bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D3 alters macrophage phenotype and endosomal trafficking markers in dairy cattle naturally infected with Mycobacterium avium subsp. paratuberculosis
Authors: Wherry Taylor L. T. , Dassanayake Rohana P. , Bannantine John P. , Mooyottu Shankumar , Stabel Judith R.
Published: October 2022

Macrophages are important host defense cells in ruminant paratuberculosis (Johne’s Disease; JD), a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). Classical macrophage functions of pathogen trafficking, degradation, and antigen presentation are interrupted in mycobacterial infection. Immunologic stimulation by 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) enhances bovine macrophage function. The present study aimed to investigate the role of vitamin D3 on macrophage phenotype and endosomal trafficking of MAP in monocyte-derived macrophages (MDMs) cultured from JD-, JD+ subclinical, and JD+ clinically infected cattle. MDMs were pre-treated 100 ng/ml 25(OH)D3 or 4 ng/ml 1,25(OH)2D3 and incubated 24 hrs with MAP at 10:1 multiplicity of infection (MOI). In vitro MAP infection upregulated pro-inflammatory (M1) CD80 and downregulated resolution/repair (M2) CD163. Vitamin D3 generally decreased CD80 and increased CD163 expression. Furthermore, early endosomal marker Rab5 was upregulated 140× across all stages of paratuberculosis infection following in vitro MAP infection; however, Rab5 was reduced in MAP-activated MDMs from JD+ subclinical and JD+ clinical cows compared to healthy controls. Rab7 expression decreased in control and clinical cows following MDM infection with MAP. Both forms of vitamin D3 reduced Rab5 expression in infected MDMs from JD- control cows, while 1,25(OH)2D3 decreased Rab7 expression in JD- and JD+ subclinical animals regardless of MAP infection in vitro. Vitamin D3 promoted phagocytosis in MDMs from JD- and JD+ clinical cows treated with either vitamin D3 analog. Results from this study show exogenous vitamin D3 influences macrophage M1/M2 polarization and Rab GTPase expression within MDM culture.
The evolving biology of Mycobacterium tuberculosis drug resistance
Authors: Jones Richard M. , Adams Kristin N. , Eldesouky Hassan E. , Sherman David R.
Published: October 2022

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb) is an ancient disease that has remained a leading cause of infectious death. Mtb has evolved drug resistance to every antibiotic regimen ever introduced, greatly complicating treatment, lowering rates of cure and menacing TB control in parts of the world. As technology has advanced, our understanding of antimicrobial resistance has improved, and our models of the phenomenon have evolved. In this review, we focus on recent research progress that supports an updated model for the evolution of drug resistance in Mtb. We highlight the contribution of drug tolerance on the path to resistance, and the influence of heterogeneity on tolerance. Resistance is likely to remain an issue for as long as drugs are needed to treat TB. However, with technology driving new insights and careful management of newly developed resources, antimicrobial resistance need not continue to threaten global progress against TB, as it has done for decades.
Evolutionary dynamics inform management interventions of a hanging garden obligate, Carex specuicola
Authors: Chapin Kenneth James , Jones Matthew R. , Winkler Daniel E. , Rink Glenn , Massatti Rob
Published: October 2022

Uncovering the historical and contemporary processes shaping rare species with complex distributions is of growing importance due to threats such as habitat destruction and climate change. Species restricted to specialized, patchy habitat may persist by virtue of life history characteristics facilitating ongoing gene flow and dispersal, but they could also reflect the remnants of formerly widespread, suitable habitat that existed during past climate regimes. If formerly widespread species did not rely upon traits facilitating high dispersibility to persist, contemporary populations could be at high risk of extirpation or extinction. Fortunately, genomic investigations provide an opportunity to illuminate such alternative scenarios while simultaneously offering guidance for future management interventions. Herein, we test the role of these mechanisms in shaping patterns of genomic diversity and differentiation across a highly restricted and rare ecosystem: desert hanging gardens. We focus on Carex specuicola (Cyperaceae), a hanging garden obligate narrowly distributed in the Four Corners region of the southwestern United States that is listed as Threatened under the United States Endangered Species Act. Population structure and diversity analyses reveal that hanging garden populations are shaped by strong genetic drift, but that individuals in gardens are occasionally more closely related to individuals at other gardens than to individuals within the same garden. Similarly, gardens separated by long geographic distances may contain individuals that are more closely related compared to individuals in gardens separated by short geographic distances. Demographic modeling supports historical gene flow between some contemporary garden pairs, which is corroborated by low estimates of inbreeding coefficients and recent divergence times. As such, multiple lines of evidence support dispersal and gene flow across C. specuicola populations at both small and large spatial scales, indicating that even if C. specuicola was formerly more widespread, it may be well suited to persist in hanging gardens so long as suitable habitat remains available. Analyses like those demonstrated herein may be broadly applicable for understanding the short- and long-term evolutionary processes influencing rare species, and especially those having complex distributions across heterogeneous landscapes.
Expression of connexin 43 protein in cardiomyocytes of heart failure mouse model
Authors: Liu Shaoyan , Lan Yang , Zhao Yun , Zhang Qianyu , Lin Tzuchun , Lin Kaibin , Guo Junjie , Yan Yan
Published: October 2022

Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, and is associated with a poor prognosis. One of the primary causes of HF is aortic valve disease, manifested by progressive aortic valve stenosis (AVS), resulting in increased left ventricular load, ventricular hypertrophy, ultimately ventricular dysfunction, and HF. Early assessment of the degree of cardiomyopathy and timely intervention is expected to improve patients’ cardiac function and delay or even avoid the occurrence of HF. The Wnt signaling pathway is mainly involved in regulating myocardial insufficiency after valve stenosis. Connexin 43 protein (Cx43) is an essential target of Wnt signaling pathway that forms gap junction (GJ) structures and is widely distributed in various organs and tissues, especially in the heart. The distribution and transformation of Cx43 among cardiac cells are crucial for the development of HF. To specifically label Cx43 in vivo, we established a new Cx43-BFP-GFP mouse model with two loxp sites on both sides of the tag BFP-polyA box, which can be removed by Cre recombination. This double-reporter line endowed us with a powerful genetic tool for determining the area, spatial distribution, and functional status of Cx43. It also indicated changes in electrical conduction between cells in a steady or diseased state.
Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease
Authors: Feugray Guillaume , Kasonga Fiston , Grall Maximilien , Dumesnil Cécile , Benhamou Ygal , Brunel Valery , Le Cam Duchez Véronique , Lahary Agnès , Billoir Paul
Published: October 2022

Introduction

Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder. The main consequence is synthesis of hemoglobin S leading to chronic hemolysis associated with morbidity. The aim of this study was to investigate Thrombin Generation Assay (TGA) to assess hypercoagulability in SCD and TGA parameters as biomarkers of vaso-occlusive crisis (VOC) risk and hospitalization within 1 year.

Materials and methods

We performed TGA in platelet poor plasma (PPP) with 1 pM of tissue factor and 4 μM of phospholipid-standardized concentration, in duplicate for patients and controls. We measured thrombomodulin (TM), soluble endothelial Protein C Receptor and Tissue Factor Pathway Inhibitor (TFPI).

Results

A total of 113 adult patients with SCD, 83 at steady state and 30 during VOC, and 25 healthy controls matched on age and gender were included. Among the 83 patients at steady state, (36 S/S-1 S/β0, 20 S/Sα3.7, and 19 S/C-7 S/β+) 28 developed a VOC within 1 year (median: 4 months [2.25–6]). We observed an increase of peak and velocity associated with a shortening of lagtime and time to peak (TTP) and no difference of endogenous thrombin potential (ETP) in patients compared to controls. TFPI (p < 0.001) and TM (p = 0.006) were significantly decreased. TGA confirmed hypercoagulability in all SCD genotypes and clinical status. The association of ETP > 1,207 nM.min and peak >228.5 nM presented a sensitivity of 73.5% and a specificity of 93.9% to predict VOC development within 1 year.

Conclusion

We have demonstrated a hypercoagulable state in SCD associated with chronic hemolysis. These preliminary findings suggest that TGA parameters, as ETP and peak, could be used to predict VOC development within 1 year.
Electrocardiogram abnormalities and prognosis in COVID-19
Authors: Chevrot Gabriel , Hauguel-Moreau Marie , Pépin Marion , Vieillard-Baron Antoine , Lot Anne-Sophie , Ouadahi Mounir , Hergault Hélène , Aïdan Vincent , Greffe Ségolène , Costantini Adrien , Dubourg Olivier , Beaune Sébastien , Mansencal Nicolas
Published: October 2022

Background

COVID-19 is a major pandemic with potential cardiovascular complications. Few studies have focused on electrocardiogram (ECG) modifications in COVID-19 patients.

