bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS
Authors: Wang Qiong , Pang Bo , Wu Jing , Li Chunyan , Niu Wenquan
Published: April 2024

Background

Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014–2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years.

Methods

The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects.

Results

Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0–1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714–0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027–1.357). Age at menarche of 16–18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749–0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006–1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values.

Conclusions

Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.
The disruptive role of LRG1 on the vasculature and perivascular microenvironment
Authors: Dritsoula Athina , Camilli Carlotta , Moss Stephen E. , Greenwood John
Published: April 2024

The establishment of new blood vessels, and their subsequent stabilization, is a critical process that facilitates tissue growth and organ development. Once established, vessels need to diversify to meet the specific needs of the local tissue and to maintain homeostasis. These processes are tightly regulated and fundamental to normal vessel and tissue function. The mechanisms that orchestrate angiogenesis and vessel maturation have been widely studied, with signaling crosstalk between endothelium and perivascular cells being identified as an essential component. In disease, however, new vessels develop abnormally, and existing vessels lose their specialization and function, which invariably contributes to disease progression. Despite considerable research into the vasculopathic mechanisms in disease, our knowledge remains incomplete. Accordingly, the identification of angiocrine and angiopathic molecules secreted by cells within the vascular microenvironment, and their effect on vessel behaviour, remains a major research objective. Over the last decade the secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1), has emerged as a significant vasculopathic molecule, stimulating defective angiogenesis, and destabilizing the existing vasculature mainly, but not uniquely, by altering both canonical and non-canonical TGF-β signaling in a highly cell and context dependent manner. Whilst LRG1 does not possess any overt homeostatic role in vessel development and maintenance, growing evidence provides a compelling case for LRG1 playing a pleiotropic role in disrupting the vasculature in many disease settings. Thus, LRG1 has now been reported to damage vessels in various disorders including cancer, diabetes, chronic kidney disease, ocular disease, and lung disease and the signaling processes that drive this dysfunction are being defined. Moreover, therapeutic targeting of LRG1 has been widely proposed to re-establish a quiescent endothelium and normalized vasculature. In this review, we consider the current status of our understanding of the role of LRG1 in vascular pathology, and its potential as a therapeutic target.
Examining the effects of prekindergarten to second grade classroom quality on early elementary achievement
Authors: Kara Yusuf , Farmer Dylan E. , Wright Annie , Kamata Akihito , Hujar Julia , Baker Scott K.
Published: April 2024

Previous research has investigated the influence of preschool interventions in early elementary environments with some results suggesting that high quality early preschool experiences may have meaningful effects on student academic outcomes not only immediately following the preschool years but also in the long term. This study aimed to investigate this topic further by using a novel cross-classified model to account for the complex hierarchical structure of a large-scale longitudinal and multilevel dataset. First, we examined the carryover classroom effects from prekindergarten (PK), kindergarten (K), and first grade on later grades’ reading and mathematics scores. Second, we explored the effect of PK to second grade classroom quality on students’ K, first, and second grade reading and mathematics scores. Our analyses yielded significant PK carryover classroom effects for reading; these results provide evidence that a student’s PK classroom continues to impact that student for at least three years after. Additionally, one domain of PK classroom quality —classroom organization—was found to be positively related to students’ K, first, and second grade reading outcomes.
The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism
Authors: Jiang Yiran , Zhou Lihua , Zhang Cui , Su Tingwei , Jiang Lei , Zhou Weiwei , Zhong Xu , Wu Luming , Wang Weiqing
Published: April 2024

Context

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically.

Objective

To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population.

Design

Retrospective cohort study.

Methods

We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion.

Results

UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0–120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery.

