bluuebunny/crossref_metadata_2025 huggingface dataset:
Does cooperation with multiple actors diffuse the government’s responsibility in the implementation of COVID-19 measures?
Authors: Iseki Tatsuya , Shigemura Sohei , Ikeda Shun , Ishima Hideo
Published: January 2024

To manage the COVID-19 pandemic, the Japanese government has cooperated with multiple actors, such as experts, prefectural governments, and medical professionals, who generally attract limited attention in non-crisis times. While cooperation with such actors allows the central government to mobilize knowledge and utilize resources it does not have, such collaboration could diffuse the responsibility of COVID-19-related measures onto other actors. To empirically test this conjecture, we conducted an online survey experiment prior to the 2021 Japanese general election. It investigated whether the government’s cooperation with experts, prefectural governors, medical professionals, and the International Olympic Committee obscured its responsibility in the declaration of stay-at-home advisories, securing of beds, and conducting of the 2020 Summer Olympic Games. The results deliver no evidence that informing people of the influence of any actor diffused the government’s responsibility for the implementation of COVID-19-related measures. The findings of this study imply that the Japanese people held the national government accountable even during the COVID-19 pandemic.
Job Loss and Household Labor Supply Adjustments in Developing Countries: Evidence from Argentina
Authors: Ciaschi Matías , Neidhöfer Guido
Published: January 2024

Using longitudinal data for Argentina, this paper estimates the labor supply reaction of spouses and children, as well as the interactions between them, following the job loss of their husband or father. The findings show that job loss by the household head has a positive and significant impact on the labor supply of other household members. However, it increases the likelihood of spouses to switch to informal and downgraded employment, and of children to drop out from education. While effects are stronger among vulnerable households, coverage of social security does not provide enough support in coping with unemployment shocks. Mothers’ labor participation, however, may allow their daughters to continue their education.
Group III secreted phospholipase A2‐driven lysophospholipid pathway protects against allergic asthma
Authors: Hamu‐Tanoue Asako , Takagi Koichi , Taketomi Yoshitaka , Miki Yoshimi , Nishito Yasumasa , Kano Kuniyuki , Aoki Junken , Matsuyama Takahiro , Kondo Kiyotaka , Dotake Yoichi , Matsuyama Hiromi , Machida Kentaro , Murakami Makoto , Inoue Hiromasa
Published: January 2024

Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A2s (PLA2s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro‐asthmatic lipid mediators, but an understanding of the association between individual PLA2 subtypes and asthma is still incomplete. Here, we show that group III‐secreted PLA2 (sPLA2‐III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA2‐III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)‐induced asthma model, Pla2g3−/− mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA‐specific IgE production, and type 2 cytokine expression as compared to Pla2g3+/+ mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA‐challenged Pla2g3−/− mice relative to Pla2g3+/+ mice. LPA receptor 2 (LPA2) agonists suppressed thymic stromal lymphopoietin (TSLP) expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in Pla2g3−/− mice, suggesting that sPLA2‐III negatively regulates allergen‐induced asthma at least by producing LPA. Thus, the activation of the sPLA2‐III‐LPA pathway may be a new therapeutic target for allergic asthma.
Crocus sativus L. produces anti-inflammatory effects and regulates the NLRP3–NF-κB pathway
Authors: Yang Liang , Xu Huanhua , Hong Qian , Xu Nuo , Zhang Yan , Tao Rui , Li Shuai , Zhang Zizheng , Geng Jiahao , Wang Zihan , Hu Huizi , Dong Yan , Chu Zhaoyi , Zheng Bin , Zhu Jinmiao , Geng Ming , Gao Yue
Published: January 2024

Objective:

This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus (Crocus sativus) and explore the underlying mechanism.

Methods:

Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C. sativus. A xylene-induced inflammation model or lipopolysaccharide (LPS)-induced inflammation model was used in this study. C. sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in mouse serum. Hematoxylin and eosin (H&E) staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) protein levels within the nuclear factor-kappa B (NF-κB) pathway were assessed using western blotting. RAW264.7 cells were treated with LPS (5 μg/mL) and LPS + C. sativus (0.05, 0.1, and 0.2 mg/mL) for 24 h, and a Cell Counting Kit-8 was used to measure cell proliferation. Changes in NLRP3 and NF-κB levels were evaluated by western blotting.

Results:

Petal and stamen extracts of C. sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model. These extracts also decreased the concentrations of TNF-α and IL-1β in the mouse serum in the LPS-induced inflammation model. C. sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro. Carbonyl Cyanide3-ChloroPhenylhydrazone (CCCP) weakened the effects of C. sativus on the NLRP3–NF-κB pathway.