Method and results

We reviewed from our database all patients referred to our hospital for COVID-19 between January 1st, 2020, and December 31st, 2020: 669 patients were included and 98 patients died from COVID-19 (14.6%). We systematically analyzed ECG at admission and during hospitalization if available. ECG was abnormal at admission in 478 patients (71.4%) and was more frequently abnormal in patients who did not survive (88.8 vs. 68.5%, p < 0.001). The most common ECG abnormalities associated with death were left anterior fascicular block (39.8 vs. 20.0% among alive patients, p < 0.001), left and right bundle branch blocks (p = 0.002 and p = 0.02, respectively), S1Q3 pattern (14.3 vs. 6.0%, p = 0.006). In multivariate analysis, at admission, the presence of left bundle branch block remained statistically related to death [OR = 3.82, 95% confidence interval (CI): 1.52–9.28, p < 0.01], as well as S1Q3 pattern (OR = 3.17, 95% CI: 1.38–7.03, p < 0.01) and repolarization abnormalities (OR = 2.41, 95% CI: 1.40–4.14, p < 0.01).

On ECG performed during hospitalization, the occurrence of new repolarization abnormality was significantly related to death (OR = 2.72, 95% CI: 1.14–6.54, p = 0.02), as well as a new S1Q3 pattern (OR = 13.23, 95% CI: 1.49–286.56, p = 0.03) and new supraventricular arrhythmia (OR = 3.8, 95% CI: 1.11–13.35, p = 0.03).

Conclusion

The presence of abnormal ECG during COVID-19 is frequent. Physicians should be aware of the usefulness of ECG for risk stratification during COVID-19.
Recovering groundwater for wetlands from an anthropogenic aquifer
Authors: Hatch Christine E. , Ito Erika T.
Published: October 2022

Freshwater wetlands are groundwater-dependent ecosystems that require groundwater for saturation, for wetland plants and creatures, for maintenance of wetland soils, and thermal buffering. With worldwide wetland area in decline for decades if not centuries, finding and restoring wetlands provides enormous ecosystem and public benefits, yet so often these projects fail to yield self-sustaining wetland ecosystems. One reason is that restored wetlands are often built in places that are neither wet enough nor possess the underlying geology to sustain them, and they dry out or require continual (expensive!) water inputs. Massachusetts is making the best of a challenging situation for the declining cranberry farming industry: while competition from less expensive land and more productive varietals shifts cranberry production to other locations, everything under historic cranberry farms is ripe for resilient wetland restoration projects. These low-lying water-rich areas are underlain by glacial geology (peats and clays) that are ideal for holding water, they possess historic seed banks of wetland plants and large accumulations of organic and hydric soils, and are currently sought-after by a statewide restoration program, for which these results provide critical information for restoration design, enabling practitioners to maximize the capture and residence time of groundwater inputs to sustain the future wetland. In this paper, we investigate the human legacy of cranberry farming on the surface of a wetland as it has created a unique hydrogeologic unit: the anthropogenic aquifer. Water moves through an anthropogenically constructed aquifer in specific and predictable ways that were engineered to favor a monoculture of cranberry plants on the surface of what once was a peatland. In order to restore this landscape to a functioning freshwater wetland, every property of the anthropogenic aquifer must be reversed. We detail observational, thermal, hydrologic, geologic and isotopic evidence for the location of groundwater inflows to Foothills Preserve in southeastern Massachusetts. The specific properties of the Anthropogenic aquifer, and the location and magnitude of groundwater discharge at this location provide crucial information for practitioners when designing plans for a self-sustaining, resilient restored freshwater wetland on this and future sites.
Effects of perioperative glycemic indicators on outcomes of endovascular treatment for vertebrobasilar artery occlusion
Authors: Gu Mengmeng , Fan Jin , Xu Pengfei , Xiao Lulu , Wang Jinjing , Li Min , Liu Chaolai , Luo Genpei , Cai Qiankun , Liu Dezhi , Ye Lichao , Zhou Junshan , Sun Wen
Published: October 2022

Objective

Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT.

Methods

We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM).

Results

A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history.

Conclusions

Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.
Metformin and risk of gingival/periodontal diseases in diabetes patients: A retrospective cohort study
Authors: Tseng Chin-Hsiao
Published: October 2022

Aim

To compare the risk of gingival and periodontal diseases (GPD) between ever users and never users of metformin in patients with type 2 diabetes mellitus.

Methods

The Taiwan’s National Health Insurance database was used to enroll 423,949 patients with new onset diabetes mellitus from 1999 to 2005. After excluding ineligible patients, 60,309 ever users and 5578 never users were followed up for the incidence of GPD from January 1, 2006 until December 31, 2011. Propensity score-weighted hazard ratios were estimated by Cox regression.

Results

GPD was newly diagnosed in 18,528 ever users (incidence: 7746.51 per 100,000 person-years) and 2283 never users (incidence: 12158.59 per 100,000 person-years). The hazard ratio that compared ever users to never users was 0.627 (95% confidence interval: 0.600-0.655). When metformin use was categorized by tertiles of cumulative duration and cumulative dose, the risk significantly reduced in a dose-response pattern when the cumulative duration reached approximately 2 years or the cumulative dose reached 670 grams. Analyses on the tertiles of defined daily dose of metformin showed that the reduction of GPD risk could be seen in all three subgroups but the benefit would be greater when the daily dose increased.