Conclusions

UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.
Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats
Authors: Zhang Qing-zheng , Zhang Ji-rui , Li Xue , Yin Jin-long , Jin Li-ming , Xun Zhuo-ran , Xue Hao , Yang Wan-qi , Zhang Hua , Qu Jingyong , Xing Zhi-kai , Wang Xu-min
Published: April 2024

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.
A two-dose viral-vectored Plasmodium vivax multistage vaccine confers durable protection and transmission-blockade in a pre-clinical study
Authors: Yamamoto Yutaro , Fabbri Camila , Okuhara Daiki , Takagi Rina , Kawabata Yuna , Katayama Takuto , Iyori Mitsuhiro , Hasyim Ammar A. , Sakamoto Akihiko , Mizukami Hiroaki , Shida Hisatoshi , Lopes Stefanie , Yoshida Shigeto
Published: April 2024

Among Plasmodium spp. responsible for human malaria, Plasmodium vivax ranks as the second most prevalent and has the widest geographical range; however, vaccine development has lagged behind that of Plasmodium falciparum, the deadliest Plasmodium species. Recently, we developed a multistage vaccine for P. falciparum based on a heterologous prime-boost immunization regimen utilizing the attenuated vaccinia virus strain LC16m8Δ (m8Δ)-prime and adeno-associated virus type 1 (AAV1)-boost, and demonstrated 100% protection and more than 95% transmission-blocking (TB) activity in the mouse model. In this study, we report the feasibility and versatility of this vaccine platform as a P. vivax multistage vaccine, which can provide 100% sterile protection against sporozoite challenge and >95% TB efficacy in the mouse model. Our vaccine comprises m8Δ and AAV1 viral vectors, both harboring the gene encoding two P. vivax circumsporozoite (PvCSP) protein alleles (VK210; PvCSP-Sal and VK247; -PNG) and P25 (Pvs25) expressed as a Pvs25–PvCSP fusion protein. For protective efficacy, the heterologous m8Δ-prime/AAV1-boost immunization regimen showed 100% (short-term; Day 28) and 60% (long-term; Day 242) protection against PvCSP VK210 transgenic Plasmodium berghei sporozoites. For TB efficacy, mouse sera immunized with the vaccine formulation showed >75% TB activity and >95% transmission reduction activity by a direct membrane feeding assay using P. vivax isolates in blood from an infected patient from the Brazilian Amazon region. These findings provide proof-of-concept that the m8Δ/AAV1 vaccine platform is sufficiently versatile for P. vivax vaccine development. Future studies are needed to evaluate the safety, immunogenicity, vaccine efficacy, and synergistic effects on protection and transmission blockade in a non-human primate model for Phase I trials.
Isolation and characterization of Hc-targeting chimeric heavy chain antibodies neutralizing botulinum neurotoxin type B
Authors: Jiang Yujia , Wang Rong , Guo Jiazheng , Cheng Kexuan , Chen Lei , Wang Xi , Li Yating , Du Peng , Gao Chen , Lu Jiansheng , Yu Yunzhou , Yang Zhixin
Published: April 2024

Background

Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is one of the most potent known toxins. Moreover, BoNT is classified as one of the most important biological warfare agents that threatens the biosafety of the world. Currently, the approved treatment for botulism in humans is the use of polyvalent horse serum antitoxins. However, they are greatly limited because of insufficient supply and adverse reactions. Thus, treatment of human botulism requires the development of effective toxin-neutralizing antibodies. Considering their advantages, neutralizing nanobodies will play an increasing role as BoNTs therapeutics.

Methods

Herein, neutralizing nanobodies binding to the heavy chain (Hc) domain of BoNT/B (BHc) were screened from a phage display library. Then, BoNT/B-specific clones were identified and fused with the human Fc fragment (hFc) to form chimeric heavy chain antibodies. Finally, the affinity, specificity, and neutralizing activity of antibodies against BoNT/B in vivo were evaluated.

Results

The B5-hFc, B9-hFc and B12-hFc antibodies demonstrated high affinity for BHc in the nanomolar range. The three antibodies were proven to have potent neutralizing activity against BoNT/B in vivo.