Conclusion:

C. sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.
Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas
Authors: Goto So , Maeda Naoyuki , Ohnuma Kazuhiko , Lawu Tjundewo , Ogawa Keiko , Sugiyama Saori , Matsumaru Maki , Noda Toru
Published: January 2024

Purpose:

To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas.

Setting:

National Hospital Organization, Tokyo Medical Center, Japan.

Design:

Retrospective case series.

Methods:

Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance.

Results:

The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01).

Conclusions:

The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.
Safety Climate in the Utility Industry
Authors: Huang Yueng-hsiang , Lee Jin , Perry MacKenna , He Yimin , Tondokoro Tsukumi
Published: January 2024

Objectives

This study aims to extend safety climate research by considering perceptions across the following three hierarchical levels within a workplace: (1) senior leaders/executives, (2) field leaders/supervisors, and (3) front-line employees.

Methods

We conducted a quantitative survey study at a US utility company where we collected data related to safety climate perceptions and employee-reported safety behaviors across the different levels of organizational hierarchy.

Results

The findings revealed the highest safety climate scores among senior leaders/executives, followed by field leaders/supervisors, and then employees, suggesting potential discrepancies between espoused and enacted safety values in the workplace.

Conclusions

These results suggest that supervisors and top managers may have different mental models of workplace safety compared with employees. Consequently, assessing perceptions at different organizational levels provides a fuller picture of safety in the workplace.
Greater Emotional and Psychological Well-being Are Associated With Reduced Employee Self-report Illness-Related Absenteeism
Authors: Fannin Austin , Hooley Cole , Nelson Erik J.
Published: January 2024

Objective

The purpose of this study is to determine the relationship that emotional, psychological, and social well-being has with self-reported illness-related absenteeism.

Methods

This study examines the relationship between three dimensions of well-being (emotional, psychological, and social) and self-report illness-related absenteeism among 133 workers spanning multiple industries across 16 different companies. This secondary, cross-sectional data were analyzed using multiple linear regression.

Results

As hypothesized, emotional well-being and psychological well-being were found to be negatively associated with absenteeism, with emotional well-being being the stronger predictor. Contrary to our hypothesis, we found that social well-being was not associated with absenteeism among workers.

Conclusions

Employee emotional well-being and psychological well-being are associated with self-reported illness-related absenteeism. Future work should explore causal relationships between these constructs.
Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis
Authors: Leonhardt Carl-Stephan , Hank Thomas , Pils Dietmar , Gustorff Charlotte , Sahora Klaus , Schindl Martin , Verbeke Caroline S. , Strobel Oliver , Klaiber Ulla
Published: January 2024

Background:

A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial.

Methods:

Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively.

Results:

Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57–1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39–1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39–1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30–2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies.

Conclusion:

After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
An exploration of how practitioners make meaning in a Chinese medicine consultation and treatment
Authors: Moir Felicity Clare
Published: January 2024

In Chinese medicine, practitioners assess patients’ complaints, analyze their underlying problems, identify causes and come to a diagnosis, which then directs treatment. What is not obvious and not recorded in a consultation is the clinical reasoning process that practitioners use. The research filmed three practitioners in the UK while they conducted a consultation and treatment on new patients. The practitioners and researchers viewed the films and used them as aide-memoirs, the reasoning process throughout was discussed. In order to determine the pattern, practitioners used the four examinations to gather information from the patient in an iterative process; their aesthetic reasoning was highly developed. Through triangulation they checked the information they received against a detailed understanding of the qi-dynamic. They used highly analytical strategies of forward (inductive) and backward (deductive) reasoning against the prototypes of the signs and symptoms that indicate a specific Zheng. This was achieved through an abductive process that linked description with explanation and causal factors with pathological mechanisms. The feedback loop with the patient continued through the consultation and into the treatment. A process of translation and interpretation was needed to turn the patient’s story into the practitioner’s story of qi-dynamics that then directed the treatment.Awareness of our clinical reasoning process will mitigate against biases, improve our diagnoses and treatment choices and support the training of students.
Novel functions of Tribbles-homolog 1 in liver, adipocytes and atherosclerosis
Authors: Hernandez-Resendiz Ileana , Burkhardt Ralph
Published: January 2024

Purpose of review

Human genetics studies have sparked great interest in the pseudokinase Tribbles homolog 1, as variant at the TRIB1 gene locus were robustly linked to several cardiometabolic traits, including plasma lipids and coronary artery disease. In this review, we summarize recent findings from mouse models that investigated the function of hepatic and adipocyte Trib1 in lipid metabolism and its role in atherosclerosis.

Recent findings

Studies in atherosclerosis prone low-density lipoprotein (LDL)-receptor knockout mice suggested that systemic Trib1-deficiency promotes atherosclerotic lesion formation through the modulation of plasma lipids and inflammation. Further, investigations in mice with hepatocyte specific deletion of Trib1 identified a novel role in the catabolism of apoB-containing lipoproteins via regulation of the LDL-receptor. Moreover, recent studies on Trib1 in adipocytes uncovered critical functions in adipose tissue biology, including the regulation of plasma lipid and adiponectin levels and the response to β3-adrenergic receptor activation.

