp2a for protein–protein molecular docking analysis. The docking analysis showed that the effector protein Hcp2a and the RPL23 protein had good complementarity. Overall, we propose that Hcp2a has strong binding activity to the RPL23 protein in DF-1 cells and this may help Hcp2a anchor to the endoplasmic reticulum in DF-1 cells. [ABSTRACT FROM AUTHOR]

Aeromonas salmonicida, a psychrophilic bacterial pathogen, is widely distributed in marine freshwater, causing serious economic losses to major salmon farming areas in the world. At present, it is still one of the most important pathogens threatening salmon farming. Hcp (haemolysin-coregulated protein) is an effector protein in the type-VI secretion system (T6SS), which is secreted by T6SS and functions as its structural component. The results of our previous genomic sequencing showed that hcp existed in the mesophilic A. salmonicida SRW-OG1 isolated from naturally infected Epinephelus coioides. To further explore the role of Hcp in A. salmonicida SRW-OG1, we constructed an hcp-RNAi strain and verified its effect on the virulence of A. salmonicida. The results showed that compared with the wild strain, the hcp-RNAi strain suffered from different degrees of decreased adhesion, growth, biofilm formation, extracellular product secretion, and virulence. It was suggested that hcp may be an important virulence gene of A. salmonicida SRW-OG1. [ABSTRACT FROM AUTHOR]

Abstract Background and rationale Obesity is associated with the development and progression of many diseases. Understanding and management of obesity have become increasingly important; however, a knowledge gap remains between how healthcare providers (HCPs) consider weight‐loss treatment and the importance of weight loss for improving obesity‐related diseases. Objective The objective of this study was to investigate how HCPs assess obesity, how they interpret the relationship between obesity and 12 recognized co‐morbidities of obesity (excluding diabetes), and their view about the value of various weight‐loss therapies. Methods This was a cross‐sectional, non‐interventional, descriptive study. Participants were medical doctors (HCPs) from eight European countries. Results Eighty‐nine percent of the 197 HCPs that completed the survey considered obesity a disease. For most of the 12 obesity‐related diseases under consideration, a majority of HCPs agreed that weight loss could reverse the disease or prevent progression. Among HCPs who have recommended weight loss, lifestyle interventions were by far the most common recommendation. However, more than three out of four HCPs stated that they would be likely to prescribe anti‐obesity medications if available and reimbursed. Conclusion Most HCPs in this survey consider obesity a disease that needs to be treated. However, the majority of HCPs appear to prefer recommending lifestyle changes, although it is well documented that weight loss obtained by lifestyle changes is difficult to maintain. These results underscore the need for improved education of HCPs involved in the treatment of obesity‐related diseases.

Background: Bacteria deliver effector proteins into the host cell via a secretory system that can directly act on the target to cause disease. As an important pipeline structural protein of the type VI secretion system (T6SS) complex, Hcp acts together with other virulence factors in the target cell. There is growing evidence that T6SS plays a key role in the pathogenic mechanism of APEC. However, the regulatory function played by the effector protein Hcp during its interaction with host cells is not clear. Here, tandem mass tag (TMT) analysis was used to quantify the proteins affected by increased expression of Hcp2a in DF-1 cells. Results: The host response was significantly different between the overexpression and null groups at the protein level. A total of 195 differentially expressed proteins (DEPs) were detected in the overexpression group (upregulated, n = 144, downregulated, n = 51). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological functions and pathways of differentially expressed proteins. The results showed that these DEPs were mainly enriched in RNA degradation, spliceosome, and mRNA surveillance pathways. Conclusions: This study suggests that Hcp2a, the effector protein of APEC, plays an important role in regulating mRNA splicing and protein quality control in DF-1 cells. These findings provide useful clues to elucidate the pathogenic mechanism of effector protein Hcp2a on host target cells. [ABSTRACT FROM AUTHOR]

