bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway
Authors: Krause Robert , Snyman Jumari , Shi-Hsia Hwa , Muema Daniel , Karim Farina , Ganga Yashica , Ngoepe Abigail , Zungu Yenzekile , Gazy Inbal , Bernstein Mallory , Khan Khadija , Mazibuko Matilda , Mthabela Ntombifuthi , Ramjit Dirhona ,   COMMIT-KZN Team, Limbo Oliver , Jardine Joseph , Sok Devin , Wilson Ian A , Hanekom Willem , Sigal Alex , Kløverpris Henrik , Ndung'u Thumbi , Leslie Alasdair
Published: October 2022

Background:

HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections.

Methods:

We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features.

Results:

This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal centre (GC) activity, homing capacity, and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naïve B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2-specific EF response in PLWH was confirmed using viral spike and RBD bait proteins.

Conclusions:

Despite similar disease severity, these trends were highest in participants with uncontrolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge.

Funding:

This work was supported by a grant from the Wellcome Trust to the Africa Health Research Institute (Wellcome Trust Strategic Core Award [grant number 201433/Z/16/Z]). Additional funding was received from the South African Department of Science and Innovation through the National Research Foundation (South African Research Chairs Initiative [grant number 64809]), and the Victor Daitz Foundation.
Coding of latent variables in sensory, parietal, and frontal cortices during closed-loop virtual navigation
Authors: Noel Jean-Paul , Balzani Edoardo , Avila Eric , Lakshminarasimhan Kaushik J , Bruni Stefania , Alefantis Panos , Savin Cristina , Angelaki Dora E
Published: October 2022

We do not understand how neural nodes operate and coordinate within the recurrent action-perception loops that characterize naturalistic self-environment interactions. Here, we record single-unit spiking activity and local field potentials (LFPs) simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and dorsolateral prefrontal cortex (dlPFC) as monkeys navigate in virtual reality to ‘catch fireflies’. This task requires animals to actively sample from a closed-loop virtual environment while concurrently computing continuous latent variables: (i) the distance and angle travelled (i.e., path integration) and (ii) the distance and angle to a memorized firefly location (i.e., a hidden spatial goal). We observed a patterned mixed selectivity, with the prefrontal cortex most prominently coding for latent variables, parietal cortex coding for sensorimotor variables, and MSTd most often coding for eye movements. However, even the traditionally considered sensory area (i.e., MSTd) tracked latent variables, demonstrating path integration and vector coding of hidden spatial goals. Further, global encoding profiles and unit-to-unit coupling (i.e., noise correlations) suggested a functional subnetwork composed by MSTd and dlPFC, and not between these and 7a, as anatomy would suggest. We show that the greater the unit-to-unit coupling between MSTd and dlPFC, the more the animals’ gaze position was indicative of the ongoing location of the hidden spatial goal. We suggest this MSTd-dlPFC subnetwork reflects the monkeys’ natural and adaptive task strategy wherein they continuously gaze toward the location of the (invisible) target. Together, these results highlight the distributed nature of neural coding during closed action-perception loops and suggest that fine-grain functional subnetworks may be dynamically established to subserve (embodied) task strategies.
Descending neuron population dynamics during odor-evoked and spontaneous limb-dependent behaviors
Authors: Aymanns Florian , Chen Chin-Lin , Ramdya Pavan
Published: October 2022

Deciphering how the brain regulates motor circuits to control complex behaviors is an important, long-standing challenge in neuroscience. In the fly, Drosophila melanogaster, this is coordinated by a population of ~ 1100 descending neurons (DNs). Activating only a few DNs is known to be sufficient to drive complex behaviors like walking and grooming. However, what additional role the larger population of DNs plays during natural behaviors remains largely unknown. For example, they may modulate core behavioral commands or comprise parallel pathways that are engaged depending on sensory context. We evaluated these possibilities by recording populations of nearly 100 DNs in individual tethered flies while they generated limb-dependent behaviors, including walking and grooming. We found that the largest fraction of recorded DNs encode walking while fewer are active during head grooming and resting. A large fraction of walk-encoding DNs encode turning and far fewer weakly encode speed. Although odor context does not determine which behavior-encoding DNs are recruited, a few DNs encode odors rather than behaviors. Lastly, we illustrate how one can identify individual neurons from DN population recordings by using their spatial, functional, and morphological properties. These results set the stage for a comprehensive, population-level understanding of how the brain’s descending signals regulate complex motor actions.
Strip thickness prediction method based on improved border collie optimizing LSTM
Authors: Sun Lijie , Zeng Lin , Zhou Hongjuan , Zhang Lei
Published: October 2022

Background

The thickness accuracy of strip is an important indicator to measure the quality of strip, and the control of the thickness accuracy of strip is the key for the high-quality strip products in the rolling industry.

