bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain tissue cerebrospinal fluid fraction increases quadratically in normal aging
Authors: Zhou Liangdong , Li Yi , Sweeney Elizabeth M. , Wang Xiuyuan H. , Kuceyeski Amy , Chiang Gloria C. , Ivanidze Jana , Wang Yi , Gauthier Susan A. , de Leon Mony J. , Nguyen Thanh D.
Published: February 2023

Background and Purpose

Our objective was to apply multi-compartment T2 relaxometry in cognitively normal individuals aged 20-80 years to study the effect of aging on the parenchymal cerebrospinal fluid fraction (CSFF), a measure of the microscopic-scale CSF space.

Materials and Methods

A total of 66 volunteers (age range, 22-80 years) were enrolled. Voxel-wise maps of short-T2 myelin water fraction (MWF), intermediate-T2 intra/extra-cellular water fraction (IEWF), and long-T2 CSFF were obtained using fast acquisition with spiral trajectory and adiabatic T2prep (FAST-T2) sequence and three-pool non-linear least squares fitting.

Multiple linear regression analysis with correction for multiple comparisons was performed to study the association between age and regional MWF, IEWF, and CSFF measurements, adjusting for sex and region of interest (ROI) volume. The cerebral white matter (WM), cerebral cortex, and subcortical deep gray matter (GM) were considered as ROIs. In each model, a quadratic term for age was tested using an ANOVA test. A Spearman’s correlation between the normalized lateral ventricle volume, a measure of organ-level CSF space, and the regional CSFF, a measure of tissue-level CSF space, was computed.

Results

In the multiple regression analysis, we found a statistically significant quadratic relationship between age and regional CSFF for all three ROIs (all p-values < 0.001). A statistically significant quadratic relationship with age was also found for MWF in the deep GM (p = 0.004) and IEWF in the cortex (p = 0.012). There was a statistically significant linear relationship between age and regional IEWF in the cerebral WM (p = 0.006) and deep GM (p = 0.002). In the univariate correlation analysis, the normalized lateral ventricle volume was found to correlate moderately with the regional CSFF measurement in the cerebral WM (ρ = 0.43, p < 0.001), cortex (ρ = 0.43, p < 0.001), and deep GM (ρ = 0.49, p < 0.001).

Conclusion

Brain tissue water residing in different water compartments shows complex changing patterns with age. Parenchymal CSFF, a biomarker of microscopic-scale CSF-like water, shows a quadratic increase in both GM and WM, starting approximately at the age of 50.
Enhanced Branched-Chain Amino Acid Metabolism Improves Age-Related Reproduction inC. elegans
Authors: Lesnik Chen , Kaletsky Rachel , Ashraf Jasmine M. , Sohrabi Salman , Cota Vanessa , Sengupta Titas , Keyes William , Luo Shijing , Murphy Coleen T.
Published: February 2023

Reproductive aging is one of the earliest human aging phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline. However, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute toC. elegansoocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductivedaf-2mutants. Here we show that the mitochondrial proteomic profiles of young wild-type anddaf-2worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover,bcat-1knockdown decreases oocyte quality indaf-2worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Importantly, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both bybcat-1overexpression and by supplementing with Vitamin B1, a cofactor needed for BCAA metabolism.
Distribution of ubiquilin 2 and TDP-43 aggregates throughout the CNS inUBQLN2p.T487I-linked amyotrophic lateral sclerosis and frontotemporal dementia
Authors: Nementzik Laura R. , Thumbadoo Kyrah M. , Murray Helen C. , Gordon David , Yang Shu , Blair Ian P. , Turner Clinton , Faull Richard L. M. , Curtis Maurice A. , McLean Catriona , Nicholson Garth A. , Swanson Molly E. V. , Scotter Emma L.
Published: February 2023

Mutations in theUBQLN2gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The neuropathology of suchUBQLN2-linked cases of ALS/FTD is characterised by aggregates of the ubiquilin 2 protein in addition to aggregates of the transactive response DNA-binding protein of 43 kDa (TDP-43). ALS and FTD withoutUBQLN2mutations are also characterised by TDP-43 aggregates, that may or may not colocalise with wildtype ubiquilin 2. Despite this, the relative contributions of TDP-43 and ubiquilin 2 to disease pathogenesis remain largely under-characterised, as does their relative deposition as aggregates across the central nervous system (CNS). Here we conducted multiplex immunohistochemistry of threeUBQLN2p.T487I-linked ALS/FTD cases, three non-UBQLN2-linked (sporadic) ALS cases, and eight non-neurodegenerative disease controls, covering 40 CNS regions. We then quantified ubiquilin 2 aggregates, TDP-43 aggregates, and aggregates containing both proteins in regions of interest to determine howUBQLN2-linked and non-UBQLN2-linked proteinopathy differ. We find that ubiquilin 2 aggregates that are negative for TDP-43 are predominantly small and punctate, and are abundant in the hippocampal formation, spinal cord, all tested regions of neocortex, medulla, and substantia nigra inUBQLN2-linked ALS/FTD but not sporadic ALS. Curiously, the striatum harboured small punctate ubiquilin 2 aggregates in all cases examined, while large diffuse striatal ubiquilin 2 aggregates were specific toUBQLN2-linked ALS/FTD. Overall, ubiquilin 2 is mainly deposited in clinically unaffected regions throughout the CNS such that symptomology inUBQLN2-linked cases maps best to the aggregation of TDP-43.
Robotic friction stir welding – seam-tracking control, force control and process supervision
Authors: Karlsson Martin , Bagge Carlson Fredrik , Holmstrand Martin , Robertsson Anders , De Backer Jeroen , Quintino Luisa , Assuncao Eurico , Johansson Rolf
Published: February 2023

