bluuebunny/crossref_metadata_2025 huggingface dataset:
Arteriovenous fistula in functional motor disability
Authors: Sarangi Shakti Swarup , Singh Vikram , Bhirud Deepak Prakash , Sandhu Arjun Singh
Published: February 2023

Arteriovenous fistula (AVF) is the preferred route for vascular access in patients with chronic kidney disease on maintenance haemodialysis. Many studies have demonstrated the positive effects of perioperative hand exercise on fistula maturation. Here, we present our experience of radio cephalic AVF creation in patients with neuromuscular disorders who had difficulty performing isometric hand exercises. We created AVF in three patients with neurological disorders. First patient had essential tremor, which created difficulty during hand exercises and surgery while the other two patients had right hemiparesis. Perioperative isometric exercises have been shown to help in maturation of AVF. Due to neurological involvement, our patients had difficulty performing hand exercises. All had successful AVF despite taking longer than usual time to mature. Creation of AVF in neuromuscular diseases is feasible. A preoperative Doppler ultrasound to assess the vessels might help in making an informed decision. This might spare such patients the only functional arm.
PET-positive suture granuloma of abdominal wall 56 years post-appendicectomy mimicking recurrence of lymphoma
Authors: Gaylard Aubrey , Goai Xin Yi , Du Guesclin Alexandra , Hodgson Russell
Published: February 2023

We present a unique case of a positron emission tomography (PET)-positive suture granuloma deep to an appendicectomy abdominal wall scar from 56 years prior in a patient with treated lymphoma. The lesion was first detected 8 years ago on a PET scan for new diagnosis of follicular lymphoma, with stable appearances 6 and 7 years later at follow-up. Ultrasound-guided biopsy and flow cytometry of the specimen could not exclude an untreated or recurrent lymphoma; thus, the patient underwent resection of the right iliac fossa abdominal wall lesion. Histopathology results noted granulomatous inflammation surrounding foreign material. The patient had an uneventful postoperative recovery and was discharged from surgical services. In this paper, we review the current literature and discuss the dilemma involved in the diagnosis and management of suture granulomas.
Examining the Lancet Commission risk factors for dementia using Mendelian randomisation
Authors: Desai Roopal , John Amber , Saunders Rob , Marchant Natalie L , Buckman Joshua E J , Charlesworth Georgina , Zuber Verena , Stott Joshua
Published: February 2023

Background

Dementia incidence is increasing across the globe and currently there are no disease-modifying pharmaceutical treatments. The Lancet Commission on dementia identified 12 modifiable risk factors which explain 40% of dementia incidence. However, whether these associations are causal in nature is unclear.

Objective

To examine the modifiable risk factors for dementia as identified in the Lancet Commission review using Mendelian randomisation (MR) to establish if, based on genetic evidence, these associations with different dementia subtypes are causal in nature.

Methods

Publicly available genome-wide association study data were used for 10 risk factors and Alzheimer’s disease (AD), frontotemporal dementia and dementia with Lewy bodies. Two-sample MR using the inverse varianceweighted method was conducted to test for causal relationships. Weighted median MR and MR-Egger were used to test for pleiotropic effects.

Results

Genetic proxied risk for higher levels of smoking (OR: 0.80 (95% CI: 0.69; 0.92), p=0.002), obesity (OR: 0.87 (95% CI: 0.82; 0.92), p<0.001) and blood pressure (OR: 0.90 (95% CI: 0.82; 0.99), p=0.035) appeared to be protective against the risk of AD. Post hoc analyses indicated these associations had pleiotropic effects with the risk of coronary artery disease. Genetic proxied risk of educational attainment was found to be inconsistently associated with the risk of AD.

Conclusions and implications

Post hoc analysis indicated that the apparent protective effects of smoking, obesity and blood pressure were a result of survivor bias. The findings from this study did not support those presented by the Lancet Commission. Evidence from causal inference studies should be considered alongside evidence from epidemiological studies and incorporated into reviews of the literature.
Implemented machine learning tools to inform decision-making for patient care in hospital settings: a scoping review
Authors: Tricco Andrea C , Hezam Areej , Parker Amanda , Nincic Vera , Harris Charmalee , Fennelly Orna , Thomas Sonia M , Ghassemi Marco , McGowan Jessie , Paprica P Alison , Straus Sharon E
Published: February 2023

Objectives

To identify ML tools in hospital settings and how they were implemented to inform decision-making for patient care through a scoping review. We investigated the following research questions: What ML interventions have been used to inform decision-making for patient care in hospital settings? What strategies have been used to implement these ML interventions?

Design

A scoping review was undertaken. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 2009 until June 2021. Two reviewers screened titles and abstracts, full-text articles, and charted data independently. Conflicts were resolved by another reviewer. Data were summarised descriptively using simple content analysis.

Setting

Hospital setting.

Participant

Any type of clinician caring for any type of patient.

Intervention

Machine learning tools used by clinicians to inform decision-making for patient care, such as AI-based computerised decision support systems or “‘model-based’” decision support systems.

Primary and secondary outcome measures

Patient and study characteristics, as well as intervention characteristics including the type of machine learning tool, implementation strategies, target population. Equity issues were examined with PROGRESS-PLUS criteria.