Conclusion

Long-term use of metformin is associated with a significantly reduced risk of GPD.
Association between perfluoroalkyl substances concentration and bone mineral density in the US adolescents aged 12-19 years in NHANES 2005-2010
Authors: Xiong Xianmei , Chen Baihang , Wang Zhongqing , Ma Liqiong , Li Shijie , Gao Yijia
Published: October 2022

Background

Reports on the association of perfluoroalkyl substances (PFASs) exposure with adolescent bone health are scarce, and studies have primarily targeted maternal serum.

Objective

We evaluated the relationship between autologous serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) levels and bone mineral density (BMD) in adolescents.

Methods

We analyzed data from 1228 adolescents aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 and used multiple regression analysis to identify the relationship between serum PFOA, PFOS, PFHxS, and PFNA concentrations and total femur, femoral neck, and lumbar spine BMD, in addition to multiple stratified subgroup analyses.

Results

The mean age of participants was 15 years, males had higher serum PFAS concentrations than females. The results of multiple regression analysis showed that the natural log(ln)-transformed serum PFOA, PFOS, and PFNA concentrations were negatively correlated with total femur, femoral neck, and lumbar spine BMD (all p < 0.05), and ln-PFHxS was positively correlated with total femur and femoral neck BMD (all p< 0.05). In males, ln-PFOA was negatively associated with total femur and lumbar spine BMD (all p< 0.05), ln-PFOS was associated with the reduced total femur, femoral neck, and lumbar spine BMD (all p< 0.05), while ln-PFHxS and ln-PFNA were not observed to correlate with BMD at these three sites. In females, both ln-PFOA and ln-PFOS were negatively correlated with total femur and lumbar spine BMD (all p< 0.05), ln-PFHxS is associated with the increased total femur and femoral neck BMD (all p< 0.05), and ln-PFNA was negatively correlated with total femur and femoral neck BMD (all p< 0.05), most of the associations were confined to females. The associations of ln-PFOS with femoral neck BMD and ln-PFNA with total femur BMD were more significant in those who were overweight/obese and had anemia, respectively (all p for interaction < 0.05).

Conclusions

In this representative sample of US adolescents aged 12-19 years, certain PFAS were associated with lower bone mineral density, and most of the associations were confined to females. The negative effect of PFAS on BMD is more pronounced in those who are overweight/obese and have anemia. However, further studies are needed to confirm this finding.
From hormone replacement therapy to regenerative scaffolds: A review of current and novel primary hypothyroidism therapeutics
Authors: Heim Maria , Nixon Ian J. , Emmerson Elaine , Callanan Anthony
Published: October 2022

Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation. Multiple of these scaffolds have successfully restored an athyroid phenotype in vivo. However, further work is needed until clinical translation can be achieved. This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional in vivo experimentation providing data on safety and efficacy of these implants.
Curve matching to predict growth in patients receiving growth hormone therapy: An interpretable & explainable method
Authors: van Dommelen Paula , Arnaud Lilian , Koledova Ekaterina
Published: October 2022

Curve matching may be used to predict growth outcomes using data of patients whose growth curves resemble those of a new patient with growth hormone deficiency (GHD) and those born small for gestational age (SGA). We aimed to investigate the validity of curve matching to predict growth in patients with GHD and those born SGA receiving recombinant human growth hormone (r-hGH). Height data collected between 0–48 months of treatment were extracted from the easypod™ connect ecosystem and the easypod™ connect observational study. Selected patients with height standard deviation scores (HSDS) [-4, <-1] and age [3, <16y] at start were included. The ‘Matching Database’ consisted of patients’ monthly HSDS obtained by the broken stick method and imputation. Standard deviation (SD) was obtained from the observed minus the predicted HSDS (error) based on matched patients within the ‘Matching Database’. Data were available for 3,213 patients in the ‘Matching Database’, and 2,472 patients with 16,624 HSDS measurements in the observed database. When ≥2 HSDS measurements were available, the error SD for a one-year prediction was approximately 0.2, which corresponds to 1.1 cm, 1.3 cm, and 1.5 cm at 7, 11, and 15 years of age, respectively. Indication and age at treatment start (<11 vs ≥11 years) had a small impact on the error SD, with patients born SGA and patients aged <11 years at treatment start generally having slightly lower values. We conclude that curve matching is a simple and valid technique for predicting growth in patients with GHD and those born SGA.
MHD Eyring–Powell nanofluid flow across a wedge with convective and thermal radiation
Authors: Raju CH. Narasimha , Reddy C. Srinivas , Alyami Maryam Ahmed , Eldin Sayed M , Adnan  , Asogwa Kanayo Kenneth , Pushpa D. , Dharmaiah V.
Published: October 2022