Purpose

This study aims to enable robotic friction stir welding (FSW) in practice. The use of robots has hitherto been limited, because of the large contact forces necessary for FSW. These forces are detrimental for the position accuracy of the robot. In this context, it is not sufficient to rely on the robot’s internal sensors for positioning. This paper describes and evaluates a new method for overcoming this issue.

Design/methodology/approach

A closed-loop robot control system for seam-tracking control and force control, running and recording data in real-time operation, was developed. The complete system was experimentally verified. External position measurements were obtained from a laser seam tracker and deviations from the seam were compensated for, using feedback of the measurements to a position controller.

Findings

The proposed system was shown to be working well in overcoming position error. The system is flexible and reconfigurable for batch and short production runs. The welds were free of defects and had beneficial mechanical properties.

Research limitations/implications

In the experiments, the laser seam tracker was used both for control feedback and for performance evaluation. For evaluation, it would be better to use yet another external sensor for position measurements, providing ground truth.

Practical implications

These results imply that robotic FSW is practically realizable, with the accuracy requirements fulfilled.

Originality/value

The method proposed in this research yields very accurate seam tracking as compared to previous research. This accuracy, in turn, is crucial for the quality of the resulting material.
Local and sustainable production as vectors of an agrarian branding strategy in Catalonia: case study of the Baixa Tordera
Authors: de San Eugenio Vela Jordi , Ginesta Portet Xavier , Compte-Pujol Marc , Frigola-Reig Joan , Fernández-Rovira Cristina
Published: February 2023

Purpose

This paper aims to analyse the implications in terms of economic promotion and local development that ensue from the implementation of a strategy of agrarian branding in five municipalities in the Baixa Tordera region (Catalonia, Spain).

Design/methodology/approach

The research follows a case study logic. First, five focus groups were designed and distributed by sectors of activity. Second, six in-depth interviews were scheduled with opinion leaders from the region. Finally, a survey open to all inhabitants was set up on the town councils’ websites.

Findings

The brand understood as a device removed from the connotations of indiscriminate marketing should guarantee the following elements in its deployment and implementation: knowledge, recognition, complicity, development and denomination of origin.

Practical implications

This research contributes to improve the management models of agrarian spaces, but it also helps expand the research background on studies on agrarian branding.

Originality/value

The place brand must become something close to a denomination of origin that, informally, invites us to define the future of this agrarian area. It therefore also affects the complexity of the planning and development of this area which, from now on, must necessarily be supramunicipal. In this way, the brand needs to offer a holistic vision of the region to all the agents that work in the strategic and urban planning of the five municipalities under study.
How flexible pay can help employees in 2023
Authors: Brown David
Published: February 2023

Purpose

The UK is experiencing an extraordinary cost-of-living crisis as inflation and prices continue to rise. Energy bills are soaring, and food prices are rising to record rates, with no expectation that prices will drop in 2023. The current economic side effect is the rise of buy now pay later and the increasing reliance on credit cards. The purpose of this study is to evaluate whether employers introducing more flexible payment policies can improve the financial well-being of their employees.

Design/methodology/approach

The article analyses statistics and reports from various sources which provide detail on the impact of the cost-of-living crisis and the financial stress it causes on employees. The article evaluates sources and studies which explore the limitations of monthly pay and viable alternatives including flexible pay.

Findings

The article provides findings on the rise of short-term credit and buy now pay later schemes due to the cost-of-living crisis and how this is impacting on the workplace. The article discovers the significant benefits in introducing free flexible pay to employers and workers, from breaking the feast and famine cycle of monthly pay to improving well-being, productivity and absenteeism.