Conclusion

The results demonstrate that inhibiting toxin binding to the host receptor is an efficient strategy and the three antibodies could be used as candidates for the further development of drugs to prevent and treat botulism.
Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models
Authors: Iwatake Mayumi , Nagamura-Inoue Tokiko , Doi Ryoichiro , Tanoue Yukinori , Ishii Mitsutoshi , Yukawa Hiroshi , Matsumoto Keitaro , Tomoshige Koichi , Nagayasu Takeshi , Tsuchiya Tomoshi
Published: April 2024

Background

Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion.

Objective

To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment.

Methods

dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed.

Results

Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin β1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs.

Conclusion

We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.
Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies
Authors: Shao Chenyi , Xia Nana , Zhen Yan , Zhang Xueliang , Yan Ninghui , Guo Qiang
Published: April 2024

Objectives

Interstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS).

Methods

Here, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately.

Results

Peripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS.

Conclusions

Patients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD
Co-designing an intervention using the COM-B model to change an eating behaviour in people living with achalasia
Authors: Kalantari Melika , Hollywood Amelia , Lim Rosemary , Hashemi Majid
Published: April 2024

Background

Achalasia is a rare motility disorder affecting the oesophagus, leading to difficulties with eating and drinking. Participants in previous studies reported that they needed more social, clinical and behavioural support in the long-term management of achalasia. This study, therefore aimed to 1) identify the most challenging eating behaviour for people living with achalasia and 2) co-design a behaviour change intervention to help address the challenges they experience.

Methods

This study used a qualitative approach involving online focus groups. The COM-B model was the theoretical framework, with behaviour change techniques (BCTs) as the active ingredients that target a mixture of capability, opportunity and/or motivation. Three focus groups were undertaken to obtain a range of input from different people living with achalasia. Participants in this study identified the target behaviour, prioritised the different BCTs which most resonated with them to design an intervention and decided on the mode of delivery. The research team analysed the techniques that helped participants with their eating behaviour using the COM-B model as a framework to create the intervention.

Results

The 24 participants in this study identified “eating in a social setting” as the target behaviour for the intervention. A workbook that can be personalised by the individual was the most suitable intervention. The workbook structure aligns with the constructs of the COM-B model. It includes reflection, activities and goal-setting sections based on what was indicated to be useful for the majority of the participants. Key techniques to overcome the challenges with eating in a social setting included social support, regulation to reduce negative emotions, goals and planning.

Conclusion

Using a focus group approach with the COM-B model as the theoretical framework, the participants in this study developed an intervention to support people living with achalasia. In order to achieve long-term behaviour change, engagement with a personalised workbook could facilitate eating in a social setting. Future work will need to pilot the workbook to ensure it can support people to improve their quality of life and complement the ongoing care they receive from health services.
Optimizing clinical outcomes in polypharmacy through poly-de-prescribing: a longitudinal study
Authors: Garfinkel Doron , Levy Yuval
Published: April 2024

Objectives

To evaluate polypharmacy in older people to determine whether the number of medications de-prescribed correlates with the extent of improvement in quality of life (QoL) and clinical outcomes.

Design

A prospective longitudinal cohort study of polypharmacy in people living in a community in Israel.

Setting

Participants aged 65 years or older who took at least six prescription drugs followed up for at least 3 years (range 3–10 years) after poly-de-prescription (PDP) recommendations.

Interventions

PDP recommended at first home visit using the Garfinkel algorithm. Annual follow-up and end-of-study questionnaires used to assess clinical outcomes, QoL, and satisfaction from de-prescribing. All medications taken, complications, hospitalizations, and mortality recorded. In total, 307 participants met the inclusion criteria; 25 incomplete end-of-study questionnaires meant 282 participants for subjective analysis. Participants divided into two subgroups: (i) those who discontinued more than 50% of the drugs (PDP group) or (ii) those who discontinued less than 50% of the drugs (non-responders, NR).

Main outcome measures

Objective: 3-year survival rate and hospitalizations. Subjective: general satisfaction from de-prescribing; change in functional, mental, and cognitive status; improved sleep quality, appetite, and continence; and decreased pain.