Methods

A thickness prediction method of strip based on Long Short-Term Memory (LSTM) optimized by improved border collie optimization (IBCO) algorithm is proposed. First, chaotic mapping and dynamic weighting strategy are introduced into IBCO to overcome the shortcomings of uneven initial population distribution and inaccurate optimization states of some individuals in Border Collie Optimization (BCO). Second, Long Short-Term Memory (LSTM) which can effectively deal with time series data and alleviate long-term dependencies is adopted. What’s more, IBCO is utilized to optimize parameters to mitigate the influence of hyperparameters such as the number of hidden neurons and learning rate on the prediction accuracy of LSTM, so IBCO-LSTM is established.

Results

The experiments are carried out on the measured strip data, which proves the excellent prediction performance of IBCO-LSTM. The experiments are carried out on the actual strip data, which prove that IBCO-LSTM has excellent capability of prediction.
GPX2 predicts recurrence-free survival and triggers the Wnt/β-catenin/EMT pathway in prostate cancer
Authors: Yang Ming , Zhu Xudong , Shen Yang , He Qi , Qin Yuan , Shao Yiqun , Yuan Lin , Ye Hesong
Published: October 2022

Objective

This study aimed to establish a prognostic model related to prostate cancer (PCa) recurrence-free survival (RFS) and identify biomarkers.

Methods

The RFS prognostic model and key genes associated with PCa were established using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression from the Cancer Genome Atlas (TCGA)-PRAD and the Gene Expression Omnibus (GEO) GSE46602 datasets. The weighted gene co-expression network (WGCNA) was used to analyze the obtained key modules and genes, and gene set enrichment analysis (GSEA) was performed. The phenotype and mechanism were verified in vitro.

Results

A total of 18 genes were obtained by LASSO regression, and an RFS model was established and verified (TCGA, AUC: 0.774; GSE70768, AUC: 0.759). Three key genes were obtained using multivariate Cox regression. WGCNA analysis obtained the blue module closely related to the Gleason score (cor = –0.22, P = 3.3e − 05) and the unique gene glutathione peroxidase 2 (GPX2). Immunohistochemical analysis showed that the expression of GPX2 was significantly higher in patients with PCa than in patients with benign prostatic hyperplasia (P < 0.05), but there was no significant correlation with the Gleason score (GSE46602 and GSE6919 verified), which was also verified in the GSE46602 and GSE6919 datasets. The GSEA results showed that GPX2 expression was mainly related to the epithelial–mesenchymal transition (EMT) and Wnt pathways. Additionally, GPX2 expression significantly correlated with eight kinds of immune cells. In human PCa cell lines LNCaP and 22RV1, si-GPX2 inhibited proliferation and invasion, and induced apoptosis when compared with si-NC. The protein expression of Wnt3a, glycogen synthase kinase 3β (GSK3β), phosphorylated (p)-GSK3β, β-catenin, p-β-catenin, c-myc, cyclin D1, and vimentin decreased; the expression of E-cadherin increased; and the results for over-GPX2 were opposite to those for over-NC. The protein expression of GPX2 decreased, and β-catenin was unchanged in the si-GPX2+ SKL2001 group compared with the si-NC group.

Conclusion

We successfully constructed the PCa RFS prognostic model, obtained RFS-related biomarker GPX2, and found that GPX2 regulated PCa progression and triggered Wnt/β-catenin/EMT pathway molecular changes.
Changes in ecological conditions may influence intraguild competition: inferring interaction patterns of snow leopard with co-predators
Authors: Pal Ranjana , Panwar Anshu , Goyal Surendra P. , Sathyakumar Sambandam
Published: October 2022

Background

Large-scale changes in habitat conditions due to human modifications and climate change require management practices to consider how species communities can alter amidst these changes. Understanding species interactions across the gradient of space, anthropogenic pressure, and season provide the opportunity to anticipate possible dynamics in the changing scenarios. We studied the interspecific interactions of carnivore species in a high-altitude ecosystem over seasonal (summer and winter) and resource gradients (livestock grazing) to assess the impact of changing abiotic and biotic settings on coexistence.

Methods

The study was conducted in the Upper Bhagirathi basin, Western Himalaya, India. We analyzed around 4 years of camera trap monitoring data to understand seasonal spatial and temporal interactions of the snow leopard with common leopard and woolly wolf were assessed in the greater and trans-Himalayan habitats, respectively. We used two species occupancy models to assess spatial interactions, and circadian activity patterns were used to assess seasonal temporal overlap amongst carnivores. In addition, we examined scats to understand the commonalities in prey selection.