Originality/value

This research will be valuable for HR professionals and employers who are currently dealing with the cost-of-living crisis and are looking for cost-effective ways of helping employees financially in 2023.
Additional predictions for forensic DNA phenotyping of externally visible characteristics using the ForenSeq and Imagen kits
Authors: Elkins Kelly M. , Garloff Alexis T. , Zeller Cynthia B.
Published: February 2023

Multiplex DNA typing methods using massively parallel sequencing can be used to predict externally visible characteristics (EVCs) in forensic DNA phenotyping through the analysis of single‐nucleotide polymorphisms. The focus of EVC determination has focused on hair color, eye color, and skin tone as well as visible biogeographical ancestry features. In this study, we researched off‐label applications beyond what is currently marketed by the manufacturer of the Verogen ForenSeq kit primer set B and Imagen primer set E SNP loci. We investigated additional EVC predictions by examining published genome wide sequencing studies and reported allele‐specific gene expression and predictive values. We have identified 15 SNPs included in the ForenSeq kit panel and Imagen kits that have additional EVC prediction capabilities beyond what is published in the Verogen manuals. The additional EVCs that can be predicted include hair graying, ephelides hyperpigmented spots, dermatoheliosis, facial pigmented spots, standing height, pattern balding, helix‐rolling ear morphology, hair shape, hair thickness, facial morphology, eyebrow thickness, sarcoidosis, obesity, vitiligo, and tanning propensity. The loci can be used to augment and refine phenotype predictions with software such as MetaHuman for missing persons, cold case, and historic case investigations.
Steering Straight: Adapting suicide risk safety planning as a prevention‐focused self‐management resource for the Australian farming community
Authors: Duke Sonya , Macdonald Joanna , Kennedy Alison J.
Published: February 2023

Objective

This paper draws on the principles of suicide risk safety planning to co‐design a farming community resource for preventing and managing risks to mental health.

Setting

This project was undertaken in the Great South Coast Region of Victoria, Australia.

Participants

A working group (n = 6–8) from the Victorian farming community contributed to the iterative co‐design and co‐production of Steering Straight: My plan to keep on track. Twenty‐four members of the farming community pilot tested Steering Straight.

Design

Co‐design to develop, pilot and refine the resource with working group and target farming community.

Results

Steering Straight was viewed positively by the farming community as a tool that prompts prioritising well‐being; encourages reflection, planning and concrete steps towards taking action; helps set and meet personal goals; is simple and practical; and identifies pathways to support. Most participants (94%) completed Steering Straight on their own, taking approximately 15–30 min to create their personalised plan. Questions most likely to be filled in related to recognising personal signs of deteriorating well‐being and listing and planning enjoyable activities. A majority of participants (67%) kept a hard copy of their Steering Straight plan on hand to refer back to, while 78% expressed a preference for a digital version.

Conclusion

The co‐design and co‐production process resulted in a tailored prevention‐focused resource that was accepted and valued by the farming community.
Safety and efficacy of induction immunochemotherapy with rituximab, methotrexate, ifosfamide, and vincristine (R‐MIV) in patients with primary CNS lymphoma including recent COVID‐19 pandemic experience
Authors: Ostrowska Beata , Domanska‐Czyz Katarzyna , Romejko‐Jarosinska Joanna , Osowiecki Michal , Targonski Lukasz , Poplawska Lidia , Konecki Robert , Kotarska Martyna , Szymanski Marcin , Borawska Anna , Swierkowska Monika , Dabrowska‐Iwanicka Anna , Druzd‐Sitek Agnieszka , Paszkiewicz‐Kozik Ewa , Mroz‐Zycinska Ewa , Tajer Joanna , Wojciechowska‐Lampka Elzbieta , Osiadacz Wlodzimierz , Rymkiewicz Grzegorz , Lapinska Grazyna , Wojewodzka‐Mirocha Marta , Michalski Wojciech , Walewski Jan
Published: February 2023

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real‐world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID‐19 pandemic. In particular, treatment with high‐dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R‐MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high‐dose methotrexate (3.5 g/m2) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3–4 haematological toxicity was low for R‐MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment‐related toxicity. Co‐existence of SARS‐CoV‐2 infection with cytomegalovirus reactivation and the varicella‐zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression‐free and overall survival were not reached (median follow‐up: 44 months). In conclusion, the R‐MIV regimen is feasible in routine practice, effective and safe, even during the COVID‐19 pandemic.
Optical‐physical and inkjet printing properties of created hybrid CaCO3 coated papers
Authors: Yilmaz Ufuk
Published: February 2023

The aim of this study is to examine the role of different formulations of calcium carbonates on the inkjet printing quality, with the use of cationic carboxymethyl cellulose (CMC)‐starch as a binder in the formation of the coating structure of paper to use for inkjet printing. For this, GCC (ground calcium carbonate), PCC (precipitated calcium carbonate) and ECC (eggshell calcium carbonate), which have been tried as new coating materials in recent years, are mixed in different proportions to form a different coated formulation and plastered on the newly produced paper surface. Then, optical and physical tests of the obtained samples are carried out. Then, printing properties of the papers on which drop‐on‐demand system inkjet printing is made are examined. According to the obtained data, it is determined that the optical properties of coated paper with GCC + PCC blends outperformed papers coated with other blends. According to the physical test results, GCC + PCC blended coated papers showed the best performance in breaking length and tear indices. ECC + PCC blended coated papers however showed the best performance in burst indices. It is determined that as the particle size of the calcium carbonates in the coating materials decreased, the burst indices value also decreased. This situation is the opposite for breaking length and tear indices values. When the inkjet printing features are examined, it is seen that the best results are obtained from GCC + ECC coated papers in general. The most optimal metamerism indices results, measured under three different light sources, are obtained on GCC + PCC coated papers.
Anti‐SARS‐CoV‐2 spike immunoglobulin G and immunoglobulin M titers decline as interval from the second inactivated vaccine dose to the onset of illness is prolonged in breakthrough infection patients
Authors: Xu Chuan‐cai , He Zhi‐song , Lei Wei , Zhu Jin‐zhou , Zhao Da‐guo , Kong Jin‐dan , Wei Yao , Xu Ying , Huang Jian‐An
Published: February 2023

Background

Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) breakthrough infections is limited.