In this research, a theoretical investigation into the heat transport characteristics of an Eyring–Powell nanomaterial boundary layer flow on a wedge surface with passively controlled nanoparticles is carried out. In this model, thermal convective boundary conditions, thermal radiation, heat production, and absorption are also studied. The non-Newtonian Eyring–Powell fluid’s features are predicted using the model under consideration. The Buongiorno model is used to study how a temperature gradient affects thermophoresis and how nanoparticles affect the Brownian motion. The prevailing nonlinear boundary layer equations are derived and then renewed in an ordinary differential boundary value problem (ODBVP) by substituting apt similarity transformations. The acquired nonlinear ODBVP is then resolved using the bvp4c method to explore the fields of nanofluid velocity, nanofluid temperature, and nanoparticle concentration. A mathematical examination of the surface drag force coefficients and Nusselt number is carried out using various physical parameters. The Eyring–Powell fluid parameter (K1) reduces the thickness of the momentum boundary layer thickness. The thermophoresis aspect (Nt) enhances the thermal field and solutal field. The Nusselt number (NuRex−0.5) reduces the need for a stronger internal heat source mechanism.
Hearing loss and risk of depressive symptoms in older adults in the Health ABC study
Authors: Powell Danielle S. , Betz Joshua F. , Yaffe Kristine , Kritchevsky Stephen , Strotmeyer Elsa , Simonsick Eleanor M. , Rubin Susan , Houston Denise K. , Pratt Sheila R. , Purchase Helzner Elizabeth , Brewster Katharine K. , Lin Frank R. , Gross Alden L. , Deal Jennifer A.
Published: October 2022

Objective

Hearing loss (HL) is highly prevalent among older adults and may lead to increased risk of depressive symptoms. In both cross-sectional and longitudinal analysis, we quantified the association between HL and depressive symptoms, incorporating the variable nature of depressive symptoms and characterizing by race and gender.

Methods

Data were from the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Study Depression Scale short form (CES-D 10), defined as CES-D 10 score ≥10 or treatment for depression. Hearing was defined via four-frequency pure-tone average (PTA) decibel hearing level (dB HL), categorized as normal hearing (PTA ≤25 dB HL), mild HL (PTA26-40 dB HL), and ≥moderate HL (PTA > 40 dB HL). Associations at baseline were quantified using logistic regression, incident depressive symptoms using Cox proportional hazard models, and change in depressive symptoms over time using growth mixture models and multinomial logistic regression.

Results

Among 2,089 older adults (1,082 women, 793 Black; mean age 74.0 SD: 2.8), moderate or greater HL was associated with greater odds of concurrent [Odds Ratio (OR):2.45, 95% CI:1.33, 4.51] and incident depressive symptoms [Hazard Ratio (HR):1.26, 95% CI:1.00, 1.58]. Three depressive symptom trajectory patterns were identified from growth mixture models: low, moderate increasing, and borderline high depressive symptom levels. Those with moderate or greater HL were more likely to be in the borderline high depressive-symptom trajectory class than the low trajectory class [Relative Risk Ratio (RRR):1.16, 95% CI:1.01, 1.32].

Conclusions

HL was associated with greater depressive symptoms. Although findings were not statistically significantly different by gender and race, estimates were generally stronger for women and Black participants. Investigation of psychosocial factors and amelioration by hearing aid use could have significant benefit for older adults' quality of life.
Stable isotopes elucidate body-size and seasonal fluctuations in the feeding strategies of planktivorous fishes across a semi-enclosed tropical embayment
Authors: Skinner Christina , Pei Yu-De , Morimoto Naoko , Miyajima Toshihiro , Wyatt Alex S. J.
Published: October 2022