Results

After screening 17 386 citations and 3474 full-text articles, 20 unique studies and 1 companion report were included. The included articles totalled 82 656 patients and 915 clinicians. Seven studies reported gender and four studies reported PROGRESS-PLUS criteria (race, health insurance, rural/urban). Common implementation strategies for the tools were clinician reminders that integrated ML predictions (44.4%), facilitated relay of clinical information (17.8%) and staff education (15.6%). Common barriers to successful implementation of ML tools were time (11.1%) and reliability (11.1%), and common facilitators were time/efficiency (13.6%) and perceived usefulness (13.6%).

Conclusions

We found limited evidence related to the implementation of ML tools to assist clinicians with patient healthcare decisions in hospital settings. Future research should examine other approaches to integrating ML into hospital clinician decisions related to patient care, and report on PROGRESS-PLUS items.

Funding

Canadian Institutes of Health Research (CIHR) Foundation grant awarded to SES and the CIHR Strategy for Patient Oriented-Research Initiative (GSR-154442).

Scoping review registration

https://osf.io/e2mna.
Fear of falling: scoping review and topic analysis protocol
Authors: Kolpashnikova Kamila , Desai Shital
Published: February 2023

Introduction

Fear of falling (FoF) is a major challenge for the quality of life among older adults. Despite extensive work in previous scoping and systematic reviews on separate domains of FoF and interventions related to FoF, very little attention has been devoted to a comprehensive scoping review mapping the range and scope of this burgeoning area of study, with only a few exceptions. This scoping review aims to provide an overarching review mapping FoF research by identifying main topics, gaps in the literature and potential opportunities for bridging different strains of research on FoF. Such a comprehensive scoping review will allow the subsequent creation of an interdisciplinary theoretical and empirical framework, which may help push forward policy and practice innovations for people living with FoF.

Methods and analysis

Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews (PRISMA-ScR), seven main databases will be searched from 2000 to the date of the start of the review: Cochrane Database of Systematic Reviews, CINAHL, Embase, MEDLINE, PsycInfo, Scopus and Web of Science. The review will include original research in English, published between 2000 and January 2023. Quality checks will be conducted collegially. Data will be extracted and analysed using PRISMA-ScR charting tools and conventions.

Ethics and dissemination

No ethics approval is required for the review. The results will be submitted to a peer-reviewed journal and presented at academic conferences. The outcomes will be disseminated through social media, opinion pieces and science communication platforms to reach a wider audience.

Registration

The scoping review was registered with the Open Science Framework (https://osf.io/gyzjq).
Effectiveness of virtual reality technology in symptom management of end-of-life patients: protocol of a systematic review and meta-analysis
Authors: Xia Wanting , Chen Yongyi , Liu Xiangyu , Chen Furong , Yan Mengyao , Xu Xianghua
Published: February 2023

Introduction

With the worsening of population ageing globally, the number of the elderly with chronic and incurable diseases such as malignant tumours is gradually increasing, and the need for palliative care is growing. As a primary task in the end-of-life phase, symptom management is an essential aspect of palliative care, which aims to alleviate distressing symptoms of terminally ill patients and improve their quality of life. Virtual reality (VR) technology, which allows the creation of simulated environments in which a three-dimensional experience is generated, has been increasingly used in palliative care for symptom management. Therefore, we aim to conduct a systematic review to investigate the effects of VR-based interventions on end-of-life patients.

Methods and analysis

This protocol for conducting a systematic review and meta-analysis will be prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. We will conduct a series of searches from inception to 31 July 2022 in the following databases: PubMed, Embase, Web of Science, the Cochrane Library, JBI, EBSCO, CNKI, Wanfang and SinoMed. The key concepts of ‘virtual reality’ and ‘end-of-life’ will be combined in each database using both free-text terms and controlled vocabulary terms (eg, MeSH/Emtree terms), if available. Two independent reviewers will use raw data to explore the effectiveness of VR for symptom management in end-of-life patients. The Cochrane Risk-of-Bias tool will be used to assess the risk of bias of included studies. Disagreements will be resolved by a third independent reviewer to reach a consensus. For the included articles, Review Manager software will be used for data synthesis and I2statistics will be used to measure the heterogeneity. Subgroup analyses and sensitivity analyses will be used to identify the source of heterogeneity.

Ethics and dissemination

As this is a protocol for a systematic review and meta-analysis, patients will not be included in this study. For this reason, ethical approval is not required. In order to disseminate the research findings, the results and conclusions of this review will be submitted to a worldwide journal.

PROSPERO registration number

CRD42022344679.
Anxiety and stress among healthcare professionals during COVID-19 in Ethiopia: systematic review and meta-analysis
Authors: Hasen Aragaw Asfaw , Seid Abubeker Alebachew , Mohammed Ahmed Adem
Published: February 2023

Objective

This study intended to assess the impact of COVID-19 pandemic on anxiety and stress among healthcare professionals in Ethiopia.

Design

This study applied a design of systematic review and meta-analysis of observational studies.

Data sources

Eligibility criteria and outcomes

Observational studies examining anxiety and stress among healthcare professionals in Ethiopia following COVID-19 pandemic were considered. The primary outcomes were the prevalence of anxiety and stress and the secondary outcomes were factors associated to the prevalence of anxiety and stress.