Methods

Ninety‐eight patients with coronavirus disease 2019 (COVID‐19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days.

Results

The median lymphocyte count and the median anti‐SARS‐CoV‐2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60‐day interval group compared with the corresponding medians in the ≥60‐day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin‐6 (IL‐6) level in the <60‐day interval group was significantly lower than the median IL‐6 level in the ≥60‐day interval group (p < 0.001).

Conclusions

Our results highlight the different anti‐SARS‐CoV‐2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness.
Understanding conflict among experts working on controversial species: A case study on the Australian dingo
Authors: Donfrancesco Valerio , Allen Benjamin L. , Appleby Rob , Behrendorff Linda , Conroy Gabriel , Crowther Mathew S. , Dickman Christopher R. , Doherty Tim , Fancourt Bronwyn A. , Gordon Christopher E. , Jackson Stephen M. , Johnson Chris N. , Kennedy Malcolm S. , Koungoulos Loukas , Letnic Mike , Leung Luke K.‐P. , Mitchell Kieren J. , Nesbitt Bradley , Newsome Thomas , Pacioni Carlo , Phillip Justine , Purcell Brad V. , Ritchie Euan G. , Smith Bradley P. , Stephens Danielle , Tatler Jack , van Eeden Lily M. , Cairns Kylie M.
Published: February 2023

Expert elicitation can be valuable for informing decision‐makers on conservation and wildlife management issues. To date, studies eliciting expert opinions have primarily focused on identifying and building consensus on key issues. Nonetheless, there are drawbacks of a strict focus on consensus, and it is important to understand and emphasize dissent, too. This study adopts a dissensus‐based Delphi to understand conflict among dingo experts. Twenty‐eight experts participated in three rounds of investigation. We highlight disagreement on most of the issues explored. In particular, we find that disagreement is underpinned by what we call “conflict over values” and “conflict over evidence.” We also note the broader role played by distrust in influencing such conflicts. Understanding and recognizing the different elements shaping disagreement is critical for informing and improving decision‐making and can also enable critique of dominant paradigms in current practices. We encourage greater reflexivity and open deliberation on these aspects and hope our study will inform similar investigations in other contexts.
Pharmacogenetic actionability and medication prescribing in people with cystic fibrosis
Authors: Anderson Justin D. , Davis Brittney H. , Giang Gracie , Jones April , Lee Cameron R. , Parker Kennedy , Searcy Heather , Benner Kim , Limdi Nita A. , Guimbellot Jennifer S.
Published: February 2023

Although major advancements have been made in the therapeutics for people with cystic fibrosis (PwCF), many still require the use of multiple medications to manage acute exacerbations of disease and maintain health. Iterative trial and error processes of pharmacotherapeutic management can be optimized by assessing and incorporating pharmacogenetics. For 82 PwCF, we reviewed 2 years of medication use and response history and interrogated metabolizer status for common pharmacogenes, revealing 3336 medication exposure events (MEEs) to 286 unique medications. As expected, the more frequent MEEs were those commonly used to treat cystic fibrosis (CF), such as antibiotics and respiratory medications. Antibiotics also comprised 56.7% of the undesirable drug responses. The impact of gene variants on drug responses was assessed using Pharmacogenomics Knowledgebase (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Thirty‐three (11.5%) medications have strong evidence of genetic influence on response as evidenced by gene‐based dosing guidelines. 110 (38.5%) unique medications had at least one association with a very important pharmacogene, whereas 143 (50%) were associated with at least one clinical or variant annotation. Over 97% of participants had at least one actionable genotype. Eleven (13.4%) patients with an actionable genotype, taking the impacted medication, had an undesirable drug response described in the CPIC guidelines that could potentially have been mitigated with a priori knowledge of the genotype. PwCF take many medications for disease management, with frequent dose changes to elicit a desired clinical effect. As CF care evolves, implementing pharmacogenetics testing can improve efficiency and safety of prescribing practices using precision selection and dosing at medication initiation.
Prognostic value of the preoperative albumin‐bilirubin score among patients with stages I–III gastric cancer undergoing radical resection: A retrospective study
Authors: Wang Xiang , Zheng Jingwei , Yang Hui , Yang Xinxin , Cai Wentao , Chen Xiaodong , Zhang Weiteng , Shen Xian
Published: February 2023