Results

The result showed that although snow leopard and wolves depend on the same limited prey species and show high temporal overlap, habitat heterogeneity and differential habitat use facilitate co-occurrence between these two predators. Snow leopard and common leopard were spatially independent in the summer. Conversely, the common leopard negatively influences the space use of snow leopard in the winter. Limited prey resources (lack of livestock), restricted space (due to snow cover), and similar activity patterns in winter might result in strong competition, causing these species to avoid each other on a spatial scale. The study showed that in addition to species traits and size, ecological settings also play a significant role in deciding the intensity of competition between large carnivores. Climate change and habitat shifts are predicted to increase the spatial overlap between snow leopard and co-predators in the future. In such scenarios, wolves and snow leopards may coexist in a topographically diverse environment, provided sufficient prey are available. However, shifts in tree line might lead to severe competition between common leopards and snow leopards, which could be detrimental to the latter. Further monitoring of resource use across abiotic and biotic environments may improve our understanding of how changing ecological conditions can affect resource partitioning between snow leopards and predators.
La dimensión teológica de la crisis de los abusos. Reflexiones desde la antropología teológica
Authors:   Facultad de Teología. Pontificia Universidad Católica de Chile, Guridi Román
Published: October 2022

Esta contribución propone una reflexión que resalta la dimensión teológica de la crisis de los abusos en contextos eclesiales, junto con algunas consideraciones que deben ser tenidas en cuenta para no caer en asociaciones simplistas o en atribuciones causales difíciles de sostener. Por otra parte, propone algunos nudos problemáticos relacionados con la antropología teológica que merecen ser profundizados para hacerse cargo de la crisis eclesial de los abusos desde todos sus ámbitos: a. la reflexión sobre la polaridad don/límite que subyace a la comprensión teológica del poder humano; b. la conceptualización del excepcionalismo humano y sus implicancias; y, c. el déficit teológico en la consideración de la niñez.
Tumour Necrotic Factor Alpha level and Some Biochemical Parameters as a Measure of Health Risks Due to Exposure to Liquefied Petroleum Gas on Vendors in Calabar, Nigeria
Authors: Sambo Abara, Ukeme , Chinyere Nsonwu-Anyanwu, Augusta , Sunday Etukudoh, Nkeruwem , Henrietta Etukudo, Maisie , Denkok Yohanna , Obiora Ejinaka, Reginald , Ukeme Abara, Esitmbom , Larrycarr Nwapi, Lucy , Paul Udobong, Caroline
Published: October 2022

Background: The human body is constantly exposed to chemicals and other substances injurious to health from the environments, foods etc. These substances are taken into the body either consciously or unconsciously through the mouth, nose, and skin which often lead to oxidative stress, gene mutation, direct injury on cells and tissue, alteration of immune system etc, resulting in cancer development and other chronic and acute health challenges and death. This study is aimed at assessing the health risks due to chronic exposure to non-combusted Liquefied Petroleum Gas (LPG) and appraising the potential inflammatory and liver problem among its vendors who did not wear Personal Protective Equipments (PPE).

Methods: Forty-one apparently healthy Liquefied Petroleum Gas sellers and Forty-one apparently healthy non Liquefied Petroleum Gas sellers/user (control), aged 18 to 50 years were recruited for this study. The Body Mass Index (BMI) was determined by taking the ratio of weights in Kg to the square of heights in meters. Tumor Necrosis Factor Alpha (TNF-α) was estimated by Enzyme Linked Immunosorbent Assay (ELISA), 2-butanol was estimated using High Performance Liquid Chromatography (HPLC), ALT and AST were estimated using Colorimetric method. Data were analyzed using Student’s t-test and Pearson’s correlation at p<0.05.

Results: From the results obtained, AST, ALT and BMI did not show significant variation but TNF-α and 2-butanol showed a significant variation compared to control. TNF-α and 2-butanol showed a significant positive correlation among the exposed group. The duration of exposure does not appear to cause a significant difference in the levels of the biochemical parameters.

Conclusion: This study therefore showed that exposure to Liquefied Petroleum Gas has no effect on anthropometric and liver parameter but appears to cause significant elevation of TNF-α and 2-butanol, meaning that sellers may be predisposed to inflammation. It is therefore recommended that vendors of Liquefied Petroleum Gas (LPG) always wear their PPE to avoid deleterious effect on their health.
Analysis of Blood Culture Collection and Laboratory Processing Practices in Israel
Authors: Temkin Elizabeth , Biran Dikla , Braun Tali , Schwartz David , Carmeli Yehuda
Published: October 2022

Importance

Blood culturing is a critical diagnostic procedure affecting patient outcomes and antibiotic stewardship. Although there are standards for blood culturing, the process is not often measured.

Objectives

To evaluate processes related to the diagnosis of bloodstream infection and compare them with best practices.

Design, Setting, and Participants

A quality improvement study using laboratory data from January 1 to June 30, 2019, was conducted in 28 (96.6%) Israeli acute care hospitals. All blood cultures (BCs) performed on samples from adults and children in a period of 147 hospital-months were analyzed. Data analysis was performed from April 12, 2021, to September 9, 2022.

Main Outcomes and Measures

True pathogen detection rate, contamination rate, proportion of adults with blood cultures performed, proportion of adult culturing episodes with only 1 set or bottle used, and median time of steps from sample collection to pathogen identification.