Results

Mean age: 83 years (range 65–99 years). Mean number of drugs at baseline visit: 9.8 (range 6–20); 6.7 ± 2.0 de-prescribed in the PDP group (n = 146) and 2.2 ± 2.1 in the NR group (n = 161) (p < 0.001).

No statistical difference between the groups in the 3-year survival rate and hospitalizations, but a significant improvement in functional and cognitive status and, in general, satisfaction from the intervention in the PDP group compared to the NR group. Improvement usually evident within the first 3 months and persists for several years.

Conclusion

Poly-de-prescribing in the older population has beneficial effects on several clinical outcomes with no detrimental effect on the rate of hospitalization and survival. The extent of improvement correlates with the extent of de-prescribing. Applying the Garfinkel algorithm globally may improve QoL in millions of patients, a clinical and economic win–win situation.
PAM-1: an antimicrobial peptide with promise against ceftazidime-avibactam resistant Escherichia coli infection
Authors: Han Yijia , Zhang Yi , Zhang Xiaodong , Huang Zeyu , Kong Jingchun , Wang Xiuxiu , Chen Lijiang , Wang Yue , Cao Jianming , Zhou Tieli , Shen Mo
Published: April 2024

Introduction

Antibiotic misuse and overuse have led to the emergence of carbapenem-resistant bacteria. The global spread of resistance to the novel antibiotic combination ceftazidime-avibactam (CZA) is becoming a severe problem. Antimicrobial peptide PAM-1 offers a novel approach for treating infections caused by antibiotic-resistant bacteria. This study explores its antibacterial and anti-biofilm activities and mechanisms against CZA-resistant Escherichia. Coli (E. coli), evaluating its stability and biosafety as well.

Methods

The broth microdilution method, growth curve analysis, crystal violet staining, scanning electron microscopy, and propidium iodide staining/N-phenyl-1-naphthylamine uptake experiments were performed to explore the antibacterial action and potential mechanism of PAM-1 against CZA-resistant E. coli. The biosafety in diverse environments of PAM-1 was evaluated by red blood cell hemolysis, and cytotoxicity tests. Its stability was further assessed under different temperatures, serum concentrations, and ionic conditions using the broth microdilution method to determine its minimum inhibitory concentration (MIC). Galleria mellonella infection model and RT-qPCR were used to investigate the in vivo antibacterial and anti-inflammatory effects.

Results and discussion

In vitro antibacterial experiments demonstrated that the MICs of PAM-1 ranged from 2 to 8 μg/mL, with its effectiveness sustained for a duration of 24 h. PAM-1 exhibited significant antibiofilm activities against CZA-resistant E. coli (p < 0.05). Furthermore, Membrane permeability test revealed that PAM-1 may exert its antibacterial effect by disrupting membrane integrity by forming transmembrane pores (p < 0.05). Red blood cell hemolysis and cytotoxicity tests revealed that PAM-1 exerts no adverse effects at experimental concentrations (p < 0.05). Moreover, stability tests revealed its effectiveness in serum and at room temperature. The Galleria mellonella infection model revealed that PAM-1 can significantly improve the survival rate of Galleria mellonella (>50%)for in vivo treatment. Lastly, RT-qPCR revealed that PAM-1 downregulates the expression of inflammatory cytokines (p < 0.05). Overall, our study findings highlight the potential of PAM-1 as a therapeutic agent for CZA-resistant E. coli infections, offering new avenues for research and alternative antimicrobial therapy strategies.
Resident gut microbiota community determines the efficacy of soluble fiber in reducing adiposity
Authors: Shallangwa Swang M. , Ross Alexander W. , Walker Alan W. , Morgan Peter J.
Published: April 2024