The albumin‐bilirubin (ALBI) score was originally used to accurately assess liver dysfunction and predict the prognoses of patients with hepatocellular carcinoma. Following its more recent application to patients with gastrointestinal tumors, this study analyzed the prognostic value of the ALBI score in Chinese patients with advanced resectable (tumor‐node‐metastasis [TNM] stages I–III) gastric cancer (GC). This study investigated 1185 patients with advanced GC, including 429 with TNM stage I. The patients were divided into training and verifications groups (593 and 592 patients, respectively) in which these patients were classified as high risk (ALBI score ≥ −2.65) or low risk (ALBI score < −2.65). Univariate and multivariate Cox regression analyses were performed, and a visual survival prediction model (nomogram) was created. On Kaplan–Meier analysis, patients who were low‐risk and high‐risk according to their ALBI scores had significantly different survival rates in both the training and verification groups (p < 0.01). The difference was also significant when analyzing only patients with TNM stage I GC (p = 0.031). Univariate and multivariate analyses showed that the ALBI score (p = 0.014), age (p < 0.001), Nutritional Risk Screening 2002 score (p = 0.024), sarcopenia (p = 0.049), tumor differentiation (p = 0.027), and TNM stage (p < 0.001) were independent risk factors for survival. Our survival prediction model that incorporated the ALBI score accurately predicted the 5‐year survival rate of Chinese patients with GC. Therefore, the ALBI score is a valid clinical indicator and good predictor of survival after surgery for progressive GC. Moreover, this score is simple to derive and does not burden patients with additional costs.
Examining network entry decisions in healthcare: Network and organizational characteristics
Authors: Yan Zhenzhen , Li Mei , Ni John Z. , McFadden Kathleen L.
Published: February 2023

Accountable Care Organizations (ACOs) are healthcare collaboration networks comprised of hospitals and other healthcare providers. The motivation behind the formation of ACOs is to improve the quality of care while reducing healthcare costs. Despite these commendable goals, hospitals’ participation in ACOs remains low; the most significant barrier being the risk associated with joining. Our research tackles this timely and potentially impactful topic by exploring factors that facilitate hospitals' ACO entry decisions. We apply resource dependence theory to explain that competition network characteristics, organizational network characteristics, and internal organizational characteristics mitigate hospitals’ financial risk and are therefore critical to ACO participation. Using survival analysis, we test our research hypotheses using longitudinal data from 3114 hospitals. Our findings suggest that hospitals with a high level of competition network centrality are more likely to join an ACO, while hospitals with a high level of competition network tie diversity are less likely to join. In addition, hospitals with experience in joining other healthcare networks, such as Regional Healthcare Information Organizations, or belonging to a large parent group, are inclined to enter an ACO. Lastly, hospitals with a high level of unabsorbed slack are prone to ACO participation. Given that knowledge of hospitals’ participation in ACOs is lacking, this research is relevant for practitioners in the US healthcare industry. Specifically, it provides insights for hospital administrators on the critical resources that need to be strengthened before joining an ACO. Our findings also provide practical guidance for healthcare policy makers on how to profile, target, and efficiently promote ACO participation among hospitals.
Does immune dysregulation contribute towards development of hypopigmentation in Indian post kala‐azar dermal leishmaniasis?
Authors: Sengupta Ritika , Mitra Sneha , Dighal Aishwarya , Moulik Srija , Chaudhuri Surya Jyati , Das Nilay Kanti , Chatterjee Uttara , Chatterjee Mitali
Published: February 2023

Post kala‐azar dermal leishmaniasis (PKDL), a sequel of apparently cured visceral leishmaniasis (VL) presents with papulonodular (polymorphic) or hypopigmented lesions (macular) and is the proposed disease reservoir. As hypopigmentation appears consistently in PKDL, especially the macular form, this study aimed to delineate immune factors that singly or in combination could contribute towards this hypopigmentation. At lesional sites, the presence of melanocytes and CD8+ T‐cells was assessed by immunohistochemistry and mRNA expression of melanogenic markers (tyrosinase, tyrosinase‐related protein‐1 and MITF) by droplet digital PCR, while plasma levels of cytokines and chemokines were measured by a multiplex assay. In comparison with skin from healthy individuals, macular PKDL demonstrated a near total absence of Melan‐A+ cells at dermal sites, while the polymorphic cases demonstrated a 3.2‐fold decrease, along with a dramatic reduction in the expression of key enzymes related to the melanogenesis signalling pathway in both forms. The levels of circulating IFN‐γ, IL‐6, IL‐2, IL‐1β, TNF‐α and IFN‐γ‐inducible chemokines (CXCL9/10/11) were elevated and was accompanied by an increased lesional infiltration of CD8+ T‐cells. The proportion of CD8+ T‐cells correlated strongly with plasma levels of IFN‐γ (r = 0.8), IL‐6 (r = 0.9, p < 0.05), IL‐2 (r = 0.7), TNF‐α (r = 0.9, p < 0.05) and IL‐1β (r = 0.7), as also with CXCL9 (r = 0.5) and CXCL10 (r = 0.6). Taken together, the absence/reduction in Melan‐A suggested hypopigmentation in PKDL was associated with the destruction of melanocytes, following the impairment of the melanogenesis pathway. Furthermore, the presence of CD8+ T‐cells and an enhanced IFN‐γ‐associated immune milieu suggested the generation of a pro‐inflammatory landscape that facilitated melanocyte dysfunction/destruction.
Coherence among Oregon Coast coho salmon populations highlights increasing relative importance of marine conditions for productivity
Authors: Davis Melanie J. , Anthony James , Ward Eric J. , Firman Julie , Lorion Christopher
Published: February 2023