Functional studies in mice have expanded our understanding of how Trib1 contributes to various aspects of cardiometabolic diseases. They support the notion that Trib1 exerts tissue-specific effects, which can result in opposing effects on cardiometabolic traits. Additional studies are required to fully elucidate the molecular mechanisms underlying the cellular and systemic effects of Trib1.
Urine CXCL10 as a biomarker in kidney transplantation
Authors: Hirt-Minkowski Patricia , Schaub Stefan
Published: January 2024

Purpose of review

Urine CXCL10 is a promising biomarker for posttransplant renal allograft monitoring but is currently not widely used for clinical management.

Recent findings

Large retrospective studies and data from a prospective randomized trial as well as a prospective cohort study demonstrate that low urine CXCL10 levels are associated with a low risk of rejection and can exclude BK polyomavirus replication with high certainty. Urine CXCL10 can either be used as part of a multiparameter based risk assessment tool, or as an individual biomarker taking relevant confounders into account. A novel Luminex-based CXCL10 assay has been validated in a multicenter study, and proved to be robust, reproducible, and accurate.

Urine CXCL10 is a well characterized inflammation biomarker, which can be used to guide performance of surveillance biopsies. Wide implementation into clinical practice depends on the availability of inexpensive, thoroughly validated assays with approval from regulatory authorities.
Perspectives of Adolescents and Young Adults With Sickle Cell Disease and Clinicians on Improving Transition Readiness With a Video Game Intervention
Authors: Aronson Paul L. , Nolan Sarah A. , Schaeffer Paula , Hieftje Kimberly D. , Ponce Kortney A. , Calhoun Cecelia L.
Published: January 2024

We aimed to learn the experiences of clinicians and adolescents and young adults with sickle cell disease (AYA-SCD) with managing their disease at home and making medical decisions as they transition from pediatric to adult care, and their perceptions of a video game intervention to positively impact these skills. We conducted individual, semistructured interviews with patients (AYA-SCD ages 15 to 26 years) and clinicians who provide care to AYA-SCD at an urban, quaternary-care hospital. Interviews elicited patients’ and clinicians’ experiences with AYA-SCD, barriers and facilitators to successful home management, and their perspectives on shared decision-making and a video game intervention. To identify themes, we conducted an inductive analysis until data saturation was reached. Participants (16 patients and 21 clinicians) identified 4 main themes: (1) self-efficacy as a critical skill for a successful transition from pediatric to adult care, (2) the importance of patient engagement in making medical decisions, (3) multilevel determinants of optimal self-efficacy and patient engagement, and (4) support for a video game intervention which, by targeting potential determinants of AYA-SCD achieving optimal self-efficacy and engagement in decision-making, may improve these important skills.
Characterization of the Use and Efficacy of Isavuconazonium Sulfate in a Pediatric Oncology and Stem Cell Transplant Population: A Single Institution Retrospective Review
Authors: Kunvarjee Binni , Siver Molly , Mathew Sherry , Steiger Samantha , Lee Yeon Joo , Spitzer Barbara
Published: January 2024

Isavuconazonium sulfate (ISA) is a triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis in adults. This single-center, retrospective review of pediatric oncology and stem cell transplant patients receiving ISA for prophylaxis (n=20) or treatment (n=6) of invasive fungal disease (IFD) aims to characterize real-world clinical efficacy and toxicity of ISA in patients <18 years of age. Of 20 patients receiving ISA for prophylaxis, three patients had presumed breakthrough IFD (1 proven, 2 probable/possible). No adverse effects were attributed to ISA use or led to the discontinuation of therapy.
Eating Behavior, Nutritional Status, and Taste Perception Alteration in Children with Cancer
Authors: Fistikçi Yasemin , Bilsin Kocamaz Elif
Published: January 2024