Consumption of dietary fiber has been linked to several health benefits. Among these, dietary fiber breakdown through the process of anaerobic fermentation by the colonic microbiota leads to the production of beneficial metabolites, mainly short-chain fatty acids (acetate, propionate, and butyrate), which have been implicated in reduced calorie intake. Nevertheless, the link between gut microbiota and obesity remains unclear. We investigated the effects of dietary fibers on food intake and body weight gain in two independent but similarly designed studies in rats. In the first study, the inclusion of 10% w/w pectin, fructooligosaccharides or beta-glucan (n = 10/group) in the diets each significantly reduced body weight gain (‘responders’) compared to the cellulose control whereas, in a closely matched, but not fully identical study (n = 8/group), no effect of dietary fiber on body weight (‘non-responders’) was observed. The aim of this work was to explore the basis of this differential response between the two similarly designed and comparable studies, with a focus on the potential role of the gut microbiota in the control of food intake and body weight.
MIR4435-2HG as a possible novel predictive biomarker of chemotherapy response and death in pediatric B-cell ALL
Authors: Torres-Llanos Yulieth , Zabaleta Jovanny , Cruz-Rodriguez Nataly , Quijano Sandra , Guzmán Paula Carolina , de los Reyes Iliana , Poveda-Garavito Nathaly , Infante Ana , Lopez-Kleine Liliana , Combita Alba Lucía
Published: April 2024

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-).

Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA sequencing assays were performed on 13 bone marrows from Hispanic children with B-cell ALL. Partek Flow was used for transcript mapping and quantification, followed by differential expression analysis using DEseq2. DNA methylation analyses were performed with Partek Genomic Suite and Genome Studio. Gene expression and differential methylation were compared between patients with MRD−/− and MRD+/+ at the end of induction chemotherapy. Overexpressed and hypomethylated genes were selected and validated by RT-qPCR in samples of an independent validation cohort. The predictive ability of the genes was assessed by logistic regression. Survival and Cox regression analyses were performed to determine the association of genes with death.

Results:DAPK1, BOC, CNKSR3, MIR4435-2HG, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in MRD+/+ patients. Overexpression was also validated by RT-qPCR. DAPK1, BOC, ASCL2, and CNKSR3 can predict refractoriness, but MIR4435-2HG is the best predictor. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. Finally, MIR4435-2HG overexpression, together with MRD+, are associated with poorer survival, and together with overexpression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype.

Conclusion:MIR4435-2HG is a potential predictive biomarker of treatment response and death in children with B-cell ALL.
Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats
Authors: Fauser Mareike , Payonk Jan Philipp , Weber Hanna , Statz Meike , Winter Christine , Hadar Ravit , Appali Revathi , van Rienen Ursula , Brandt Moritz D. , Storch Alexander
Published: April 2024

Introduction

Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson’s disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.

Methods

In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation.

Results

STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches.

Discussion

Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson’s disease.
A study of the impact of staggered boards on corporate financialization: from the perspective of board governance
Authors: Cao Chongyan , Zhang Yutong
Published: April 2024

Introduction

The objective of this study is to assess the influence of staggered boards on corporate financialization and the role that incentive and supervision mechanisms play in this process.

Methods

We employ a total of 20,647 panel data samples of Chinese A-share listed companies over the period 2011-2020 to empirically test the impact of staggered boards on corporate financialization in the Chinese context.

Results

The results indicate that implementing staggered boards significantly increases levels of corporate financialization. On the one hand, the implementation of a staggered board structure can exacerbate the speculative mindset and profit-driven behavior among board members, leading management to prioritize financial investments for personal gain. On the other hand, a staggered board system may also amplify managerial laziness, potentially incentivizing them to rely heavily on financial investments in order to swiftly achieve performance targets with minimal effort. Furthermore, both managerial ownership and audit supervision are found to be critical factors in mitigating this positive impact and preventing excessive financial investment behavior.

Discussion

This paper offers guidance on comprehending the applicability of staggered board provisions and mitigating financial risks in enterprises.
Are cash incentives always king? A randomized controlled trial evaluating hedonic versus cash incentives (TEH-C)
Authors: Finkelstein Eric Andrew , Chow Michelle Tian Nee , Gandhi Mihir
Published: April 2024

Introduction

Physical inactivity is a risk factor for obesity and non-communicable diseases. Despite myriad health and non-health benefits resulting from physical activity (PA), most individuals do not meet PA recommendations. Providing an incentive for meeting activity goals may increase activity levels. Classical economists argue that cash is the best incentive. Behavioral economists have posited that hedonic (pleasurable) incentives (e.g., massages, restaurant meals) may be superior to cash when incentives are offered over multiple time periods. To date, no studies have directly compared the effectiveness of cash versus hedonic incentives in promoting PA across multiple time periods.