Reef fish may switch feeding strategies due to fluctuations in resource availability or through ontogeny. A number of studies have explored these trophodynamics using carbon (δ13C) and nitrogen (δ15N) stable isotopes, but additional tracers such as sulfur isotopes (δ34S) show strong potential in systems, where δ13C and δ15N results are ambiguous. We tested the utility of adding δ34S to conventional δ13C and δ15N analysis to detect seasonal and body size changes in resource use of two planktivorous damselfish, Dascyllus reticulatus and Dascyllus trimaculatus across the Puerto Galera embayment in the Philippines. We analyzed stable isotope ratios (δ13C, δ15N, and δ34S) in multiple fish tissues (liver, eye, and muscle) to represent different dietary time frames. We then compared fish tissue isotopes against particulate organic matter (POM) (δ13C and δ15N) and POM suspension feeder (the tunicate Polycarpa aurata: δ13C, δ15N, and δ34S) across the same sites. There were size-based and seasonal differences in damselfish resource use, the latter of which was most pronounced in the fast-turnover liver. Small fish (<70 mm) demonstrated significant seasonality, appearing to switch their resource use between the rainy season and the dry season, while there was no seasonal variation in larger fish (>70 mm). This suggests that smaller fish across the embayment employ an opportunistic feeding strategy to take advantage of fluctuating resource availability, while larger fish exhibits more consistent resource use. Isotope ratios of tunicates and POM further confirmed strong seasonality in this system and a lack of a spatial isotopic gradient. δ15N did not seem to contribute to consumer resource use patterns, while by contrast, δ34S fluctuated significantly between sampling periods and was crucial for demonstrating seasonality in resource use. We recommend including δ34S when attempting to disentangle seasonal differences in resource use in aquatic food webs using stable isotopes.
A guidance of model selection for genomic prediction based on linear mixed models for complex traits
Authors: Duan Jiefang , Zhang Jiayu , Liu Long , Wen Yalu
Published: October 2022

Brain imaging outcomes are important for Alzheimer’s disease (AD) detection, and their prediction based on both genetic and demographic risk factors can facilitate the ongoing prevention and treatment of AD. Existing studies have identified numerous significantly AD-associated SNPs. However, how to make the best use of them for prediction analyses remains unknown. In this research, we first explored the relationship between genetic architecture and prediction accuracy of linear mixed models via visualizing the Manhattan plots generated based on the data obtained from the Wellcome Trust Case Control Consortium, and then constructed prediction models for eleven AD-related brain imaging outcomes using data from United Kingdom Biobank and Alzheimer’s Disease Neuroimaging Initiative studies. We found that the simple Manhattan plots can be informative for the selection of prediction models. For traits that do not exhibit any significant signals from the Manhattan plots, the simple genomic best linear unbiased prediction (gBLUP) model is recommended due to its robust and accurate prediction performance as well as its computational efficiency. For diseases and traits that show spiked signals on the Manhattan plots, the latent Dirichlet process regression is preferred, as it can flexibly accommodate both the oligogenic and omnigenic models. For the prediction of AD-related traits, the Manhattan plots suggest their polygenic nature, and gBLUP has achieved robust performance for all these traits. We found that for these AD-related traits, genetic factors themselves only explain a very small proportion of the heritability, and the well-known AD risk factors can substantially improve the prediction model.
The involvement of homeobox-C 4 in predicting prognosis and unraveling immune landscape across multiple cancers via integrated analysis
Authors: Xiao Junbo , Li Ying , Liu Yajun , Chen Yiqian , He Zixuan , Peng Shifang , Yin Yani
Published: October 2022

Background: There has been growing evidence that the aberrantly expressed Homeobox-C 4 (HOXC4) plays crucial roles in the development of some cancer types. However, it remains unclear as far as its expression patterns and prognostic significance are concerned, as is tumor immunity.

Methods: To investigate the expression levels and prognostic implications of HOXC4, multiple data sources were used in conjunction with quantitative real-time polymerase chain reaction (qRT-PCR) verification. Afterward, diverse immunological-related analyses, along with anti-cancer drug sensitivity, were performed in a number of cancer types. A further exploration of the underlying mechanisms of HOXC4 in tumorigenesis and immunity was carried out using the Gene Set Enrichment Analysis (GSEA) and the Gene Set Variation Analysis (GSVA).

Results: Based on extensive database mining, HOXC4 was ubiquitously expressed across 21 tumor cell lines and significantly higher than that of normal tissues in 21 tumor types. The outcome of survival analysis including overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS) and progression-free interval (PFI) revealed that upregulation of HOXC4 expression in several cancers was associated with worse prognosis. Additionally, HOXC4 was observed to correlate closely with colon adenocarcinoma (COAD), head and neck squamous cell carcinoma (HNSC), lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ), and thyroid carcinoma (THCA) in terms of tumor immune cells infiltration. As a result of our comprehensive pan-cancer study, we have identified a significant link between the expression of HOXC4 and the efficacy of immunotherapy-related treatments, together with anti-cancer drug sensitivity. As a final note, HOXC4 was found to modulate multiple signaling pathways involved in tumorigenesis and immunity.