A type VI secretion system (T6SS) gene cluster has been reported in Acidovorax citrulli. Research on the activation conditions, functions, and the interactions between key elements in A. citrulli T6SS is lacking. Hcp (Hemolysin co-regulated protein) is both a structural protein and a secretion protein of T6SS, which makes it a special element. The aims of this study were to determine the role of Hcp and its activated conditions to reveal the functions of T6SS. In virulence and colonization assays of hcp deletion mutant strain Δhcp, tssm (type VI secretion system membrane subunit) deletion mutant strain Δtssm and double mutant ΔhcpΔtssm, population growth was affected but not virulence after injection of cotyledons and seed-to-seedling transmission on watermelon. The population growth of Δhcp and Δtssm were lower than A. citrulli wild type strain Aac5 of A. citrulli group II at early stage but higher at a later stage. Deletion of hcp also affected growth ability in different culture media, and the decline stage of Δhcp was delayed in KB medium. Biofilm formation ability of Δhcp, Δtssm and ΔhcpΔtssm was lower than Aac5 with competition by prey bacteria but higher in KB and M9-Fe3+ medium. Deletion of hcp reduced the competition and survival ability of Aac5. Based on the results of Western blotting and qRT-PCR analyses, Hcp is activated by cell density, competition, ferric irons, and the host plant. The expression levels of genes related to bacterial secretion systems, protein export, and several other pathways, were significantly changed in the Δhcp mutant compared to Aac5 when T6SS was activated at high cell density. Based on transcriptome data, we found that a few candidate effectors need further identification. The phenotypes, activated conditions and transcriptome data all supported the conclusion that although there is only one T6SS gene cluster present in the A. citrulli group II strain Aac5, it related to multiple biological processes, including colonization, growth ability, competition and biofilm formation. [ABSTRACT FROM AUTHOR]

Mobility management is an essential process in mobile networks to ensure a high quality of service (QoS) for mobile user equipment (UE) during their movements. In fifth generation (5G) and beyond (B5G) mobile networks, mobility management becomes more critical due to several key factors, such as the use of Millimeter Wave (mmWave) and Terahertz, a higher number of deployed small cells, massive growth of connected devices, the requirements of a higher data rate, and the necessities for ultra-low latency with high reliability. Therefore, providing robust mobility techniques that enable seamless connections through the UE's mobility has become critical and challenging. One of the crucial handover (HO) techniques is known as mobility robustness optimization (MRO), which mainly aims to adjust HO control parameters (HCPs) (time-to-trigger (TTT) and handover margin (HOM)). Although this function has been introduced in 4G and developed further in 5G, it must be more efficient with future mobile networks due to several key challenges, as previously illustrated. This paper proposes a Robust Handover Optimization Technique with a Fuzzy Logic Controller (RHOT-FLC). The proposed technique aims to automatically configure HCPs by exploiting the information on Reference Signal Received Power (RSRP), Reference Signal Received Quality (RSRQ), and UE velocity as input parameters for the proposed technique. The technique is validated through various mobility scenarios in B5G networks. Additionally, it is evaluated using a number of major HO performance metrics, such as HO probability (HOP), HO failure (HOF), HO ping-pong (HOPP), HO latency (HOL), and HO interruption time (HIT). The obtained results have also been compared with other competitive algorithms from the literature. The results show that RHOT-FLC has achieved considerably better performance than other techniques. Furthermore, the RHOT-FLC technique obtains up to 95% HOP reduction, 95.8% in HOF, 97% in HOPP, 94.7% in HOL, and 95% in HIT compared to the competitive algorithms. Overall, RHOT-FLC obtained a substantial improvement of up to 95.5% using the considered HO performance metrics. [ABSTRACT FROM AUTHOR]