Anadromous fishes, such as Pacific salmon, spend portions of their life cycle in freshwater and marine systems, thus rendering them susceptible to a variety of natural and anthropogenic stressors. These stressors operate at different spatiotemporal scales, whereby freshwater conditions are more likely to impact single populations or subpopulations, while marine conditions are more likely to act on entire evolutionarily significant units (ESUs). Coherence in population parameters like survival and productivity can therefore serve as an indicator of relative influence. The goal of this study was to elucidate scale‐dependent shifts in Oregon Coast coho salmon productivity. We used a multivariate state‐space approach to analyze almost 60 years of stock‐recruitment data for the Oregon Coast ESU. Analyses were conducted separately for time periods prior to and after 1990 to account for improvements in abundance estimation methods and significant changes in conservation and management strategies. Prior to 1990, productivity declined for most Oregon Coast populations, especially through the 1980s. From 1990–onward, coherence increased, and trends tracked closely with the North Pacific Gyre Oscillation (NPGO). The latter period is associated with reductions in harvest rates and hatchery production such that the relative influence of the marine environment may have grown more apparent following the removal of these stressors. Furthermore, the link between productivity and NPGO is consistent with trends observed for several other Pacific salmon ESUs. If Oregon Coast coho salmon populations become more synchronous, managers can expect to face new challenges driven by reductions in the population portfolio effect and increasingly variable marine conditions due to climate change.
Effects of thyme on halitosis in gingivitis patients: Can thyme mouthwash prevent halitosis—A randomized trial
Authors: Altındal Dicle , Deveci Kübra Ceran , Öner Talmaç Ayşe Gül , Talmaç Ahmet Cemil , Çalışır Metin
Published: February 2023

Objectives

Bad breath is a condition that negatively affects people's social interactions and quality of life. The aim of this study was to evaluate the effect of thyme mouthwash on intraoral halitosis, gingival index (GI) and plaque index (PI) in patients with gingivitis.

Methods

In this retrospective study, 60 gingivitis patients (30 women/30 men) received initial periodontal treatment followed by oral hygiene instructions (OHI) and then were divided into four groups: The control group (C) received only OHI, while chlorhexidine (CHX) mouthwash was prescribed to the CHX group, Zinc acetate and CHX diacetate mouthwash was prescribed to the zinc acetate and CHX diacetate (ZnA) group, and the thyme (T) group was instructed to use thyme mouthwash. GI, PI and volatile sulfur compound (VSC) values were recorded at baseline and at the first week of treatment.

Results

The initial values of the recorded parameters did not differ significantly between the groups. In all groups, VSCs, GI and PI decreased after treatment (p = 0.001). There was no significant difference between the PI values of the groups after treatment (p = 0.188). On the contrary, the GI and VSC values after treatment were significantly different between the groups (p = 0.001). GI values were highest in the control group and lowest in the CHX group. In terms of VSCs, a significant difference was found between groups T and C, and between groups T and ZnA (p = 0.001).

Conclusion

This study showed that the use of thyme mouthwash after periodontal treatment was effective in improving bad breath and gingivitis in gingivitis patients.
Identifying patterns of lifestyle behaviours linked to sociodemographic characteristics and health conditions among young adults in South Korea
Authors: Choi JiSun , Yun Eun Kyoung , Byun Hye Min
Published: February 2023

Aims

To identify specific patterns of lifestyle behaviours among young adults and examine the relationships of the patterns to sociodemographic characteristics and health conditions (hypertension, diabetes and obesity).

Design

Descriptive, correlational study.

Methods

Data from a nationally representative sample of 4562 young adults aged 19–39, who participated in the 2016–2018 Korea National Health and Nutrition Examination Survey, were analysed. Latent class analysis was used to identify the patterns of lifestyle behaviours, including smoking, alcohol use, physical activity and vaccination. Generalized linear regression analysis was used to examine the relationships among lifestyle behaviour patterns, sociodemographic characteristics and health conditions.

Results

Three patterns of lifestyle behaviours were identified: physically active (6.9%), high risk (21.5%) and passive (71.6%). The membership of these three patterns was significantly associated with sociodemographic characteristics (age, sex, education level, occupation and living arrangement). Among the three groups, young adults in the high‐risk group were found to be significantly associated with all three health conditions (hypertension, diabetes and obesity) while controlling for sociodemographic characteristics.

Conclusion

These results indicate that young adults are likely to engage in unhealthy lifestyle behaviours that are related to individual socioeconomic conditions, which could negatively affect their health conditions.