The aim of this study was to investigate eating behavior, nutritional status, and taste alterations in children with cancer. The population of the study consisted of children 8 to 18 years of age and their parents who were followed up and received chemotherapy in the pediatric hematology and oncology clinic and outpatient clinic of a University Faculty of Medicine Oncology Hospital. Data were collected using the Child Identification Form, the Children’s Eating Behavior Questionnaire (CEBQ), the Taste Alteration Scale for Children Receiving Chemotherapy (TAC-TAS), and the Subjective Total Taste Acuity Scale (STTA). Body Mass Index (BMI) Z score was between −2 and +2 (normal) in 92.5% of the children and below ≤−2 (malnutrition) in 7.5%. The mean CEBQ subdimensions scores were food craving 12.48±5.36, emotional overeating 5.28±1.45, enjoyment of food 16.83±5.41, passion for drinking 9.72±5.13, satiety enthusiasm 22.93±6.65, slow eating 9.81±4.95, emotional undereating 16.38±4.41, and food selectivity 10.72±2.86, and the mean total TAC-TAS score was 8.66±10.22. A negative, moderate correlation was determined between food craving and enjoyment of food and taste alteration, with food craving and enjoyment decreasing as food alteration increased. A positive moderate correlation was observed between slow eating and taste alteration, with eating slowing down as taste alteration increased.
Genome sequence of the bialaphos producer Streptomyces sp. DSM 41527 and two putative phosphonate antibiotic producers Streptomyces sp. DSM 41014 and DSM 41981 from the DSMZ strain collection
Authors: Zimmermann Alina , Nouioui Imen , Mast Yvonne
Published: January 2024

Streptomyces sp. DSM 41014, DSM 41527, and DSM 41981 are three strains from the DSMZ strain collection. Here, we present the draft genome sequences of DSM 41014, DSM 41527, and DSM 41981 with a size of 9.09 Mb, 8,45 Mb, and 9,23 Mb, respectively.
Restraint Validation of Biomolecular Structures Determined by NMR in the Protein Data Bank
Authors: Baskaran Kumaran , Ploskon Eliza , Tejero Roberto , Yokochi Masashi , Harrus Deborah , Liang Yuhe , Peisach Ezra , Persikova Irina , Ramelot Theresa A. , Sekharan Monica , Tolchard James , Westbrook John D. , Bardiaux Benjamin , Schwieters Charles D. , Patwardhan Ardan , Velankar Sameer , Burley Stephen K. , Kurisu Genji , Hoch Jeffrey C. , Montelione Gaetano T. , Vuister Geerten W. , Young Jasmine Y.
Published: January 2024

Biomolecular structure analysis from experimental NMR studies generally relies on restraints derived from a combination of experimental and knowledge-based data. A challenge for the structural biology community has been a lack of standards for representing these restraints, preventing the establishment of uniform methods of model-vs-data structure validation against restraints and limiting interoperability between restraint-based structure modeling programs. The NMR exchange (NEF) and NMR-STAR formats provide a standardized approach for representing commonly used NMR restraints. Using these restraint formats, a standardized validation system for assessing structural models of biopolymers against restraints has been developed and implemented in the wwPDB OneDep data deposition-validation-biocuration system. The resulting wwPDB Restraint Violation Report provides a model vs. data assessment of biomolecule structures determined using distance and dihedral restraints, with extensions to other restraint types currently being implemented. These tools are useful for assessing NMR models, as well as for assessing biomolecular structure predictions based on distance restraints.

Graphical Abstract

Highlights

PDB Structure Validation Report expanded to include Restraint Analysis

NMR Exchange Format (NEF) and NMR-STAR for distance restraint representation

Standard distance and dihedral restraint formats for model vs. restraint assessment

Standardized restraint formats provide interoperability between modeling programs
BSAlign: a library for nucleotide sequence alignment
Authors: Shao Haojing , Ruan Jue
Published: January 2024

Increasing the accuracy of the nucleotide sequence alignment is an essential issue in genomics research. Although classic dynamic-programming algorithms (e.g., Smith-Waterman and Needleman–Wunsch) guarantee to produce the optimal result, their time complexity hinders the application of large-scale sequence alignment. Many optimization efforts that aim to accelerate the alignment process generally come from three perspectives: re-designing data structures (e.g., diagonal or striped Single Instruction Multiple Data (SIMD) implementations), increasing the number of parallelisms in SIMD operations (e.g., difference recurrence relation), or reducing searching space (e.g., banded dynamic programming). However, no methods combine all these three aspects to build an ultra-fast algorithm. We have developed a Banded Striped Aligner(library) named BSAlign that delivers accurate alignment results at an ultra-fast speed by knitting a series of novel methods together to take advantage of all of the aforementioned three perspectives with highlights such as active F-loop in striped vectorization and striped move in banded dynamic programming. We applied our new acceleration design on both regular and edit-distance pairwise alignment. BSAlign achieved 2-fold speed-up than other SIMD based implementations for regular pairwise alignment, and 1.5 to 4-fold speedup in edit distance based implementations for long reads. BSAlign is implemented in C programing language and is available athttps://github.com/ruanjue/bsalign.
Diabetes Advances Cardiomyocyte Senescence through miR-103a-3p/Rnd3/STAT3 Signaling
Authors: Wu Linxu , Zhu Xinglin , Luo Cai , Chen Yan , Liu Yin , Zhao Yangyang , Pan Shanshan , Shi Kaijia , Xing Jingci , Lin Xuebin , Qiu Jianmin , Zhang Shuya , Chai Jinxuan , Shen Zhihua , Jie Wei , Guo Junli
Published: January 2024

BACKGROUND

Rnd3, a small Rho-GTPase, is involved in various cardiovascular diseases, but its role in diabetes-induced cardiomyocyte senescence is unclear. This study aims to investigate the role of Rnd3 in cardiomyocyte senescence in diabetes cardiomyopathy (DCM).