Methods

We conducted a two-arm, parallel, 4-month randomized controlled trial with healthy adults in Singapore where participants were randomized to either cash or hedonic incentives. Participants could earn up to SGD50 (≈USD37) in cash or hedonic incentives each month they met the study’s step target of 10,000 steps daily on at least 20/25 days out of the first 28 days of a month. The primary objective was to compare the mean proportion of months that participants met the step target between the two arms.

Results

By month 4, participants in the cash (N = 154) and hedonic incentive (N = 156) arms increased their mean daily steps by 870 (p < 0.001) and 1,000 steps (p < 0.001), respectively. The mean proportion of months the step target was achieved was 90.53 and 88.34 for participants in the cash and hedonic incentive arms respectively, but differences across arms were small and not statistically significant for this or any outcome assessed.

Conclusion

Our findings suggest that both cash and hedonic incentives are effective at promoting physical activity but that neither strategy is clearly superior.

Clinical trial registration: ClinicalTrials.gov, NCT 04618757 registered on November 6, 2020.
Exploring active ageing in a community-based living environment: an ethnographic study in the Western Norway context
Authors: Førsund Elise , Torrado Vidal Juan Carlos , Fæø Stein Erik , Reithe Haakon , Patrascu Monica , Husebo Bettina S.
Published: April 2024

Background

Age-friendly environments intend to promote active ageing by facilitating social, mental, and physical participation. This could potentially delay the onset of chronic complex conditions, enabling people to live longer independently at home, and prevent loneliness. This study investigates a community-based living environment in Norway called Helgetun and aims to explore how it can facilitate active ageing.

Method

We chose an ethnographic approach consisting of observation, informal conversations, and in-depth semi-structured interviews with 15 residents (11 female, 4 male, ages 62–84). We analysed the data using reflexive thematic analysis.

Result

We developed three themes on facilitating active ageing in this living environment: maintaining self-identity, experiencing growth and development, and feeling a sense of belonging. These themes were related to physical activity levels, social engagement, and overall satisfaction with the living environment. Maintaining self-identity concerned getting a new role in life as well as access to meaningful activities. Experiencing growth and development involved being exposed to new activities, learning new skills, and experiencing mastery. Lastly, feeling a sense of belonging meant feeling safe and part of a group, as well as receiving social support and help. This feeling of social connectedness and safety was reflected in their experience with the COVID-19 pandemic, in which most felt relatively unaffected, suggesting that this way of living could increase reliance among this age group.

Conclusion

Having a flexible structure, adapting to the core needs and individual resources of the residents, can facilitate active ageing in community-based living environments. Our findings contribute to the growing evidence that these environments increase social and physical engagement, whilst reducing social isolation and loneliness. These findings may be particularly relevant in a Norwegian context—where older adults are less dependent on family for care—and are meant as grounding points for policymakers to reflect upon designing future senior living.
Evaluation of the Co–Go–Me angle as a predictor in Class II patients treated with Herbst appliance and skeletal anchorage: a retrospective cohort study
Authors: Manni Antonio , Migliorati Marco , Boggio Andrea , Drago Sara , Paggi Elena , Calzolari Chiara , Gastaldi Giorgio , Cozzani Mauro
Published: April 2024

Introduction

A condylion–gonion–menton (Co–Go–Me) angle threshold of 125.5° has been introduced as a predictive parameter of cephalometric mandibular response in the orthopedic treatment of growing Class II patients with functional appliances, despite some contradictions in the literature. Considering the lack of studies evaluating the role of skeletal anchorage, this study aims to reassess the threshold of 125.5° in the Co–Go–Me angle as a useful predictor in growing skeletal Class II patients treated with acrylic splint Herbst appliance and two mini-screws in the lower arch (STM2).