Data extraction and synthesis

Two authors extracted the data and performed quality assessment independently. The Newcastle-Ottawa Scale was used to evaluate the quality of eligible studies. Random-effect model with the inverse variance method was used to estimate the pooled effect size of the outcome variables with its 95% CI. Publication bias was checked by DOI plot and Luis Furuya Kanamori index. Stata V.14.0 (StataCorp) software was used for statistical analysis.

Results

Thirteen studies were included. From eight studies the pooled prevalence of anxiety was 46% (95% CI 0.30% to 0.61%, τ2=0.0497, I2=99.07%, p<0.001). Nine studies reported about stress and the pooled prevalence was 51% (95% CI 0.41% to 0.62%, τ2=0.0253, I2=97.85%, p<0.001)). Age, sex, marital status, working department, history of contact with confirmed COVID-19 cases and profession were associated factors for high level of anxiety and stress.

Conclusions

COVID-19 pandemic highly affects mental health of healthcare professionals in Ethiopia. Anxiety and stress were among reported mental health problems among healthcare professionals during the pandemic. Timely psychological counselling programmes should be applied for healthcare professionals to improve the general mental health problems.

PROSPERO registration number

CRD42022314865.
Predictors of mitral valve haemodynamics after mitral valve repair for degenerative mitral regurgitation
Authors: Rumman Rawan K , Verma Subodh , Chan Vincent , Mazer David , Quan Adrian , Hibino Makoto , De Varennes Benoit , Chu Michael W A , Latter David , Teoh Hwee , Yanagawa Bobby , Leong-Poi Howard , Connelly Kim A
Published: February 2023

Objective

Intraoperative predictors of functional mitral valve (MV) stenosis after surgical repair of mitral regurgitation (MR) caused by prolapse remain poorly characterised. This study evaluated the effect of annuloplasty size on postoperative MV haemodynamics during exercise and evaluated predictors of MV hemodynamics.

Methods

104 patients were randomly assigned to leaflet resection or preservation for surgical repair of MR in the Canadian Mitral Research Alliance CardioLink-2 study. In this post hoc analysis, we compared MV haemodynamics between the two surgical groups and examined the relationship between annuloplasty size and MV haemodynamics 1 year after repair in the combined groups. Echocardiograms were performed at baseline and intraoperatively. Exercise transthoracic echocardiography was performed 1 year postoperatively. Multivariable linear regression analysis was used to identify predictors of exercise MV gradients at follow-up.

Results

Mean age of participants was 65±10 years, and 83% were male. Median annuloplasty size was 34 (IQR 32–36). Dividing by the median, 48 (46%) had annuloplasty size of <34 mm and 56 (54%) had ≥34 mm. Mean and peak exercise gradients at 1 year were 11±5 mm Hg and 22±9 mm Hg in <34, and 6±3 mm Hg and 14±5 mm Hg in ≥34 (p<0.001). Rate of residual MR was similar in both groups. In multivariable analyses, annuloplasty size of ≥34 mm was associated with lower mean and peak exercise gradients at 12 months, after adjustment for repair type, age, sex, heart rate and body surface area (β −4.1, 95% CI −6 to –3, p<0.001, and β −7 95% CI −10 to –4, p<0.001, respectively). Intraoperative mean and peak MV gradients by transesophageal echocardiography independently predicted mean and peak resting and exercise gradients at follow-up (p<0.001). Similar results were obtained in both leaflet resection and preservation.

Conclusion

Annuloplasty size of ≥34 mm is associated with a 4 and 7 mm Hg reduction in mean and peak exercise MV gradients, respectively, 1 year post MV repair regardless of the repair strategy used. Intraoperative TEE MV gradients predict exercise MV gradients 1 year post repair.

Trial registration number

NCT02552771.
Socioeconomic position at the age of 30 and the later risk of a mental disorder: a nationwide population-based register study
Authors: Hakulinen Christian , Komulainen Kaisla , Suokas Kimmo , Pirkola Sami , Pulkki-Råback Laura , Lumme Sonja , Elovainio Marko , Böckerman Petri
Published: February 2023

Background

A study was undertaken to examine the association between multiple indicators of socioeconomic position (SEP) at the age of 30 and the subsequent risk of the most common mental disorders.

Methods

All persons born in Finland between 1966 and 1986 who were alive and living in Finland at the end of the year when they turned 30 were included. Educational attainment, employment status and personal total income were used as the alternative measures of SEP. Cox proportional hazards models were used to examine the association of SEP at the age of 30 with later risk of mental disorders. Additional analyses were conducted using a sibling design to account for otherwise unobserved shared family characteristics. Competing risks models were used to estimate absolute risks.

Results

The study population included 1 268 768 persons, 26% of whom were later diagnosed with a mental disorder. Lower SEP at age 30 was consistently associated with a higher risk of being later diagnosed with a mental disorder, even after accounting for shared family characteristics and prior history of a mental disorder. Diagnosis-specific analyses showed that the associations were considerably stronger when substance misuse or schizophrenia spectrum disorders were used as an outcome. Absolute risk analyses showed that, by the age of 52 years, 58% of persons who had low educational attainment at the age of 30 were later diagnosed with a mental disorder.