METHODS

Rnd3expression was assessed in human tissue using qPCR, and its correlation with clinical parameters was analyzed.Rnd3and Senescence-associated secretory phenotype (SASP)-related marker expression was determined in heart tissue from juvenile/mature mice and streptozotocin-induced diabetic Sprague–Dawley rats. H9C2 and AC16 cardiomyocytes were exposed to high glucose ([HG] =35 mmol/L D-glucose), and Rnd3 and SASP-related marker expression was examined.Rnd3expression in H9C2 cells was disrupted using CRISPR/Cas9 technology, and cellular senescence of HG-treated H9C2 cells was evaluated. MicroRNA sequencing was conducted on AC16 cells to identify differentially expressed microRNAs regulated by HG. Among these microRNAs, miR-103a-3p was selected for further investigation in a clinical diabetes cohort and to examine its binding toRnd33′UTR and its effect on cell senescence. Finally, the role of interaction of Rnd3 and STAT3 in cardiomyocyte senescence was investigated.

RESULTS

Rnd3mRNA levels were reduced in peripheral blood mononuclear cells in diabetic patients, which was negatively correlated to patients age but positively correlated to cardiac function. Older mice exhibited compromised cardiac function, increased SA-β-gal-positive cells, and SASP marker levels versus younger mice. HG stimulation inhibited Rnd3 expression but enhanced cellular senescence.Rnd3knockout resulted in greater cellular senescence on HG-insulted cardiomyocytes. miR-103a-3p was identified as a key HG-regulated microRNA that binds toRnd33′UTR. AAV9 carrying miR-103a-3p sponges andRnd3-overexpressing plasmids mitigated cellular senescence in diabetic rats. Interestingly, miR-103a-3p levels positively correlated with blood glucose concentrations. HG stimulation amplified phosphorylated STAT3(Tyr705) in H9C2 cells, which was intensified byRnd3knockout. Rnd3 binds with STAT3 in cytoplasm and promote proteasome-induced ubiquitination of STAT3. S3I-201 mitigated HG-activated STAT3 and cardiomyocyte senescence.

CONCLUSION

Diabetes causes cardiomyocyte senescence through miR-103a-3p/Rnd3/STAT3 signaling, suggesting a potential treatment strategy for DCM.
Validation ofInternational Classification of Diseases, 10thEdition, Clinical Modification (ICD-10-CM)Code I68.0 for Cerebral Amyloid Angiopathy
Authors: Bruce Samuel S. , Murthy Santosh , Kamel Hooman
Published: January 2024

Introduction

Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage and cognitive impairment in the elderly. Though definitive diagnosis requires post-mortem pathological analysis, clinical and radiographic criteria allow for noninvasive, in vivo diagnosis. We sought to validate the new ICD-10-CM diagnostic code for CAA with respect to the recently updated Boston criteria, version 2.0.

Methods

We conducted a retrospective study of inpatient and outpatient encounters at a single hospital center, Weill Cornell Medicine (WCM), from 10/1/2015 to 12/31/2018. We randomly selected 25 encounters with the ICD-10-CM code I68.0 and 25 encounters with a primary diagnosis of intracerebral hemorrhage or ischemic stroke, without code I68.0. A single board-certified neurologist, blinded to ICD codes, reviewed detailed medical records and images from brain MRI and CT scans from all 50 selected encounters and identified subjects with possible or probable CAA by Boston criteria 2.0. Sensitivity and specificity of ICD-10-CM code I68.0 was calculated.

Results

Of the 50 selected encounters, 21 (42%) met criteria for possible or probable CAA: 18 (36%) met criteria for probable CAA, 2 (4%) met criteria for probable CAA with supporting pathology, and 1 (2%) met criteria for possible CAA. The ICD-10-CM code I68.0 was found to have a sensitivity of 81% (95% CI, 58-95%) and specificity of 72% (95% CI, 53-87%) for identifying possible or probable CAA.