Results

The data set consisted of 348 987 BC bottles. Bloodstream infection was detected in a median of 6.7% (IQR, 5.8%-8.2%) of adult culturing episodes and 1.1% (IQR, 0.7%-1.9%) of pediatric episodes. Eleven of 27 hospitals (40.7%) with adult patients met the standard of a contamination rate of less than 3% and only 2 hospitals (7.4%) met the more stringent standard of less than or equal to 1% contamination rate. The percentage of adults with blood cultures ranged from 2.7% to 29.0% (mean [SD], 15.7% [6.0%]). There was an association between sampling rate and pathogen detection until BCs were performed in 17% of adult admissions. The percentage of solitary BCs ranged from 47.8% to 94.4%. An estimated 1745 of 7436 (23.5%) adult bloodstream infections went undetected because solitary BCs were performed, anaerobic bottles were not used, or BCs were not performed. Median processing time was 51.2 (IQR, 33.9-78.0) hours, 3 times the optimal time: 4.4 (IQR, 1.7-12.5) hours for the preanalytical stage, 15.9 (IQR, 10.2-23.6) hours from incubation to growth detection, 4.5 (IQR, 1.5-10.7) hours from detection to Gram stain, and 30.9 (IQR, 22.0-41.9) hours from detection to isolate identification. An 8.6-hour delay was related to off-hours operating of laboratories.

Conclusions and Relevance

The findings of this study suggest that the multistep process of blood culturing is not managed comprehensively in Israel, leading to poor clinical practices and delayed results.
The applications of porous FO membranes and polyelectrolyte draw solution in the high‐salinity organic wastewater treatment with a hybrid forward osmosis‐membrane distillation system
Authors: Cao Zaizhi , Zhu Tengyi
Published: October 2022

Hybrid forward osmosis‐membrane distillation (FO‐MD) system have been considered as a promising technology for wastewater treatment. In the current study, initial and modified porous FO membranes are fabricated, and the intrinsic membrane separation properties are also investigated. Polyacrylic acid sodium (PAAS), sodium polystyrene sulfonate (PSS) and polyethylene glycol (PEG) are used to evaluate the effects of draw solution (DS) in FO experiments. Particularly, alkali treated modified porous FO membrane and PAAS are utilized in the subsequent wastewater treatment owing to the high performance of permeation and rejection. Furthermore, the optimal values of operating parameters (flow velocity, DS concentration and DS temperature), which are selected according to the effects of water flux (JV) in the FO and MD process, are evaluated and utilized to investigate the dynamic changes of JV in the high‐salinity organic wastewater treatment with hybrid FO‐MD system. Results show that the hybrid FO‐MD system with porous FO membranes and polyelectrolyte DS maintain the operation in a constant flux of 16.61 LMH, and the permeate solution can be effectively recovered with favorable quality. This study provides remarkable implications for the design of porous FO membranes and the application of hybrid FO‐MD system in the wastewater treatment.
Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout
Authors: Sumpter Nicholas A. , Takei Riku , Cadzow Murray , Topless Ruth K. G. , Phipps‐Green Amanda J. , Murphy Rinki , de Zoysa Janak , Watson Huti , Qasim Muhammad , Lupi Alexa S. , Abhishek Abhishek , Andrés Mariano , Crișan Tania O. , Doherty Michael , Jacobsson Lennart , Janssen Matthijs , Jansen Tim L. , Joosten Leo A. B. , Kapetanovic Meliha , Lioté Frédéric , Matsuo Hirotaka , McCarthy Geraldine M. , Perez‐Ruiz Fernando , Riches Philip , Richette Pascal , Roddy Edward , Stiburkova Blanka , So Alexander , Tausche Anne‐Kathrin , Torres Rosa J. , Uhlig Till , Major Tanya J. , Stamp Lisa K. , Dalbeth Nicola , Choi Hyon K. , Vazquez Ana I. , Leask Megan P. , Reynolds Richard J. , Merriman Tony R.
Published: October 2022

Objective

To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.

Methods

A 19‐variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex‐stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.

Results

The PRS was associated with earlier age at gout onset in men (β = –3.61 in years per unit PRS [95% confidence interval (95% CI) –4.32, –2.90] in European men; β = –6.35 [95% CI –8.91, –3.80] in East Polynesian men; β = –3.51 [95% CI –5.46, –1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI –2.32, 2.45] in European women; β = 0.20 [95% CI –7.21, 7.62] in East Polynesian women; β –3.33 [95% CI –9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = –2.42 [95% CI –3.37, –1.46] and β = –6.80 [95% CI –10.06, –3.55], respectively) but not in West Polynesian men (β = –1.79 [95% CI –4.74, 1.16]).

Conclusion

Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
Identification of Mechanisms by Which Genetic Susceptibility Loci Influence Systemic Sclerosis Risk Using Functional Genomics in Primary T Cells and Monocytes
Authors: González‐Serna David , Shi Chenfu , Kerick Martin , Hankinson Jenny , Ding James , McGovern Amanda , Tutino Mauro , Villanueva‐Martin Gonzalo , Ortego‐Centeno Norberto , Callejas José Luis , Martin Javier , Orozco Gisela
Published: October 2022

Objective

Systemic sclerosis (SSc) is a complex autoimmune disease with a strong genetic component. However, most of the genes associated with the disease are still unknown because associated variants affect mostly noncoding intergenic elements of the genome. We used functional genomics to translate the genetic findings into a better understanding of the disease.