Conclusions

Poor SEP at the age of 30 is associated with an increased risk of being later diagnosed with a mental disorder.
Targeting Cbl-b in cancer immunotherapy
Authors: Augustin Ryan C. , Bao Riyue , Luke Jason J.
Published: February 2023

Cancer immunotherapy with immune-checkpoint blockade has improved the outcomes of patients with various malignancies, yet a majority do not benefit or develop resistance. To address this unmet need, efforts across the field are targeting additional coinhibitory receptors, costimulatory proteins, and intracellular mediators that could prevent or bypass anti-PD1 resistance mechanisms. The CD28 costimulatory pathway is necessary for antigen-specific T cell activation, though prior CD28 agonists did not translate successfully to clinic due to toxicity. Casitas B lymphoma-b (Cbl-b) is a downstream, master regulator of both CD28 and CTLA-4 signaling. This E3 ubiquitin ligase regulates both innate and adaptive immune cells, ultimately promoting an immunosuppressive tumor microenvironment (TME) in the absence of CD28 costimulation. Recent advances in pharmaceutical screening and computational biology have enabled the development of novel platforms to target this once ‘undruggable’ protein. These platforms include DNA encoded library screening, allosteric drug targeting, small-interfering RNA inhibition, CRISPR genome editing, and adoptive cell therapy. Both genetic knock-out models and Cbl-b inhibitors have been shown to reverse immunosuppression in the TME, stimulate cytotoxic T cell activity, and promote tumor regression, findings augmented with PD1 blockade in experimental models. In translating Cbl-b inhibitors to clinic, we propose specific gene expression profiles that may identify patient populations most likely to benefit. Overall, novel Cbl-b inhibitors provide antigen-specific immune stimulation and are a promising therapeutic tool in the field of immuno-oncology.
Poverty Reduction Strategies–Lessons from the Asian and Pacific Region on Inclusive Development
Authors: Chatterjee Shiladitya
Published: February 2023

The Asian and Pacific region has made remarkable advances in reducing poverty. This paper surveys the main contributions that attempt to explain the causes behind the region’s success in poverty reduction, and assesses the impact of inclusive development policies pursued. Looking broadly at the different experiences of East and Southeast Asia on one hand and South Asia on the other, the paper classifies the explanations provided in the literature for the poverty reduction experience of the region into two groups: those explaining the phenomenal increase in economic growth and its relation to poverty reduction; and those examining the policies that have contributed directly to fostering inclusiveness of the development process.
Foreign Exchange Reserves, Exchange Rate Regimes, and Monetary Policy: Issues in Asia
Authors: Terada-Hagiwara Akiko
Published: February 2023

This paper seeks to outline issues arising from rapid foreign exchange reserve accumulations in Asia. Attention is paid to People’s Republic of China and India for the significance of the accumulation fed by surges in capital inflows. The paper finds that sterilization interventions by the two economies appear to be effective in curbing credit growth, but the impacts appear limited and short-lived. In this regard, adjustments of exchange rate policies are called for to have more freedom in policy options, though incentives to live with exchange rate fluctuations are still limited, and in fact the currencies have been managed more tightly than before. Therefore, the paper argues that, while maintaining the current exchange rate practices with capital controls in place, domestic reforms should be pushed further to be ready for capital account convertibility and more exchange rate flexibility in the long term.
Some New Results on δ(k)-Coloring of Graphs
Authors: Ellumkalayil Merlin Thomas , Samuel Libin Chacko , Naduvath Sudev
Published: February 2023

Let [Formula: see text] be the minimum number of distinct resources or equipment such as channels, transmitters, antennas and surveillance equipment required for a system’s stability. These resources are placed on a system. The system is stable only if the resources of the same type are placed far away from each other or, in other words, they are not adjacent to each other. Let these distinct resources represent different colors assigned on the vertices of a graph [Formula: see text]. Suppose the available resources, denoted by [Formula: see text], are less than [Formula: see text]. In that case, placing [Formula: see text] resources on the vertices of [Formula: see text] will make at least one equipment of the same type adjacent to each other, which thereby make the system unstable. In [Formula: see text]-coloring, the adjacency between the resources of a single resource type is tolerated. The remaining resources are placed on the vertices so that no two resources of the same type are adjacent to each other. In this paper, we discuss some general results on the [Formula: see text]-coloring and the number of bad edges obtained from the same for a graph [Formula: see text]. Also, we determine the minimum number of bad edges obtained from [Formula: see text]-coloring of few derived graph of graphs. The number of bad edges which result from a [Formula: see text]-coloring of [Formula: see text] is denoted by [Formula: see text].
An integrated sequence stratigraphic analysis of the early Marsdenian substage of the Millstone Grit Group, Central Pennines, UK
Authors: Brettle Matthew J. , Waters Colin N. , Davies Sarah J.
Published: February 2023

The early Marsdenian substage (Millstone Grit Group) of the Pennines comprises repeated deltaic cycles separated by ammonoid-bearing marine bands. This cyclicity, controlled by the combined forces of glacio-eustasy and modulations in sediment supply, provides an important outcrop area for the application of sequence stratigraphic principles.