Conclusion

The ICD-10-CM code I68.0 was found to have good sensitivity and moderate specificity for CAA as defined by current clinical and radiographic diagnostic criteria. Based on our results, this code may be useful for identifying patients with CAA in future research using administrative claims data.
Conservation of symbiotic signalling across 450 million years of plant evolution
Authors: Vernié Tatiana , Rich Mélanie , Pellen Tifenn , Teyssier Eve , Garrigues Vincent , Chauderon Lucie , Medioni Lauréna , van Beveren Fabian , Libourel Cyril , Keller Jean , Girou Camille , Lefort Corinne , Le Ru Aurélie , Reinhardt Didier , Kodama Kyoichi , Shimazaki Syota , Morel Patrice , Kyozuka Junko , Mbengue Malick , Vandenbussche Michiel , Delaux Pierre-Marc
Published: January 2024

Highlight

The common symbiotic pathway is activated during arbuscular mycorrhizal symbiosis inMarchantia paleacea

The three core members of the common symbiotic pathway are essential for symbiosis inMarchantia paleacea

The molecular function of the CCaMK/CYCLOPS module is conserved across land plants

Symbiotic signalling has been conserved in plants for 450 million years

The colonization of land by plants 450 million years ago revolutionized life on Earth1. The fossil record2and genetic evidence in extant species3suggest that this transition was facilitated by interactions with symbiotic arbuscular mycorrhizal (AM) fungi4. This ancestral symbiosis relied on the biosynthesis of chemicals by the host plant, both as signals5and as nutrients3. In angiosperms, a signalling pathway involving the receptor-like kinase SYMRK/DMI26,7, the Calcium and Calmodulin-dependent protein kinase CCaMK/DMI38and the transcription factor CYCLOPS/IPD39,10has been described as the common symbiosis pathway (CSP), essential for the establishment of the AM symbiosis and the root-nodule symbiosis11. Phylogenetic and comparative phylogenomic analyses indicated an ancient origin of the CSP, present in all extant land plants forming intracellular symbioses12–15. Trans-complementation assays of the angiosperm mutants with orthologs from diverse species further indicated the conservation of the molecular function of the CSP across the embryophytes9,12,14–16. However, this correlative evidence did not allow testing the ancestral biological function of the CSP. In this study we demonstrate that SYMRK, CCaMK and CYCLOPS are essential for the colonization by AM fungi in bryophytes, indicating that plants have maintained a dedicated signalling pathway to support symbiotic interactions for 450 million years.
Discrete and conserved inflammatory signatures drive thrombosis in different organs afterSalmonellainfection
Authors: Perez-Toledo Marisol , Beristain-Covarrubias Nonantzin , Pillaye Jamie , Persaud Ruby R , Marcial-Juarez Edith , Jossi Sian E. , Hitchcock Jessica R. , Alshayea Areej , Channell William M. , Lamerton Rachel E , Kavanagh Dean P , Carestia Agostina , Horsnell William G , Henderson Ian R. , Mackman Nigel , Clark Andrew R , Jenne Craig N , Rayes Julie , Watson Steve P. , Cunningham Adam F.
Published: January 2024

Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused bySalmonellaTyphimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raises significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-γ or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNFα, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impair thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.
LysM-RLK plays an ancestral symbiotic function in plants
Authors: Teyssier Eve , Grat Sabine , Landry David , Ouradou Mathilde , Rich Melanie K. , Fort Sebastien , Keller Jean , Lefebvre Benoit , Delaux Pierre-Marc , Mbengue Malick
Published: January 2024

Arbuscular mycorrhiza (AM) with soilborne Glomeromycota fungi was pivotal in the conquest of land by plants almost half a billion years ago. In flowering plants, it is hypothesised that AM is initiated by the perception of AM-fungi-derived chito- and lipochito-oligosaccharides (COs/LCOs) in the host via Lysin Motif Receptor-Like Kinases (LysM-RLKs). However, it remains uncertain whether plant perception of these molecules is a prerequisite for AM establishment and for its origin. Here, we made use of the reduced LysM-RLK complement present in the liverwortMarchantia paleaceato assess the conservation of the role played by this class of receptors during AM and in COs/LCOs perception. Our reverse genetic approach demonstrates the critical function of a single LysM-RLK, LYKa, in AM formation, thereby supporting an ancestral function for this receptor in symbiosis. Binding studies, cytosolic calcium variation recordings and genome-wide transcriptomics indicate that another LysM-RLK ofM. paleacea, LYR, is also required for triggering a response to COs/LCOs, despite being dispensable for AM formation. Collectively, our results demonstrate that the perception of symbionts by LysM-RLK is an ancestral feature in land plants, and suggest the existence of yet-uncharacterised AM-fungi signals.
Polymeric nanoparticles delivery of AMPK activator 991 prevents its toxicity and improves muscle homeostasis in Duchenne Muscular Dystrophy
Authors: Andreana Ilaria , Kneppers Anita , Larbi Sabrina Ben , Tifni Federica , Fessard Aurélie , Sidi-Boumedine Jaqueline , Kryza David , Stella Barbara , Arpicco Silvia , Bordes Claire , Chevalier Yves , Chazaud Bénédicte , Mounier Rémi , Lollo Giovanna , Juban Gaëtan
Published: January 2024