Methods

Promoter capture Hi‐C and RNA‐sequencing experiments were performed in CD4+ T cells and CD14+ monocytes from 10 SSc patients and 5 healthy controls to link SSc‐associated variants with their target genes, followed by differential expression and differential interaction analyses between cell types.

Results

We linked SSc‐associated loci to 39 new potential target genes and confirmed 7 previously known SSc‐associated genes. We highlight novel causal genes, such as CXCR5, as the most probable candidate gene for the DDX6 locus. Some previously known SSc‐associated genes, such as IRF8, STAT4, and CD247, showed cell type–specific interactions. We also identified 15 potential drug targets already in use in other similar immune‐mediated diseases that could be repurposed for SSc treatment. Furthermore, we observed that interactions were directly correlated with the expression of important genes implicated in cell type–specific pathways and found evidence that chromatin conformation is associated with genotype.

Conclusion

Our study revealed potential causal genes for SSc‐associated loci, some of them acting in a cell type–specific manner, suggesting novel biologic mechanisms that might mediate SSc pathogenesis.
Describing settings of care in the last 100 days of life for cancer decedents: a population‐based descriptive study
Authors: Hafid Abe , Howard Michelle , Webber Colleen , Gayowsky Ana , Scott Mary , Jones Aaron , Hsu Amy T. , Tanuseputro Peter , Downar James , Conen Katrin , Manuel Doug , Isenberg Sarina R.
Published: October 2022

Background

Few studies have described the settings cancer decedents spend their end‐of‐life stage, with none considering homecare specifically. We describe the different settings of care experienced in the last 100 days of life by individuals with cancer and how settings of care change as they approached death.

Methods

A retrospective cohort study from January 2013 to December 2017, of decedents whose primary cause of death was cancer, using linked population‐level health administrative datasets in Ontario, Canada.

Results

Decedents 125,755 were included in our cohort. The average age at death was 73, 46% were female, and 14% resided in rural regions. And 24% died of lung cancer, 7% breast, 7% colorectal, 7% pancreatic, 5% prostate, and 50% other cancers. In the last 100 days of life, decedents spent 25.9 days in institutions, 25.8 days receiving care in the community, and 48.3 days at home without any care. Individuals who died of lung and pancreatic cancers spent the most days at home without any care (52.1 and 52.6 days), while individuals who died of prostate and breast cancer spent the least days at home without any care (41.6 and 45.1 days). Regardless of cancer type, decedents spent fewer days at home and more days in institutions as they approached death, despite established patient preferences for an end‐of‐life experience at home.

Conclusions

In the last 100 days of life, cancer decedents spent most of their time in either institutions or at home without any care. Improving homecare services during the end‐of‐life may provide people dying of cancer with a preferred dying experience.
Clustering on longitudinal quality‐of‐life measurements using growth mixture models for clinical prognosis: Implementation on CCTG/AGITG CO.20 trial
Authors: Zhang Jiahui , Kong Weili , Hu Pingzhao , Jonker Derek , Moore Malcolm , Ringash Jolie , Shapiro Jeremy , Zalcberg John , Simes John , Tu Dongsheng , O'Callaghan Chris J. , Liu Geoffrey , Xu Wei
Published: October 2022

Introduction

Analyzing longitudinal cancer quality‐of‐life (QoL) measurements and their impact on clinical outcomes may improve our understanding of patient trajectories during systemic therapy. We applied an unsupervised growth mixture modeling (GMM) approach to identify unobserved subpopulations (“patient clusters”) in the CO.20 clinical trial longitudinal QoL data. Classes were then evaluated for differences in clinico‐epidemiologic characteristics and overall survival (OS).

Methods and Materials

In CO.20, 750 chemotherapy‐refractory metastatic colorectal cancer (CRC) patients were randomized to receive Brivanib+Cetuximab (n = 376, experimental arm) versus Cetuximab+Placebo (n = 374, standard arm) for 16 weeks. EORTC‐QLQ‐C30 QoL summary scores were calculated for each patient at seven time points, and GMM was applied to identify patient clusters (termed “classes”). Log‐rank/Kaplan–Meier and multivariable Cox regression analyses were conducted to analyze the survival performance between classes. Cox analyses were used to explore the relationship between baseline QoL, individual slope, and the quadratic terms from the GMM output with OS.

Results

In univariable analysis, the linear mixed effect model (LMM) identified sex and ECOG Performance Status as strongly associated with the longitudinal QoL score (p < 0.01). The patients within each treatment arm were clustered into three distinct QoL‐based classes by GMM, respectively. The three classes identified in the experimental (log‐rank p‐value = 0.00058) and in the control arms (p < 0.0001) each showed significantly different survival performance. The GMM's baseline, slope, and quadratic terms were each significantly associated with OS (p < 0.001).