Conclusion: HOXC4 has been implicated in our study for the first time as an oncogene in cancers with a poor prognosis, potentially laying the groundwork for promising clinical biomarkers and immunotherapy approaches.
A lactate-related LncRNA model for predicting prognosis, immune landscape and therapeutic response in breast cancer
Authors: Li Jia , Zhang Yinbin , Li Chaofan , Wu Huizi , Feng Cong , Wang Weiwei , Liu Xuan , Zhang Yu , Cai Yifan , Jia Yiwei , Qiao Hao , Wu Fei , Zhang Shuqun
Published: October 2022

Breast cancer (BC) has the highest incidence rate of all cancers globally, with high heterogeneity. Increasing evidence shows that lactate and long non-coding RNA (lncRNA) play a critical role in tumor occurrence, maintenance, therapeutic response, and immune microenvironment. We aimed to construct a lactate-related lncRNAs prognostic signature (LRLPS) for BC patients to predict prognosis, tumor microenvironment, and treatment responses. The BC data download from the Cancer Genome Atlas (TCGA) database was the entire cohort, and it was randomly assigned to the training and test cohorts at a 1:1 ratio. Difference analysis and Pearson correlation analysis identified 196 differentially expressed lactate-related lncRNAs (LRLs). The univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to construct the LRLPS, which consisted of 7 LRLs. Patients could be assigned into high-risk and low-risk groups based on the medium-risk sore in the training cohort. Then, we performed the Kaplan–Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. The results indicated that the prognosis prediction ability of the LRLPS was excellent, robust, and independent. Furthermore, a nomogram was constructed based on the LRLPS risk score and clinical factors to predict the 3-, 5-, and 10-year survival probability. The GO/KEGG and GSEA indicated that immune-related pathways differed between the two-risk group. CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore (IPS) showed that low-risk patients had higher levels of immune infiltration and better immunotherapeutic response. The pRRophetic and CellMiner databases indicated that many common chemotherapeutic drugs were more effective for low-risk patients. In conclusion, we developed a novel LRLPS for BC that could predict the prognosis, immune landscape, and treatment response.
EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma
Authors: Liu Jing , Liu Tongyu , Zhang Chuanhao , He Jiabei , Zhou Dong , Wang Zhe , Wang Ruoyu
Published: October 2022

Background: Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis. It is urgent to find effective biomarkers. Eukaryotic Translation Initiation Factor 2 Subunit Beta (EIF2S2) is a subunit of heterotrimeric G protein EIF2, and its function is still unclear. We studied the role of EIF2S2 in the malignant progression of liver cancer and its relationship with immune infiltration.

Methods: Download the RNA expression and clinical information of EIF2S2 from the Cancer Genome Atlas (TCGA) database, analyze the relationship between the expression of EIF2S2 and the prognosis and clinicopathological characteristics of HCC, analyze the differential genes by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and tumor related immune infiltrating cells. The Protein expression level of EIF2S2 was obtained from Human Protein Atlas (HPA) databases. The relationship between EIF2S2 expression and immune infiltrates in HCC was analyzed on TIMER 2.0. The data processing analysis based on R language. Drug Sensitivity data from Genomics of Drug Sensitivity in Cancer (GDSC).

Results: EIF2S2 is highly expressed in HCC patients and is associated with poor prognosis. The expression of EIF2S2 was also correlated with age, clinical stage and pathological grade. Univariate and multivariate COX regression analysis showed that EIF2S2 was an independent risk factor for survival. The receiver operating characteristic (ROC) curve of EIF2S2 also confirmed the diagnostic value of EIF2S2 in HCC patients. Through GO and KEGG enrichment analysis, EIF2S2 expression was found to be closely related to some immune pathways. The expression of EIF2S2 was correlated with memory B cell, plasma B cell, CD8+ T cell, CD4+ resting memory T cell and the expression of some immune checkpoints, such as PDCD1, TIGIT and CTLA-4. It is also more sensitive to paclitaxel, sunitinib and other drugs.

Conclusion: This study shows that EIF2S2 can be used as a prognostic factor for HCC, which is closely related to immune infiltration and immune checkpoints, and may play a potential regulatory role in predicting drug sensitivity.
Development and function of regulatory innate lymphoid cells
Authors: Thomas Christopher M. , Peebles R. Stokes
Published: October 2022

Innate lymphoid cells (ILCs) are a critical element of the innate immune system and are potent producers of pro-inflammatory cytokines. Recently, however, the production of the anti-inflammatory cytokine IL-10 has been observed in all ILC subtypes (ILC1s, ILC2s, and ILC3s) suggesting their ability to adopt a regulatory phenotype that serves to maintain lung and gut homeostasis. Other studies advocate a potential therapeutic role of these IL-10-expressing ILCs in allergic diseases such as asthma, colitis, and pancreatic islet allograft rejection. Herein, we review IL-10 producing ILCs, discussing their development, function, regulation, and immunotherapeutic potential through suppressing harmful inflammatory responses. Furthermore, we address inconsistencies in the literature regarding these regulatory IL-10 producing ILCs, as well as directions for future research.
Comparative analysis of the repertoire of insulin-reactive B cells in type 1 diabetes-prone and resistant mice
Authors: Banach Maureen , Harley Isaac T. W. , Getahun Andrew , Cambier John C.
Published: October 2022