Muscular dystrophies, such as Duchenne muscular dystrophy (DMD), are caused by permanent muscle injuries leading to chronic inflammation. In that context, macrophages harbor an altered inflammatory profile that contributes to fibrosis through the secretion of the profibrotic cytokine TGFβ1. We previously showed that AMP-activated protein kinase (AMPK) activation reduces TGFβ1 secretion by macrophages and improves muscle homeostasis and muscle force in a mouse model of DMD. This makes AMPK an attractive therapeutic target for treating chronic inflammation and fibrosis in DMD. However, potent direct AMPK activators like compound 991 show strong adverse effectsin vivo,preventing their direct use. Here, we encapsulated 991 into biodegradable polymeric poly(lactic-co-glycolic) acid (PLGA) nanoparticles forin vivodelivery, in an attempt to overcome toxicity issues. We show that 991-loaded PLGA nanoparticles retained drug activity on fibrotic macrophagesin vitro, by reducing their secretion of TGFβ1. In the D2-mdx pre-clinical DMD mouse model, intravenously injected PLGA nanoparticles reached gastrocnemius and diaphragm muscles, which are the most affected muscles in this model. Chronic intravenous injections of 991-loaded PLGA nanoparticles decreased inflammation in both muscles, which was associated with fibrosis reduction and increase in myofiber size and muscle mass in the gastrocnemius. No impact on blood cell counts and liver enzymes was observed. These results demonstrate that nanomedicine is an efficient strategy to deliver AMPK activatorsin vivoto target inflammation and improve the dystrophic muscle phenotype.
Wellness in work - supporting people in work and assisting people to return to the workforce: An economic evidence review
Authors: Edwards Rhiannon Tudor , Spencer Llinos Haf , Anthony Bethany Fern , Davies Jacob , Pisavadia Kalpa , Makanjuola Abraham , Lloyd-Williams Huw , Fitzsimmons Deborah , Collins Brendan , Charles Joanna Mary , Lewis Ruth , Cooper Alison , Barutcu Sezen , McKibben Mary-Ann , Edwards Adrian
Published: January 2024

Rapid review methodology was used to identify updated economic evidence on programmes or interventions designed to enable employees to remain in and return to the workforce. In Wales, there are currently 1.48 million people in employment and 58,300 people who are unemployed. This equates to an unemployment rate of 3.8% in Wales.

The evidence in this report builds on a previousWellness in Workreport (Edwards et al., 2019). This review has a broad focus to understand the economic impact of well-being within the workplace. The main section of the report is on the economic benefits of keeping the workforce well. Seventy-six papers were included from databases searched for literature published between 2017 and 2023.

Economics studies were found relating to common mental health conditions; severe mental health conditions; influenza vaccination; illicit drug use; smoking and vaping; healthy eating and physical activity. A range of economic evidence of low, medium, and high quality relating to interventions targeting well-being in the workforce was identified. This included high quality evidence that interventions in the workforce for employees at risk of common mental health disorders can be cost saving for businesses and the health and social care sector. There is also high quality evidence on the cost-effectiveness of interventions focusing on healthy eating and physical activity in the workplace. Some evidence gaps were also identified.

Policy and practice implications:There is a need to consider the evidence presented in this rapid review on cost-effective interventions to improve the wellness of the workforce in Wales. Updated policies and procedures to improve equal employment opportunities, regardless of age, gender, or disability status are needed.

Economic considerations:Amongst the G7 nations, the United Kingdom (UK) is performing relatively poorly in relation to returning to pre-pandemic employment rates. This is in part caused by the long elective (planned) surgery waiting lists present in the National Health Service (NHS) right across the UK, highlighting the circular relationship between health and the economy.

Funding statement:The Centre for Health Economics and Medicines Evaluation, the Bangor Institute for Medical and Health Research, and the Swansea Centre for Health Economics were funded for this work by the Health and Care Research Wales Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Re-Irradiation of Recurrent Head and Neck Cancers Using Pulsed Reduced Dose Rate Radiotherapy: An Institutional Series
Authors: Megahed Romy , Prabhu Arpan V. , Mack Delanie P. , Gholami Somayeh , Samanta Santanu , Patel Mausam , Lewis Gary D.
Published: January 2024

Purpose/Objective(s)

Pulsed reduced dose rate (PRDR) radiation (RT) is a re-irradiation (Re-RT) technique that potentially overcomes dose/volume constraints in the setting of previous radiation therapy. While the use of this Re-RT technique has been reported for other disease sites, there is minimal data for its use for recurrent or secondary primary squamous cell carcinoma of the head and neck (HNSCC). In this study, we report preliminary data from our institution of a consecutive cohort of patients with HNSCC who received PRDR Re-RT.