Salmonella Entertidis (SE) often causes persistent infections and egg contamination in laying ducks. Hcp, the core structural and effector proteins of the Type VI Secretion System (T6SS) in SE, contributes to bacterial invasion, adhesion and virulence. However, little is known about the effect of Hcp on the host’s infection responses and egg contamination incidences in duck. Herein, we generated an hcp deletion mutant SE MY1△hcp and detected its ability to invade duck granulosa cells (dGCs) and contaminate eggs. In comparison with MY1-infected group, the SE adhesion decreased by 15.96% in MY1△hcp-infected dGCs, and the apoptosis in MY1△hcp-infected dGCs decreased by 26.58% and 30.99% at 3 and 6 hours postinfection, respectively. However, the expression levels of immunogenic genes TLR4, NOD1, TNFα, IL-1β and proinflammatory cytokines IL-6, IL-1β, TNF-α release were markedly lower in the dGCs inoculated with MY1△hcp than that of the wild type. Besides, the laying ducks were challenged with MY1 or MY1△hcp in vivo, respectively. The lower egg production and higher egg contamination were observed in MY1-infected ducks in comparison with MY1△hcp-infected birds. Furthermore, the host’s infection response of differentially abundant proteins (DAPs) to Salmonella effector Hcp was identified using quantitative proteomics. A total of 164 DAPs were identified between the MY1- and MY1△hcp-infected cells, which were mainly engaged in the immune, hormone synthesis, cell proliferation and cell apoptotic process. Among them, STAT3, AKT1, MAPK9, MAPK14, and CREBBP were the center of the regulatory network, which might serve as key host response regulators to bacterial Hcp. In conclusion, we demonstrated that effector Hcp contributed to not only SE invasion, induction of dGCs apoptosis, and trigger of immune responses, but also enhanced contamination incidences. Also, the STAT3, AKT1, MAPK9, MAPK14, and CREBBP were identified as host’s infection response regulators of bacterial Hcp in duck. Overall, these results not only offered a novel evidence of SE ovarian transmission but also identified some promising candidate regulators during SE infection.

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally followed a linear decline from 5 to 21 years of age, except for three functional networks that displayed nonlinear trajectories. We found no main effect of sex or age by sex interaction for any network. Earlier pubertal timing was associated with reduced mean CT and CT in seven networks. We also found a significant age by maternal education interaction for mean CT across cortex and CT in the dorsal attention network, where higher levels of maternal education were associated with steeper age-related decreases in CT. Taken together, our results suggest that these biological and environmental variations may impact the emerging functional connectome.

Cognitive reserve (CR) has been introduced to explain individual differences in susceptibility to cognitive or functional impairment in the presence of age or pathology. We developed a deep learning model to quantify the CR as residual variance in memory performance using the Structural Magnetic Resonance Imaging (sMRI) data from a lifespan healthy cohort. The generalizability of the sMRI-based deep learning model was tested in two independent healthy and Alzheimer's cohorts using transfer learning framework.Structural MRIs were collected from three cohorts: 495 healthy adults (age: 20-80) from RANN, 620 healthy adults (age: 36-100) from lifespan Human Connectome Project Aging (HCPA), and 941 adults (age: 55-92) from Alzheimer's Disease Neuroimaging Initiative (ADNI). Region of interest (ROI)-specific cortical thickness and volume measures were extracted using the Desikan-Killiany Atlas. CR was quantified by residuals which subtract the predicted memory from the true memory. Cascade neural network (CNN) models were used to train RANN dataset for memory prediction. Transfer learning was applied to transfer the T1 imaging-based model from source domain (RANN) to the target domains (HCPA or ADNI).The CNN model trained on the RANN dataset exhibited strong linear correlation between true and predicted memory based on the T1 cortical thickness and volume predictors. In addition, the model generated from healthy lifespan data (RANN) was able to generalize to an independent healthy lifespan data (HCPA) and older demented participants (ADNI) across different scanner types. The estimated CR was correlated with CR proxies such education and IQ across all three datasets.The current findings suggest that the transfer learning approach is an effective way to generalize the residual-based CR estimation. It is applicable to various diseases and may flexibly incorporate different imaging modalities such as fMRI and PET, making it a promising tool for scientific and clinical purposes.