Conclusion

GMM can be used to analyze longitudinal QoL data in cancer studies, by identifying unobserved subpopulations (patient clusters). As demonstrated by CO.20 data, these classes can have important implications, including clinical prognostication.
Identification of a novel prognostic signature correlated with epithelial‐mesenchymal transition, N6‐methyladenosine modification, and immune infiltration in colorectal cancer
Authors: Qu Xiao , Tan Honghong , Mao Jingxian , Yang Mengxue , Xu Jian , Yan Xuebing , Wu Wenjuan
Published: October 2022

Objective

Colorectal cancer (CRC) is a commonly diagnosed human malignancy worldwide. Both epithelial‐mesenchymal transition (EMT) and N6‐methyladenosine (m6A) modification play a crucial role in CRC development. This study aimed to construct a prognostic signature based on the genes related to EMT and m6A modification.

Method

Firstly, the mRNA expression profiling of CRC tissues was analyzed using TCGA and GEO databases. The prognostic hub genes related to EMT and m6A modification were selected using weighted correlation network and cox regression analysis. The prognostic signature was constructed based on hub genes, followed by validation in three external cohorts. Finally, the expression of the representative hub gene was detected in clinical samples, and its biological role was investigated using assays in vivo and in vitro.

Results

A prognostic signature was constructed using the following genes: YAP1, FAM3C, NUBPL, GLO1, JARID2, NFKB1, CDKN1B, HOOK1, and GIPC2. The signature effectively stratified the clinical outcome of CRC patients in the training cohort and two validation cohorts. The subgroup analysis demonstrated the signature could identify high‐risk population from CRC patients within stage I‐II or III‐IV, female, male and elder patients. The signature was correlated with the infiltration of some immune cells (such as macrophage and regulatory T cells) and gene mutation counts. Finally, the hub gene GIPC2 was found to be downregulated in CRC tissues and most CRC cells lines. GIPC2 overexpression inhibited the malignant characteristics of CRC cells in vitro and in vivo through upregulating E‐cadherin and downregulating N‐cadherin, Vimentin, and Snail, while the opposite results were observed for GIPC2 knockdown in CRC cells.

Conclusion

Our present study for the first time constructed a novel prognostic signature related to EMT, m6A modification, and immune infiltration for CRC risk stratification. In addition, GIPC2 is identified as a promising clinical biomarker or therapeutical target for CRC.
The use of recombinant human platelet‐derived growth factor‐BB in combination with β‐tricalcium phosphate and rhPDGF‐BB in combination with freeze‐dried bone allograft plus barrier in two separate complex infrabony defects with long‐term follow‐up
Authors: McClain Pamela K.
Published: October 2022

Background

Reports from a large‐scale, prospective, masked, randomized controlled clinical trial demonstrated gain in attachment level, linear bone gain, and percentage bone fill in infrabony defects treated with recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) and β‐tricalcium phosphate (β‐TCP) at 6 months. A follow up to that trial at 24 months showed the results were stable in terms of gain in clinical parameters, and assessment of selective cases demonstrated stability at 5 years. The cases presented in this report provide clinical applications to support the use of this biologic in complex infrabony defects. An infrabony defect is described as a periodontal pocket with its base apical to the crest of the alveolar bone. Infrabony defects may have one, two, or three bony walls creating challenges in management.

Methods

Two complex infrabony defect cases are presented in this report: one using rhPDGF‐BB with β‐TCP and the other using rhPDGF‐BB with freeze‐dried bone allograft (FDBA) and a resorbable barrier membrane. The techniques are described with results showing long‐term follow up and reentry at 8 and 14 years (respectively).

Results

Both cases demonstrate significant gains in clinical attachment levels as well as bone‐like fill as observed radiographically and at reentry.

Conclusions

These case reports of combining rhPDGF‐BB with β‐TCP or with FDBA and a barrier membrane support the literature showing improvement in attachment levels and demonstrating bone fill in complex infrabony defects. The results can be maintained long term.
Vegetable Oil Hydrogenation over Pt Monolithic and Powder Catalysts: Experimental and Modeling Study
Authors: Troncoso Franco David , Pedrozo Hector Alejandro , Tonetto Gabriela Marta
Published: October 2022

A complete kinetic study was performed for the hydrogenation of vegetable oil using a powder and a monolithic Pt catalyst. The experimental studies were carried out at a wide interval of H2 pressure, temperature, and catalyst loading using Pt/γ‐Al2O3 powder catalyst in a slurry reactor and Pt/Al2O3/Al‐structured catalyst in a monolithic stirrer reactor. The mathematical model for the reactors includes the hydrogenation and isomerization reactions, the external gas‐liquid and liquid‐solid mass transfer as well as the internal mass transfer. Four kinetic models were evaluated for both catalysts. The best fit of the experimental data was obtained by adopting a Langmuir‐Hinshelwood kinetic model for the liquid reactant and a dissociative adsorption and zero‐order reaction for H2.
Breast cancer and cardiovascular outcomes after breast cancer in survivors of Hodgkin lymphoma
Authors: Krul Inge M. , Boekel Naomi B. , Kramer Iris , Janus Cécile P. M. , Krol Augustinus D. G. , Nijziel Marten R. , Zijlstra Josée M. , van der Maazen Richard W. M. , Roesink Judith M. , Jacobse Judy N. , Schaapveld Michael , Schmidt Marjanka K. , Opstal‐van Winden Annemieke W. J. , Sonke Gabe S. , Russell Nicola S. , Aleman Berthe M. P. , van Leeuwen Flora E.
Published: October 2022

Background

Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes.