A new correlation framework is presented where two orders of sequence are identified: (1) a low-order sequence, within which marine bands (R
2a
1, R
2b
1, R
2b
2 and R
2b
3) represent a maximum flooding surface, and (2) high-order sequences nested within the low-order sequences. By integrating and correlating key exposures, historic well boreholes and field mapping, lateral changes in facies and facies association are observed, and palaeogeographic trends mapped. This allows the variation in sequence and systems tract stacking patterns to be interpreted. Three orders of Milankovitch cyclicity are inferred to control the sequence stacking patterns; long-duration (
c.
400 ka) eccentricity oscillation controlling maximum flooding events represented by the R
2a
1 and R
2b
2 marine bands, sub-100 ka obliquity oscillations (controlling the R
2b
1, R
2b
2 and R
2b
3 marine bands and intervening low-order sequence boundaries), and precessional frequencies (
c.
25 ka) which may control the periodicity of the high-order sequences.

Supplementary material:
Locality details, including lithostratigraphic units observed, gross and sand thicknesses within sequences, and palaeocurrent data measured are available at
https://doi.org/10.6084/m9.figshare.c.6408203
Testosterone enhances taurine synthesis by upregulating androgen receptor and cysteine sulfinic acid decarboxylase expressions in male mouse liver
Authors: Zhang Di , Fan Jingjing , Liu Hui , Qiu Guobin , Cui Sheng
Published: February 2023

This study demonstrates that testosterone functions to enhance taurine synthesis by interacting with androgen receptor and binding to cysteine sulfinate decarboxylase ( CSAD) promoter zone. Whereas estrogen has no significant effects either on liver CSAD expression or taurine synthesis in male mice and suggests that the effects of sex steroids on taurine synthesis in the liver have gender differences. These new findings are the potential for establishing effective protective and therapeutic strategies for liver diseases.
Single-day and multi-day exposure to orogastric gavages does not affect intestinal barrier function in mice
Authors: Hanning Nikita , Verboven Rosanne , De Man Joris G. , Ceuleers Hannah , De Schepper Heiko U. , Smet Annemieke , De Winter Benedicte Y.
Published: February 2023

Exposure of mice to serial orogastric gavages over the course of 10 days leads to a small but significant increase in plasma corticosterone levels, indicating the presence of a limited amount of stress that is absent after a single-day treatment. This minor stress after multi-day gavages results in increased fecal pellet production and fecal water content in exposed compared with nontreated mice but does not affect the intestinal barrier function in the distal colon, proximal colon, or terminal ileum.
Diet-induced obesity alters intestinal monocyte-derived and tissue-resident macrophages and increases intestinal permeability in female mice independent of tumor necrosis factor
Authors: Breznik Jessica A. , Jury Jennifer , Verdú Elena F. , Sloboda Deborah M. , Bowdish Dawn M. E.
Published: February 2023

We found that diet-induced obesity in female mice has tissue- and time-dependent effects on intestinal paracellular permeability as well as monocyte-derived and tissue-resident macrophage numbers, surface marker phenotype, and intracellular production of the cytokines IL-10 and TNF. These changes were not mediated by TNF.
Sensitization of colonic nociceptors by IL-13 is dependent on JAK and p38 MAPK activity
Authors: Barker Katie H. , Higham James P. , Pattison Luke A. , Chessell Iain P. , Welsh Fraser , Smith Ewan St. J. , Bulmer David C.
Published: February 2023

The pro-inflammatory cytokine interleukin-13 (IL-13) is elevated in gastrointestinal (GI) diseases. This study confirms a role for IL-13 in colonic afferent sensitization and defines a role for downstream Janus kinase (JAK) and p38 MAPK signaling in colonic mechanosensitization. It is shown that IL-13-mediated increase in [Ca2+]i in capsaicin-sensitive sensory neurons is dependent on p38 MAPK, and JAK signaling and IL-13-induced sensitization of colonic afferents to noxious mechanical distension is abolished by inhibition of p38 MAPK and JAK.
Release of extracellular superoxide dismutase into alveolar fluid protects against acute lung injury and inflammation in Staphylococcus aureus pneumonia
Authors: Sul Christina , Lewis Caitlin , Dee Nathan , Burns Nana , Oshima Kaori , Schmidt Eric , Vohwinkel Christine , Nozik Eva
Published: February 2023

Acute respiratory distress syndrome (ARDS) remains a significant cause of morbidity and mortality in critically ill patients. Oxidative stress and inflammation play a crucial role in the pathogenesis of ARDS. Extracellular superoxide dismutase (EC-SOD) is abundant in the lung and is an important enzymatic defense against superoxide. Human single-nucleotide polymorphism in matrix binding region of EC-SOD leads to the substitution of arginine to glycine at position 213 (R213G) and results in release of EC-SOD into alveolar fluid, without affecting enzyme activity. We hypothesized that R213G EC-SOD variant protects against lung injury and inflammation via the blockade of neutrophil recruitment in infectious model of methicillin-resistant S. aureus (MRSA) pneumonia. After inoculation with MRSA, wild-type (WT) mice had impaired integrity of alveolar-capillary barrier and increased levels of IL-1β, IL-6, and TNF-α in the broncho-alveolar lavage fluid (BALF), while infected mice expressing R213G EC-SOD variant maintained the integrity of alveolar-capillary interface and had attenuated levels of proinflammatory cytokines. MRSA-infected mice expressing R213G EC-SOD variant also had attenuated neutrophil numbers in BALF and decreased expression of neutrophil chemoattractant CXCL1 by the alveolar epithelial ATII cells, compared with the infected WT group. The decreased neutrophil numbers in R213G mice were not due to increased rate of apoptosis. Mice expressing R213G variant had a differential effect on neutrophil functionality—the generation of neutrophil extracellular traps (NETs) but not myeloperoxidase (MPO) levels were attenuated in comparison with WT controls. Despite having the same bacterial load in the lung as WT controls, mice expressing R213G EC-SOD variant were protected from extrapulmonary dissemination of bacteria.
Publishing particulars: Part 3. General writing tips, editing, and responding to peer review
Authors: Seals Douglas R.
Published: February 2023