Methods

Thirty-five consecutively treated patients (20 males, 15 females; mean age, 11.37 years) with mandibular retrusion were classified into two groups according to their Co–Go–Me baseline values (Group 1, <125.5°; Group 2, >125.5°). The STM2 protocol involved the use of the MTH Herbst appliance with an acrylic splint in the lower arch and two interradicular mini-screws as anchorage reinforcement. Cephalometric analysis was performed by the same operator for each patient at baseline (T0) and at the end of the Herbst phase (T1). The effects of time and group on the variables were assessed by a repeated-measures analysis of variance. The primary research outcome was the difference between the groups in terms of mandibular responsiveness to treatment referred to as the relative difference (T1−T0) in Co_Gn.

Results

The mean duration of the treatment was 9.5 months. No statistically significant differences between groups were detected at baseline, except from the expected SN/GoMe° (p < 0.001) and Co–Go mm (p = 0.028). No statistically significant changes between groups, which were caused by the treatment, were found considering the mandibular sagittal and vertical skeletal parameters. Similarly, no statistically significant differences were found in the dental changes between the high-angle and low-angle patients, apart from the upper molar sagittal position (p = 0.013).

Discussion and conclusions

The 125.5° threshold in the Co–Go–Me value was not a reliable predictive parameter for the mandibular response in growing patients treated with the MTH Herbst appliance and lower skeletal anchorage. Due to its effective control in the sagittal and vertical planes, the STM2 technique might be an appropriate protocol to use in treating skeletal Class II patients, regardless of the growth pattern.
Is there a beneficial effect of a high-protein diet on body composition and strength capacity in physical active middle-aged individuals?—An eight-week randomized controlled trial
Authors: Schalla Jan , Frommelt Sina , Geisler Stephan , Isenmann Eduard
Published: April 2024

Introduction

Demographic changes are resulting in a continual increase in the proportion of individuals over 65 years old. Simultaneously, muscle mass (MM) tends to decrease with age, with a decline noticeable from the middle of the fourth decade of life. While physical activity is considered a modulator for maintaining MM, the interaction with nutrient uptake, especially protein intake, is getting more into focus. Due to a lack of data on the effect of a high-protein diet on middle-aged individuals (40–65 years), this study aimed to investigate the influence of a high-protein diet in middle-aged physically active persons on body composition and performance.

Methods

Using stratified randomization, participants were allocated to either a high-protein group (>2.3 g/kg FFM/day) (n = 12, age = 57.83 ± 7.74 years, height = 170.42 cm ± 11.04 cm, BMI = 30.26 ± 4.46, MM = 31.71 ± 6.89 kg) or a control group (<2.3 g/kg/FFM/day) (n = 14, age = 58.21 ± 6.44 years, height = 170.57 cm ± 8.28 cm, BMI = 26.31 ± 5.59, MM = 29.67 ± 8.08 kg). Body composition [fat-free mass (FFM), fat mass (FM), MM] and strength were assessed at baseline (T0), after four weeks (T1) and after eight weeks (T2). Exercise habits were not changed over the entire period and dietary habits were recorded using FDDB Explorer. Statistical analysis was performed using the current version of R and linear mixed models.

Results

No significant differences in energy intake were found between the groups (p = .974). In macronutrient distribution, a significantly higher consumption of protein was found in the high-protein group (p < .0001, d = 2.22) [140 ± 70 g/day (HPG) vs. 79 ± 40 g/day (CG)]. A trivial reduction in FM over time in both groups (p = .046, d = 0.04, Δt=−.83±1.60kg) was observed. No significant differences were detected in FFM (p = .887) and MM (p = .711). Trivial interaction effects (time*group) were observed for upper (p = .007, d = 0.12, ΔHPG = 4.38 ± 3.25 kg) and lower body strength (p = .0507, d = 0.07, ΔHPG = 3.33 ± 2.36 kg).