Materials/Methods

Out of 11 patients who received PRDR Re-RT from August 2020 to January 2023, 9 had analyzable data. Intensity modulated RT was used for treatment delivery using either volume modulated arc therapy or helical tomotherapy. A wait time between 20cGy arc/helical deliveries was used to achieve the effective low dose rate. Data collected included patient demographic information, prior interventions, diagnosis, radiation therapy dose and fractionation, progression free survival, overall survival, and toxicity rates.

Results

The median time to PRDR from completion of initial RT was 13 months (range, 6-50 months). All but one patient underwent salvage surgery prior to PRDR. In total, 4 patients received systemic therapy as part of their re-treatment courses. The median follow-up after Re-RT was 7 months. The median OS from PRDR was 7 months (range, 1-32 months). Median PFS was 7 months (range, 1-32 months). One patient (11.1%) had acute grade 3 toxicity, and two patients (22.2%) had late grade 3 toxicities. There were no acute or late grade 4 or 5 toxicities.

Conclusion

PRDR for Re-RT is a feasible treatment strategy for patients with recurrent or second primary HNSCC. Initial findings from this retrospective review suggest reasonable survival outcomes and potentially improved toxicity; prospective data is needed to establish the safety and efficacy of this technique.
A genome-wide meta-analysis of palmoplantar pustulosis implicates Th2 responses and cigarette smoking in disease pathogenesis
Authors: Hernandez-Cordero Ariana , Thomas Laurent , Smail Alice , Lim Zhao Qin , Saklatvala Jake R , Chung Raymond , Curtis Charles J , Baum Patrick , Visvanathan Sudha , Burden A David , Cooper Hywel L , Dunnill Giles , Griffiths Christopher EM , Levell Nick J , Parslew Richard , Reynolds Nick J , Wahie Shyamal , Warren Richard B , Wright Andrew ,   The APRICOT and PLUM Study Team, Simpson Michael , Hveem Kristian , Barker Jonathan N , Dand Nick , Loset Mari , Smith Catherine H , Capon Francesca
Published: January 2024

Background

Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. While the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets.

Objectives

To identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis.

Methods

We performed a genome-wide association meta-analysis of three North-European cohorts (n=1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the resulting association signals. We undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP.

Results

We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with theFCGR3A/FCGR3BandCCHCR1loci. We also observed 13 suggestive (P<5X10-6) susceptibility regions, including theIL4/IL13interval. Accordingly, we demonstrated a significant genetic correlation between PPP and Th2-mediated diseases like atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and enriched for T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP.

Conclusions

The first genome-wide association study of PPP points to a pathogenic role for deregulated Th2 responses and cigarette smoking.

Clinical implications

The results of the first PPP GWAS support the therapeutic potential of agents that inhibit Th2 responses and target inflammatory pathways activated by cigarette smoking.

Capsule

The genetic analysis of ∼1,400 PPP cases and 400,000 healthy controls points to a causal role of abnormal Th2 responses and cigarette smoking. This supports the therapeutic utility of Th2 inhibition.
Factors contributing to immunization coverage among children less than 5 years in Nadowli-Kaleo District of Upper West Region, Ghana
Authors: Kuuyi Alice , Kogi Robert
Published: January 2024

Immunization is believed to prevent deaths from diseases such as diphtheria, tetanus, whooping cough and measles in about 2.5 million children each year worldwide. Failure to vaccinate children in the required timeframe could result in disease outbreaks and increased costs. This study was to identify the causes of low vaccination coverage among children in Nadowli-Kaleo district, Ghana.

An analytical cross-sectional study was adopted for this study. Three hundred and thirty-six participants (336) were recruited through a systematic sampling method. Data was collected using KoboCollect online data collection tool. Data was analyzed using Stata Version 17.0. Chi-square test was used to establish a link between the child’s immunization status and the independent variables. Finally, logistic regression was used to determine the degree of association. To determine statistical significance, a p-value of less than 0.05 at the 95 percent confidence level was employed.

It was revealed that immunization status among children under-five was a little above average (55.4%). Factors that were significantly associated with child full immunization were mother’s or caregiver’s age, marital status, occupation, and current child’s birth order (p-value < 0.05). Other location-related factors significantly associated with full immunization of children were number of ANC visits, delivery location, and distance to health facility. Giving birth to a child at the health facility had higher chance of 2.12 times to be fully immunized than giving birth at home [AOR (95%CI) p-value=2.12 (1.14-3.94)0.017]. The health system related factors which were found to be statistically associated with child full immunization included time spent during immunization service and being informed when to come for the next vaccination.

Immunization coverage is not very encouraging at our study site. To enhance childhood vaccination rates, we suggest expanding access to health services, institutional childbirth, and timely regular antenatal visits.