In Part 3 of this Perspective on Publishing Particulars, I begin by providing several general writing tips to consider when developing a manuscript for publication. I then discuss the process involved in rigorously editing research papers and advance some important considerations for manuscript submission. I next share my thoughts and recommendations when attempting to interpret and respond to comments from the manuscript peer review process. Finally, I discuss author responsibilities after a manuscript is accepted for publication. Overall, this portion of the 3-part commentary seeks to complete a broader discussion on publishing in the biomedical sciences aimed at better informing early-stage investigators about many of the nuances of this critical area of professional development.
Suppression of GCH1 Sensitizes Ovarian Cancer and Breast Cancer to PARP Inhibitor
Authors: Wang Siyuan , Xia Yu , Huang Pu , Xu Cheng , Qian Yiyu , Fang Tian , Gao Qinglei
Published: February 2023

Background. Breast and ovarian cancers are common malignancies among women, contributing to a significant disease burden, and are characterized by a high level of genomic instability, owing to the failure of homologous recombination repair (HRR). Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) could elicit the synthetic lethal effect of tumor cells in patients with homologous recombination deficiency, ultimately achieving a favorable clinical benefit. However, primary and acquired resistance remain the greatest hurdle, limiting the efficacy of PARP inhibitors; thus, strategies conferring or augmenting tumor cell sensitivity to PARP inhibitors are urgently required. Methods. Our RNA-seq data of niraparib-treated and -untreated tumor cells were analyzed by R language. Gene Set Enrichment Analysis (GSEA) was applied to assess the biological functions of GTP cyclohydrolase 1 (GCH1). Quantitative real-time PCR, Western blotting, and immunofluorescence were applied to confirm the upregulation of GCH1 upon niraparib treatment at transcriptional and translational levels. Immunohistochemistry of patient-derived xenograft (PDX)-derived tissue sections further validated that niraparib increased GCH1 expression. Tumor cell apoptosis was detected by flow cytometry, while the superiority of the combination strategy was confirmed in the PDX model. Results. The expression of GCH1 was aberrantly enriched in breast and ovarian cancers and increased after niraparib treatment via JAK-STAT signaling. GCH1 was also demonstrated to be associated with the HRR pathway. Subsequently, the enhancement of the tumor-killing effect of PARP inhibitors induced by GCH1 suppression using siRNA and GCH1 inhibitor was validated by flow cytometry in vitro. Finally, using the PDX model, we further demonstrated that GCH1 inhibitors markedly potentiated PARP inhibitors’ antitumor efficacy in vivo. Conclusion. Our results illustrated that PARP inhibitors promote GCH1 expression via the JAK-STAT pathway. We also elucidated the potential relationship between GCH1 and the homologous recombination repair pathway and proposed a combination regimen of GCH1 suppression with PARP inhibitors in breast and ovarian cancers.
Topically Applied Luteolin /Quercetin-Capped Silver Nanoparticle Ointment as Antileishmanial Composite: Acceleration Wound Healing in BALB/c Mice
Authors: Ebrahimzadeh Azadeh , Karamian Mehdi , Abedi Farshid , Hanafi-Bojd Mohammad Yahya , Ghatee Mohammd Amin , Hemmati Mina , Alemzadeh Effat
Published: February 2023

Cutaneous leishmaniasis is a major health problem in several parts of the world. However, existing drugs have various therapeutic effects on different Leishmania species and also cause many side effects. This study focuses on the use of the aqueous extract of quercetin in producing silver nanoparticles for the experimental treatment of cutaneous leishmaniasis in laboratory mice. Silver nanoparticles (AgNPs) were synthesized using quercetin and characterized by UV-Vis spectroscopy, DLS, FTIR, and FESEM. We investigated the antileishmanial activity of green synthesized AgNPs in vitro and in vivo. Synthesized AgNPs from quercetin macromolecules showed promising antileishmanial activity at an IC50 of 125 μg/ml against promastigotes in vitro. In the in vivo study, L. major-infected BALB/c mice were treated topically with luteolin/quercetin-capped silver nanoparticle (AgNPQct) ointment for 21 consecutive days. As a result, this ointment reduced the inflammatory response compared to the untreated group (

p

 < 0.05). The size of lesions in the luteolin/AgNPQct group showed a slight increase compared to other groups (

p

 < 0.01). Biogenic silver nanoparticles along with the luteolin macromolecule can be an effective and reliable candidate for the design of antileishmanial drugs in the future.
Zinc Chloride Can Mitigate the Alterations in Metallothionein and Some Apoptotic Proteins Induced by Cadmium Chloride in Mice Hepatocytes: A Histological and Immunohistochemical Study
Authors: Bayram Enas Nihad , Al-Bakri Nahla A. , Al-Shmgani Hanady S.
Published: February 2023