Discussion

Our results indicate no to only trivial effects of adding a high-protein diet to otherwise physically active middle-aged individuals. Trivial effects could be seen for an increase in muscle strength after this eight-week intervention. However, MM and FFM were not significantly affected. Based on the small effect sizes we observed in our results we do not see a benefit of a high-protein diet on body composition and strength capacity without altering the exercise habits.
Impact of sustainability integrating environmental and social practices on farm resilience: a quantitative study of farmers facing the post-COVID-19 economic turbulence in Japan
Authors: Yoshida Shingo
Published: April 2024

Research on sustainability practices and resilience in farm systems has focused on the mutual interrelationship between the two. When identifying critical variables related to sustainability, it is essential to take an integrated perspective that considers the interplay among sustainable practices and uses a dataset that includes both environmental and social indicators. Thus, this study aims to quantitatively identify the impact of integrated sustainability indices on farm resilience, which is classified as persistence and adaptation, in the face of Post-COVID-19 economic turbulence. We obtained data from a questionnaire survey of 4,604 farms conducted by a government financial institution. Integrated sustainability indices and resilience indices are formulated through the application of factor analysis. As a result, we develop six sustainability indices that integrate environmental and social practices. A regression analysis reveals a positive correlation between the integrated sustainability indices and short-term persistence as farm resilience. Moreover, these sustainability indices exhibit a more pronounced impact on long-term adaptive resilience. These results imply that the integrated sustainability indices are more adept at evaluating farmers’ sustainability endeavors and clarifying the relationship between sustainability and farm resilience than traditional environmental and social sustainability indicators.
Nurse Staffing, Work Hours, Mandatory Overtime, and Turnover in Acute Care Hospitals Affect Nurse Job Satisfaction, Intent to Leave, and Burnout: A Cross-Sectional Study
Authors: Bae Sung-Heui
Published: April 2024

Objectives: This study examined the impact of nurse staffing, working hours, mandatory overtime, and turnover on nurse outcomes in acute care hospitals. Previous studies have focused on the single characteristics of sub-optimal nurse staffing but have not considered them comprehensively.

Methods: Data were collected in July–September 2022 using convenience sampling and an online survey (N = 397). For the analysis, 264 nurses working as staff nurses at 28 hospitals met the inclusion criteria. Univariate analysis and multivariable generalized estimating equation (GEE) were performed.

Results: Both nurse staffing (β = −0.036, standard error [SE] = 0.011) and turnover (β = −0.006, SE = 0.003) were significant factors affecting job satisfaction. In the multivariable GEE, only mandatory overtime (β = 0.395, SE = 0.116) was significantly related to intent to leave. Nurse staffing, work hours, mandatory overtime, and turnover were not significantly related to burnout. Subjective health status and workload were significantly associated with burnout.

Conclusion: Nurse staffing policies and improvement programs in hospitals should be implemented to improve nurses’ job satisfaction. Labor policy should ban mandatory overtime.
Fresh Insights Into SLC25A26: Potential New Therapeutic Target for Cancers: A Review
Authors: Xu Yangheng , Hong Zhisheng , Yu Sheng , Huang Ronghan , Li Kunqi , Li Ming , Xie Sisi , Zhu Lvyun
Published: April 2024

SLC25A26 is the only known human mitochondrial S-adenosylmethionine carrier encoding gene. Recent studies have shown that SLC25A26 is abnormally expressed in some cancers, such as cervical cancer, low-grade glioma, non-small cell lung cancer, and liver cancer, which suggests SLC25A26 can affect the occurrence and development of some cancers. This article in brief briefly reviewed mitochondrial S-adenosylmethionine carrier in different species and its encoding gene, focused on the association of SLC25A26 aberrant expression and some cancers as well as potential mechanisms, summarized its potential for cancer prognosis, and characteristics of mitochondrial diseases caused by SLC25A26 mutation. Finally, we provide a brief expectation that needs to be further investigated. We speculate that SLC25A26 will be a potential new therapeutic target for some cancers.