Methods

The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC‐HL) with 5988 age‐ and calendar year‐matched patients with first primary BC (BC‐1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment.

Results

Compared to BC‐1 patients, BC‐HL patients received anthracycline‐containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast‐conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC‐HL patients. BC‐HL patients had a significantly higher risk of 15‐year overall mortality than BC‐1 patients (61% vs. 23%). Furthermore, risks of BC‐specific mortality and nonfatal BC events were significantly increased among BC‐HL patients, also when accounting for tumor and treatment characteristics (2.2‐ to 4.5‐fold). BC‐HL patients with a screen‐detected BC had a significantly reduced (61%) BC‐specific mortality. One‐third of BC‐HL patients had CVD at BC‐diagnosis, compared to <0.1% of BC‐1 patients. Fifteen‐year CVD‐specific mortality and CVD incidence were significantly higher in BC‐HL patients than in BC‐1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment.

Conclusions

BC‐HL patients experience a higher burden of CVD and worse BC outcomes than BC‐1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.

Lay summary

Patients with breast cancer after Hodgkin lymphoma (BC‐HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD).

BC treatment considerations were reported for 71% of BC‐HL patients.

We examined whether BC‐HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC‐1).

We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC‐1 patients.

Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.
Lignin‐derived carbon materials for catalysis and electrochemical energy storage
Authors: Wang Huan , Feng Pingxian , Fu Fangbao , Yu Xuefeng , Yang Dongjie , Zhang Wenli , Niu Li , Qiu Xueqing
Published: October 2022

Lignin is abundant in green biomass. However, most of the lignin remains to be utilized. Lignin‐derived carbons (LDCs) provide a feasible approach for lignin valorization. Owing to the coupling merits of low cost, tunable morphologies, and high porosity, LDC materials have drawn extensive attention in the fields of catalysis and electrochemical energy storage. This review summarizes the recent advances in LDC materials and their applications in catalysis, supercapacitors, and secondary batteries. The bottlenecks and future trends are proposed for the further development of advanced LDCs. This review is expected to guide the preparation of high‐value‐added LDCs.
Impact of improving severity of secondary mitral regurgitation on survival
Authors: Sannino Anna , Banwait Jasjit K. , Sudhakaran Sivakumar , Rahimighazikalayeh Gelareh , Szerlip Molly , Smith Robert , Esposito Giovanni , Mack Michael J. , Grayburn Paul A.
Published: October 2022

Aims

Secondary mitral regurgitation (SMR) is frequent in patients with heart failure with reduced ejection fraction (HFrEF) and portends detrimental prognosis. Despite interventions addressing the mitral valve (MV) have been proven effective to improve survival, an important knowledge gap exists regarding the role of medical therapy (MT) in this context. Thus, we aimed at investigating the role of MT optimization in patients with SMR and HFrEF.

Methods and results

A total of 435 patients with SMR and HFrEF were retrospectively evaluated. Of those, 158 with severe SMR were finally included, with 63 (40%) managed with MT alone and 96 (60%) with MV intervention plus MT. Echocardiography was performed after 30 days of MT optimization or MV intervention. Responders were patients with a final mitral regurgitation (MR) grade of ≤2+. Survival data were gathered through the National Database Index and patient chart review. MR severity improved in 131 patients (100% MV intervention; 57% MT) but stayed the same or worsened in 27 patients. Responders and non‐responders were similar for baseline characteristics. Overall, long‐term survival of responders was significantly higher than non‐responders [hazard ratio (HR) 0.55, 95% confidence interval (CI) (0.32–0.96), P = 0.032]. No difference in survival was observed when evaluated by intervention type in the overall population (MT alone, n = 63; MV intervention plus MT, n = 95) [HR 0.77, 95% CI (0.48–1.26), P = 0.3], nor within responder group (MT alone, n = 36; MV intervention plus MT, n = 95) [HR 1.03, 95% CI (0.56–1.89), P = 0.94].

Conclusions

MT reduces SMR severity in 57% of the patients with severe SMR. A final SMR grade of ≤2+ is linked to improved survival, independently of the type of treatment they receive.
Optimal cardiometabolic health and risk of heart failure in type 2 diabetes: an analysis from the Look AHEAD trial
Authors: Patel Kershaw V. , Khan Muhammad Shahzeb , Segar Matthew W. , Bahnson Judy L. , Garcia Katelyn R. , Clark Jeanne M. , Balasubramanyam Ashok , Bertoni Alain G. , Vaduganathan Muthiah , Farkouh Michael E. , Januzzi James L. , Verma Subodh , Espeland Mark , Pandey Ambarish
Published: October 2022

Aims

To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D).