• Grain average stress maps of notched specimens are measured using 3D-XRD. • Crystal plasticity finite element method is used to study the deformation behaviour. • Despite the inherent soft texture, grain orientations impact stress concentrations. • Mechanical constraints during grain-grain interactions led to material hardening. Texture, microstructure, and local grain neighbourhood contribute to the development of localized stresses in polycrystals. For hexagonal close-packed materials, crystal's elastic and plastic anisotropy can also be a major contributing factor, yet there is a paucity of experimental studies focusing on the extent of contribution of such parameters on the magnitude of localized stresses at microscales. This study focuses on addressing this knowledge gap by deforming double-edge-notched soft-textured α-zirconium specimens in-situ, while measuring grain scale tensorial stresses using high energy synchrotron X-ray diffraction. The specimens were subjected to cyclic loads to study the evolution of stresses in the vicinity of both shallow and deep notches. The soft-texture of the specimens is such that there are no c-axes of grains aligned along the macroscopic loading direction thereby inhibiting deformation twinning. The "as-measured" microstructures and notch geometries were imported into a crystal plasticity finite element model for further analysis. Results show that despite the absence of c-axes of grains aligned along loading direction, the developed stresses were substantially influenced by crystallographic orientations. Stress drop was observed near the onset of plasticity with further loading and the orientation and position effects were highlighted. A plastic deformation mechanism was revealed where, upon specimen loading, the mechanical constraints enforced during grain-grain interactions led to hardening. Accordingly, a parameter was devised to quantify the grain level hardening arising from this mechanism. It was shown that grain-scale stress concentration factors vary significantly before the onset of plasticity, but they settle in the plastic zone and with the progression of cycles. [ABSTRACT FROM AUTHOR]

Background and Aims: End-of-life (EoL) discussions can be difficult for seriously ill adolescents and young adults (AYAs). Researchers aimed to determine whether completing Voicing My CHOiCES (VMC)--a research-informed advance care planning (ACP) guide--increased communication with family, friends, or health care providers (HCPs), and to evaluate the experience of those with whom VMC was shared. Methods: Family, friends, or HCPs who the AYAs had shared their completed VMC with were administered structured interviews to assess their perception of the ACP discussion, changes in their relationship, conversation quality, and whether the discussion prompted changes in care. Open-ended responses underwent thematic analysis. Results: One-month post-completion, 65.1% of AYA had shared VMC completion with a family member, 22.6% with a friend, and 8.9% with an HCP. Among a sample of respondents, family (47%) and friends (33%) reported a positive change in their relationship with the AYA. Participant descriptions of the experience fell into five themes: positive experience (47%), difficult experience (44%), appreciated a guide to facilitate discussion (35%), provided relief (21%), and created worry/anxiety (9%). Only 1 HCP noted a treatment change. Family (76%), friends (67%), and HCP (50%) did not think the AYA would have discussed EoL preferences without completing VMC. Conclusions: VMC has potential to enhance communication about ACP between AYA and their family and friends, though less frequently with HCPs. Participants reported a positive change in their relationship with the AYA after discussing VMC, and described experiencing the conversation as favorable, even when also emotionally difficult. [ABSTRACT FROM AUTHOR]

In the control strategy for process related impurities in biopharmaceuticals, the enzyme linked immunosorbent assay (ELISA) is the method of choice for the quantification of host cell proteins (HCPs). Besides two dimensional‐western blots (2D‐WB), the coverage of ELISA antibodies is increasingly evaluated by affinity purification‐based liquid chromatography–tandem mass spectrometry (AP‐MS) methods. However, all these methods face the problem of unspecific binding issues between antibodies and the matrix, involving the application of arbitrarily defined thresholds during data evaluation. To solve this, a new approach (optimized AP‐MS) was developed in this study, for which a cleavable linker was conjugated to the ELISA antibodies enabling the subsequent isolation of specifically interacting HCPs. By comparing both approaches in terms of method variability and the number of false positive or negative hits, we could demonstrate that the optimized AP‐MS method is very reproducible and superior in the identification of antibody detection gaps, while previously described strategies suffered from over‐ or underestimating the coverage. As only antibody associated HCPs were identified, we demonstrated that the method is beneficial for hitchhiker analysis. Overall, the method described herein has proven as a powerful tool for reliable coverage determination of ELISA antibodies, without the need to arbitrarily exclude HCPs during the coverage evaluation. [ABSTRACT FROM AUTHOR]