Impact

This study provides insights into the lifestyle behaviours among young adults who have been recognized to be socially disadvantaged. This could help develop education and prevention programmes tailored to specific patterns of lifestyle behaviours for improving health while considering their socioeconomic contexts.

No Patient or Public Contribution

This applies to this research as the focus was on young adults in South Korea only.
A new method to explicitly estimate the shift of optimum along gradients in multispecies studies
Authors: Mourguiart Bastien , Liquet Benoit , Mengersen Kerrie , Couturier Thibaut , Mansons Jérôme , Braud Yoan , Besnard Aurélien
Published: February 2023

Aim

Optimum shifts in species–environment relationships are intensively studied in a wide range of ecological topics, including climate change and species invasion. Numerous statistical methods are used to study optimum shifts, but, to our knowledge, none explicitly estimate it. We extended an existing model to explicitly estimate optimum shifts for multiple species having symmetrical response curves. We called this new Bayesian hierarchical model the Explicit Hierarchical Model of Optimum Shifts (EHMOS).

Location

All locations.

Taxon

All taxa.

Methods

In a simulation study, we compared the accuracy of EHMOS to a mean comparison method and a Bayesian generalized linear mixed model (GLMM). Specifically, we tested if the accuracy of the methods was sensitive to (1) sampling design, (2) species optimum position and (3) species ecological specialization. In addition, we compared the three methods using a real dataset of investigated optimum shifts in 24 Orthopteran species between two time periods along an elevation gradient.

Results

Of all the simulated scenarios, EHMOS was the most accurate method. GLMM was the most sensitive method to species optimum position, providing unreliable estimates in the presence of marginal species, that is, species with an optimum close to a sampling boundary. The mean comparison method was also sensitive to species optimum position and ecological specialization, especially in an unbalanced sampling design, with high negative bias and low interval coverage compared to EHMOS. The case study results obtained with EHMOS were consistent with what is expected considering ongoing climate change, with mostly upward shifts, which further improved confidence in the accuracy of the EHMOS method.

Main Conclusions

Explicit Hierarchical Model of Optimum Shifts could be used for a wide range of topics and extended to produce new insights, especially in climate change studies. Explicit estimation of optimum shifts notably allows investigation of ecological assumptions that could explain interspecific variability of these shifts.
The role of poly (ADP‐ribose) glycohydrolase in phosphatase and tensin homolog deficiency endometrial cancer
Authors: Sun Yanyan , Shi Yi , Liu Hui , Lv Chunmei , Zhang Aihua
Published: February 2023

Aim

To explore the relationship between poly(ADP‐ribose) glycohydrolase (PARG) and the occurrence, development, and prognosis of endometrial carcinoma (EC), and investigate whether the PARG inhibitor PDD0017273 could increase the sensitivity of EC cells to cisplatin.

Methods

The expression of PARG, phosphatase and tensin homolog (PTEN), and p53 in normal endometrial tissues (NE), endometrial hyperplasia without atypia (EH), atypical endometrial hyperplasia (AH), and EC was detected by immunohistochemistry. AN3CA EC cells with PTEN deficiency were treated with different cisplatin and PDD0017273, alone or in combination. Cell proliferation was detected by MTT method, apoptosis was detected by flow cytometry, and the expression of PARG in EC cells after treatment with different drugs was detected by western blot and immunohistochemistry.

Results

Expression of PARG in NE, EH, AH, and EC increased gradually. In addition, compared with low PARG expression in PTEN‐positive EC, patients who had high PARG expression in PTEN‐negative EC had more advanced clinical stages (r = −0.399, p = 0.032) and shorter overall survival time (p = 0.037). A dose of 40 μM PDD0017273 effectively inhibited PARG expression, increased the sensitivity of AN3CA cells to cisplatin.

Conclusions

The findings suggest that PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of EC. Moreover, PARG inhibition produced antitumor effects and increased the sensitivity of EC cells with PTEN deficiency to cisplatin.
Antenatal corticosteroids‐to‐delivery interval associates cord blood S100B levels
Authors: Fuma Kazuya , Kotani Tomomi , Ushida Takafumi , Imai Kenji , Iitani Yukako , Nakamura Noriyuki , Miki Rika , Katsuki Satoru , Kinoshita Fumie , Sato Yoshiaki , Hayakawa Masahiro , Kajiyama Hiroaki
Published: February 2023

Aim

Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS‐to‐delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS‐to‐delivery interval on cord blood S100 calcium‐binding protein B (S100B) levels as a biomarker of brain damage.

Methods

Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS‐to‐delivery interval, retrospectively: non‐ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels.

Results

Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non‐ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001).