Methods and results

Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident HF events occurred over 12.4 years of follow‐up. The CMH score included 2 points each for target levels of waist circumference, glomerular filtration rate, urine albumin‐to‐creatinine ratio, and 1 point each for blood pressure and glycated haemoglobin at target. High baseline CMH score (6–8) was significantly associated with lower overall HF risk (adjusted hazard ratio [HR], ref = low score (0–3): 0.31, 95% confidence interval [CI] 0.21–0.47) with similar associations observed for HFpEF and HFrEF. Improvement in CMH was significantly associated with lower risk of overall HF (adjusted HR per 1‐unit increase in score at 4 years: 0.80, 95% CI 0.70–0.91). In the ACCORD validation cohort, the baseline CMH score performed well for predicting HF risk with adequate discrimination (C‐index 0.70), calibration (chi‐square 5.53, p = 0.70), and risk stratification (adjusted HR [high (6–8) vs. low score (0–3)]: 0.35, 95% CI 0.26–0.46). In the Look AHEAD subgroup with available biomarker data, incorporating N‐terminal pro‐B‐type natriuretic peptide to the baseline CMH score improved model discrimination (C‐index 0.79) and risk stratification (adjusted HR [high (8–10) vs. low score (0–4)]: 0.18, 95% CI 0.09–0.35).

Conclusions

Achieving target levels of more CMH parameters at baseline and sustained improvements were associated with lower HF risk in T2D.
A novel battery cooling system using nanofluids on MATLAB Simulink
Authors: Wankhede Sagar , Kamble Laxman V.
Published: October 2022

The battery pack is one of the crucial components in the creation of an electric car. Thus, its optimal and efficient functioning is of prime importance. Several issues are generated due to battery heating which may be fatal and can cause severe issues. The battery cooling system is one of the most effective ways to keep the battery pack at the ideal temperature for lithium‐ion cells to function properly. This article mainly focuses on MATLAB Simulink simulation‐based novel battery cooling system design using Nanofluids. In this simulation study, the employed nanofluids are compared mostly to ethylene glycol. The simulation findings demonstrated that employing nanofluid as the coolant cools the battery pack more quickly than using ethylene glycol. It was found that ethylene glycol can cool the battery pack within 480 seconds while with the use of nanofluids the battery pack was cooled in just 150 seconds considering the temperature cooling from 40°C to 25°C. The effective and fast cooling of Nanofluids is due to the higher value of thermal conductivity of the fluid which plays a major role in heat transfer. Thus, fluid properties mainly thermal conductivity must be focused upon and % concentration of nanoparticles in the base fluid must be increased to get more effective cooling.
Faculty fathers: Understanding the experiences of faculty men with children during the COVID‐19 pandemic
Authors: Blakewood Pascale Amanda , Ehrlich Suzanne , Hicks‐Roof Kristen
Published: October 2022

To effectively cultivate systems of equity, it is important to not only understand the experiences of those who are most affected by inequity but also of those who are in positions of power and privilege. This study explores how faculty men with children navigated the pandemic experience. Two major thematic findings emerged including ‘Not (as) Interrupted’ and ‘“I” feel supported’. These findings suggest that academic fathers may be emerging from the pandemic positioned differently than academic mothers. This research has implications for higher education administrators and faculty in the shaping of practice and policies aimed at equitably supporting faculty post‐pandemic.
The impact of stress associated with caring for patients with COVID‐19 on career decisions, resilience, and perceived self‐efficacy in newly hired nurses in Jordan: A cross‐sectional study
Authors: Al Hadid Lourance A. E. , Al Barmawi Marwa A. , Alnjadat Rafi , Farajat Lo'ai Al
Published: October 2022

Background and Aims

The decision to stay in nursing has been challenged by the recent coronavirus disease 2019 (COVID‐19) pandemic. New nurses joined the workforce and provided care to patients with COVID‐19 although they received limited training, which could have influenced their intention to stay in nursing. We aimed in this study to examine the impact of caring for patients with COVID‐19 on career decisions, resilience, and perceived self‐efficacy among newly hired nurses in Jordan. It also tested the predictors of intentions to stay among new nurses.

Methods

This cross‐sectional quantitative study was conducted using an online electronic questionnaire form. The sample included newly hired nurses (n = 300) working in public hospitals and providing care to patients with COVID‐19 in different levels of acuity units. The perceived stress scale and Connor−Davidson resilience scale 25 were used to measure stress and resilience among nurses.

Results

The majority chose nursing as their career, but they were not satisfied with the current work conditions or autonomy in decision‐making. Many nurses reported having moderate to high work‐related stress and low to moderate resilience. Among all variables in this study, financial income predicted mild intention to stay in nursing.

Conclusions

Nurses expressed the presence of work‐related stress and low to moderate levels of resilience. As new nurses, exposure to these stress levels might lead to burnout. Nursing managers should take necessary measures to promote better work conditions and improve resilience to avoid nurses leaving the profession at times when there is a shortage.