The heavy metal cadmium is extremely harmful to both humans and animals. Zinc supplementation protects the biological system and reduces cadmium-induced toxicity. This study aimed to determine whether zinc chloride (ZnCl2) could protect male mice with the damaged liver induced by cadmium chloride (CdCl2). The protective role of zinc chloride and expression of the metallothionein (MT), Ki-67, and Bcl-2 apoptotic proteins in hepatocytes were studied after subchronic exposure of mice to cadmium chloride for 21 days. Thirty male mice were randomly categorized into 6 groups (5 mice/group) as follows: a control group that did not receive any treatment, a group given ZnCl2 at 10 mg/kg alone, and two groups received ZnCl2 (10 mg/kg) in combination with CdCl2 at two concentrations (1.5 and 3 mg/kg), while the last two groups received CdCl2 alone at 1.5 and 3 mg/kg, respectively. Immunohistochemical examination revealed a decrease in Ki-67 expression in Kupffer and endothelial cells, which reflected cell proliferation downregulation accompanied by MT increased expression. However, the Bcl-2 was ameliorated and reduced to demonstrate an enhanced rate of necrosis rather than apoptosis. Furthermore, histopathological results showed significant alteration such as hepatocytes with a pyknotic nucleus, infiltration of inflammatory cells around the central vein, and the presence of many binucleated hepatocytes. Zinc chloride treatment resulted in histological and morphological improvements that were average in the expression of apoptosis proteins modifications induced by cadmium. Our findings revealed that the positive effects of zinc might be linked to the high metallothionein expression and enhanced cell proliferation. Furthermore, at low-dose exposure, cadmium-induced damage to cells could be more closely related to necrosis rather than apoptosis.
The Dynamic Model and Control Algorithm for the Active Suspension System
Authors: Nguyen Duc Ngoc , Nguyen Tuan Anh
Published: February 2023

Road surface roughness is the leading cause of vehicle oscillation. The suspension system is used to dampen these oscillations. The active suspension system equipped with a hydraulic actuator is more efficient than the passive one. Therefore, it is used to replace the passive suspension system. The article reviews and analyses models and control algorithms for active suspension systems. In this article, the author mentioned three dynamic models commonly used to simulate vehicle oscillations: a quarter‐dynamic model, a half‐dynamic model, and a fully dynamic model. Each hydraulic actuator can be considered a state variable in the dynamic model. Besides, the control algorithm for the suspension system is significant. Algorithms like PID (proportional–integral–derivative) and LQR (linear quadratic regulator) will fit the linear model. In contrast, the nonlinear model’s algorithms, such as SMC (sliding mode control), fuzzy, and ANN (artificial neural network), will perform better. Overall, vehicle oscillation can be significantly improved once an active suspension system is used. The contents analysed in this article will be the database for selecting control models and algorithms by other researchers in the future.
Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis Based on GC‐MS, Network Pharmacology, and Molecular Docking
Authors: Li Shengmao , Huang Yu , Liu Lin , Zhang Fan , Ao Hui , Luo Yingping
Published: February 2023

Objective. Magnoliae officinalis cortex (MOC) is one of the most frequently used traditional Chinese medicine (TCM) for the treatment of acute pancreatitis (AP). Magnolia volatile oil (MVO) is considered to be one of the main active ingredients in MOC for AP treatment. However, the underlying mechanism of MVO in AP therapy is unknown. Methods. An integrated strategy of gas chromatography‐mass spectrum (GC‐MS), network pharmacology, and molecular docking simulation was employed to predict underlying mechanism of MVO in AP treatment. First, the compounds of MVO were identified by GC‐MS, and the targets of the identified characteristic compounds were collected from several databases, as well as AP‐related targets. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to obtain the mechanism. Moreover, the binding activity between core therapeutic targets and their corresponding compounds was evaluated by molecular docking simulation. Results. GC‐MS results showed a total of 35 compounds that appeared in at least 18 out of 20 chromatograms were considered as characteristic compounds of MVO, and 33 compounds of those were identified. Network analysis demonstrated that 33 compounds regulated 142 AP‐related targets. Of those, 8 compounds (α‐eudesmol, γ‐eudesmol, (−)‐terpinen‐4‐ol, terpineol, hinesol, linalool, borneol, and β‐eudesmol) and 8 targets (TNF, IL‐1β, PPARγ, PPARα, PTGS2, NCOA1, CNR1, and ESR1) have a close relationship with AP treatment and were recognized as the key active compounds and the core therapeutic targets, respectively. The 142 targets were involved in both inflammation and calcium overload‐related biological pathways, such as neuroactive ligand‐receptor interaction, estrogen, MAPK, and calcium signaling pathway. Moreover, molecular docking simulation indicated that the 8 core therapeutic targets strongly interacted with their corresponding compounds. Conclusions. In summary, the present study elucidated that the efficacy of MVO in AP treatment might be attributed to anti‐inflammation and inhibition of calcium overload through multicomponents and multitargets.
Service Users’ Perspectives of a National Social Prescribing Programme to Address Loneliness and Social Isolation: A Qualitative Study
Authors: Thompson Jill , Holding Eleanor , Haywood Annette , Foster Alexis
Published: February 2023