Seropositivity for autoantibodies against multiple islet antigens is associated with development of autoimmune type 1 diabetes (T1D), suggesting a role for B cells in disease. The importance of B cells in T1D is indicated by the effectiveness of B cell-therapies in mouse models and patients. B cells contribute to T1D by presenting islet antigens, including insulin, to diabetogenic T cells that kill pancreatic beta cells. The role of B cell receptor (BCR) affinity in T1D development is unclear. Here, we employed single cell RNA sequencing to define the relationship between BCR affinity for insulin and B cell phenotype during disease development. We utilized immunoglobulin (Ig) heavy chain (VH125) mouse models in which high-affinity insulin-reactive B cells (IBCs) were previously shown to be anergic in diabetes-resistant VH125.C57BL/6-H2g7 and activated in VH125. NOD mice developing disease. Here, high-affinity IBCs were found in the spleen of prediabetic VH125. NOD mice and exhibited marginal zone or follicular phenotypes. Ig light chains expressed by these B cells are unmutated and biased toward Vκ4-74 and Vκ4-57 usage. Receptors expressed by anergic high-affinity IBCs of diabetes-resistant VH125.C57BL/6-H2g7 are also unmutated; however, in this genetic background light chains are polymorphic relative to those of NOD. Light chains derived from NOD and C57BL/6-H2g7 genetic backgrounds conferred divergent kinetics of binding to insulin when paired with the VH125 heavy chain. These findings suggest that relaxation of tolerance mechanisms in the NOD mouse leads to accumulation and partial activation of B cells expressing germline encoded high-affinity BCRs that support development of autoimmunity.
Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma
Authors: Zhang Wenqi , Huang Chen , Liu Ruixia , Zhang Huichao , Li Weijing , Yin Shaoning , Wang Lianjing , Liu Wei , Liu Lihong
Published: October 2022

Current therapeutic strategies for central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) are extremely limited. Secondary central nervous system lymphoma (SCNSL) also shows a grave prognosis and high mortality. This report describes a young female patient with DLBCL and CNS relapse who received low-dose CD19-directed chimeric antigen receptor T (CAR-T) cell therapy followed with Bruton’s tyrosine kinase inhibitor and programmed cell death protein 1 antibody after several lines of chemotherapy. However, limited reports on CAR-T cell therapy are applied for SCNSL, particularly those in combination with targeted agents. The current treatment combination for this case provides a new regimen for CNS relapse from DLBCL.

Clinical Trial Registration

ClinicalTrials.gov number, NCT04666168.
Immune and inflammatory mechanisms of abdominal aortic aneurysm
Authors: Márquez-Sánchez Ana Cristina , Koltsova Ekaterina K.
Published: October 2022

Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. Immune-mediated infiltration and a destruction of the aortic wall during AAA development plays significant role in the pathogenesis of this disease. While various immune cells had been found in AAA, the mechanisms of their activation and function are still far from being understood. A better understanding of mechanisms regulating the development of aberrant immune cell activation in AAA is essential for the development of novel preventive and therapeutic approaches. In this review we summarize current knowledge about the role of immune cells in AAA and discuss how pathogenic immune cell activation is regulated in this disease.
Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis
Authors: Lin Yi , Zhao Ying-Jie , Zhang Hai-Lin , Hao Wen-Juan , Zhu Ren-Di , Wang Yan , Hu Wei , Zhou Ren-Peng
Published: October 2022

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation. Immune dysfunction is an essential mechanism in the pathogenesis of RA and directly linked to synovial inflammation and cartilage/bone destruction. Intermediate conductance Ca2+-activated K+ channel (KCa3.1) is considered a significant regulator of proliferation, differentiation, and migration of immune cells by mediating Ca2+ signal transduction. Earlier studies have demonstrated abnormal activation of KCa3.1 in the peripheral blood and articular synovium of RA patients. Moreover, knockout of KCa3.1 reduced the severity of synovial inflammation and cartilage damage to a significant extent in a mouse collagen antibody-induced arthritis (CAIA) model. Accumulating evidence implicates KCa3.1 as a potential therapeutic target for RA. Here, we provide an overview of the KCa3.1 channel and its pharmacological properties, discuss the significance of KCa3.1 in immune cells and feasibility as a drug target for modulating the immune balance, and highlight its emerging role in pathological progression of RA.