Conclusions

Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.
The interaction between the histone acetyltransferase complex Hat1‐Hat2 and transcription factor AmyR provides a molecular brake to regulate amylase gene expression
Authors: Hu Yueyan , Liu Zhongjiao , Xu Shaohua , Zhao Qinqin , Liu Guodong , Song Xin , Qu Yinbo , Qin Yuqi
Published: February 2023

The chromatin structure is generally regulated by chromatin remodelers and histone modifiers, which affect DNA replication, repair, and levels of transcription. The first identified histone acetyltransferase was Hat1/KAT1, which belongs to lysine (K) acetyltransferases. The catalytic subunit Hat1 and the regulatory subunit Hat2 make up the core HAT1 complex. In this study, the results of tandem affinity purification and mass spectrometry and bimolecular fluorescence complementation proved that the Penicillium oxalicum PoHat1‐Hat2 is the transcriptional cofactor of the sequence‐specific transcription factor PoAmyR, a transcription activator essential for the transcription of amylase gene. ChIP‐qPCR results demonstrated that the complex PoHat1‐Hat2 is recruited by PoAmyR to the promoters of prominent amylase genes Poamy13A and Poamy15A and performs histone H4 lysine12 acetylation. The result of the yeast two‐hybrid test indicated that PoHat2 is the subunit that directly interacts with PoAmyR. PoHat1‐Hat2 acts as the molecular brake of the PoAmyR‐regulating transcription of amylase genes. A putative model for amylase gene regulation by PoAmyR‐Hat2‐Hat1 was constructed. Our paper is the first report that the Hat1‐Hat2 complex acts as a cofactor for sequence‐specific TF to regulate gene expression and explains the mechanism of TF AmyR regulating amylase genes expression.
Generation Z goes to math class: How the effective mathematics teaching practices can support a new generation of learners
Authors: Marin Katherine Ariemma , White Stephanie J.
Published: February 2023

Middle and high school students are part of Generation Z (birth years 1997–2012), a group that is emerging as very different from their parents and teachers. This article considers ways that generational research about Generation Z learners and NCTM's Effective Mathematics Teaching Practices can be used to inform and innovate practice in the mathematics classroom. Research suggests that while Generation Z learners are digitally engaged, they often display a lack of tech savvy. Generation Z students thrive on personalization and are often uncomfortable with collaborative learning. And the social movements of the early 2000s have shaped their world view. The authors provide resources, such as real‐world tasks rooted in social problems, and instructional suggestions for teachers. Teachers who consider the characteristics and preferences of Generation Z in their planning can enact mathematics lessons that better connect to Generation Z learners. With the Effective Mathematics Teaching Practices as a guide, teachers can design and deliver innovative lessons that support Generation Z learners to promote deeper understanding of mathematical content.
Forum theatre for training residents to be allies
Authors: O'Connor Alec B. , Gorgone Matthew , Rizk Nina , Gaughf Carli , Gracey Catherine F. , Shaw Margie Hodges , Morgan Adrienne
Published: February 2023

Background

Residents are commonly targets and bystanders of workplace discrimination, yet little is known about how best to train residents to manage these incidents. We sought to train residents to respond effectively to being a target or bystander of discrimination.

Approach

We used a novel, 75‐min theatrical role‐playing intervention called Theatre for Healthcare Equity (T.H.E.) to teach 71 internal medicine residents between December 2017 and February 2018. In T.H.E. residents took turns acting as either a ‘resident’ target or a ‘student’ bystander in a simulated scenario of discrimination. A facilitator led follow‐up discussions including group reflection and development of learning scripts to help with difficult situations. A post‐graduation survey was sent in November 2021 to assess residents' retention of knowledge, attitudes and potential application in practice.

Evaluation

T.H.E. was well received by residents, though survey response rates were low. All respondents to a post‐session survey reported having acquired knowledge and skills to help them respond to incidents of bias and discrimination. Most respondents to the post‐graduation survey nearly 4 years later remembered T.H.E.; seven wrote reflective narrative responses indicating that T.H.E. had raised awareness of these issues, empowered them to speak up on behalf of colleagues and validated their emotional reactions to hurtful speech from patients. We describe an incident in which a former resident attributed his ability to serve as an effective bystander ally to participating in T.H.E. years earlier.

Implications

T.H.E. was an efficient, well‐received intervention that some of our residents found to have been helpful years later. We continue to use T.H.E. as the basis for periodic ongoing allyship training for residents and teaching faculty to improve the inclusiveness of our clinical learning environment.
Pitfalls of using sequence databases for heterologous expression studies – a technical review
Authors: Maxeiner Stephan , Krasteva‐Christ Gabriela , Althaus Mike
Published: February 2023

Synthesis of DNA fragments based on gene sequences that are available in public resources has become an efficient and affordable method that has gradually replaced traditional cloning efforts such as PCR cloning from cDNA. However, database entries based on genome sequencing results are prone to errors which can lead to false sequence information and, ultimately, errors in functional characterisation of proteins such as ion channels and transporters in heterologous expression systems. We have identified five common problems that repeatedly appear in public resources: (1) Not every gene has yet been annotated; (2) not all gene annotations are necessarily correct; (3) transcripts may contain automated corrections; (4) there are mismatches between gene, mRNA and protein sequences; and (5) splicing patterns often lack experimental validation. This technical review highlights and provides a strategy to bypass these issues in order to avoid critical mistakes that could impact future studies of any gene/protein of interest in heterologous expression systems.

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