Loneliness is considered to be a global public health challenge, impacting a range of physical and mental health conditions. Social prescribing, whereby service users are signposted into community-based activities and social groups by a community link worker, has been suggested as one mechanism to reduce service users’ loneliness and social isolation. This paper reflects on service users’ experiences of accessing a national social prescribing scheme. Drawing on qualitative findings from interviews with service users who were receiving support through a social prescribing programme between October 2017 and December 2018 (n = 26, with n = 12 interviewed a second time), we reflect on their experiences of the programme. We consider some of the complexities of providing short-term support with a focus on signposting people into local activities, when many service users prefer the companionship of their link worker. Furthermore, we highlight some of the difficulties in ending short-term support. Crucially, we highlight the importance of considering the intersection of the social determinants of health. We suggest that social prescribing schemes may exacerbate inequalities if consideration is not given to the ways in which people are (dis)advantaged in accessing the social capital necessary for their initial and continued involvement.
Development and Validation of the Need for Online Social Feedback (NfOSF) Scale
Authors: Duradoni Mirko , Spadoni Veronica , Gursesli Mustafa Can , Guazzini Andrea
Published: February 2023

People are known to adjust their behavior based on social information. Starting from 2004, social media rapidly became a new social arena for human interaction, and scholars widely studied the effect of likes on people’s psyche and behavior. However, likes are just one of the possible social feedbacks among many others on social media. Moreover, social feedback influence should be analyzed recognizing individual differences in people’s needs and desires for them. This work was aimed at developing and validating (internally and externally) a scale able to capture people’s perceived need for online social feedback (NfOSF) applicable to most social media platforms. Data coming from 1403 Italian participants were used for this purpose. Exploratory and confirmatory factor analyses appeared to support a two-factor structure for the NfOSF scale, while Pearson’s correlation confirmed the expected positive relations of NfOSF factors with Narcissism, Need to Belong, FOMO, and Social media reputation perception. Eventually, NfOSF scale reliability appeared optimal.
Selecting Online Channel Mode for Green Products in a Capital‐Constrained Platform Supply Chain
Authors: Zhang Guobao , Cheng Xinhui , Zhang Zhichao , Zheng Yanyan
Published: February 2023

This paper investigates operational decisions and online channel mode selection for green products with an e‐commerce supply chain in which the manufacturer is subject to capital constraint. Starting from a Stackelberg game framework where the platform acts as a leader, two different online channel modes applied with an e‐commerce supply chain are explored for equilibria, respectively. This paper then extends to a different supply chain with a reversed channel leadership, so as to reveal how the supply chain leaderships affect the equilibriums and supply chain performance. With the analytical studies, several important and interesting insights are derived. For example, but not limited to, the following is found: (a) the equilibrium decisions of the capital‐constrained supply chain highly rely on the associated interest rate but are independent of the initial capital level of the financially‐constrained manufacturer; (b) the platform and the capital‐constrained manufacturer act largely differently when choosing the optimal online channel mode for themselves; (c) a win‐win situation benefiting two parties holds when and only when the two members choose the agency mode under certain conditions; (d) the impacts of the supply chain leaderships and online channel modes on the consumer surplus and social welfare are clearly revealed. These results derived in our paper shed lights on industrial practicer on how to effectively make such decision‐making in platform economy. The members in an e‐commerce supply chain can appropriately determine their decisions such as commission and slotting fee to reach a win‐win situation for two parties.
Compositing Nanostructured Polyaniline with Single-Walled Carbon Nanotubes for High Thermoelectric Performance
Authors: Luo Qunyi , Wu Xin , Wang Erqiang , Guo Cun-Yue
Published: February 2023

In the face of the growing energy crisis and demand on environmental protection, organic thermoelectric (TE) materials have been coming under the spotlight from global researchers as a potential countermeasure. However, there have been few studies on the relationship between the morphology of conductive polymers (CPs) and their TE performance. In this work, nanostructured polyaniline (PANI) was synthesized by interfacial polymerization with the addition of organic solvents of different polarities, including cyclohexane (CYH), carbon tetrachloride (CCl4), toluene (MB), dichloromethane (DCM), and dimethyl sulfoxide (DMSO). Physical mixing PANI with single-walled carbon nanotubes (SWCNTs) affords PANI/SWCNT composites. The composite of PANI nanobelts and 10 wt% SWCNTs achieves a power factor (PF) of 5.13 ± 0.56 μW m-1 K-2 at room temperature (RT). Spherical PANI doped with 50 wt% SWCNTs followed by pressing affords maximal room temperature PF value of

178.10
±
3.77

 μW m-1 K-2. A prototype TE generator (TEG) constructed with seven pairs of legs of as-prepared PANI/SWCNT composites and their n-type counterparts generates voltage of

10.27
±
0.15

 mV and output power of

36.65
±
1.18

 nW at temperature difference of about 50°C. This work illustrates that well-regulated PANI nanostructure could significantly affect the TE properties of PANI/SWCNT composites, which are promising in future preparation of high-performance polymer-based composites regarding the fabrication of TE devices suitable for harnessing low-grade waste heat.