bluuebunny/crossref_metadata_2025 huggingface dataset:
Educating the Sickle Cell Team about the Social Work Role
Authors: Moorman Spencer , Johnson Shirley , Raj Ashok B.
Published: December 2023

Background

Sickle cell disease, an often-painful lifelong inherited condition, is layered with acknowledged social determinants of health and systemic social inequities (Hassell, 2010). Psychological stress, depression, and anxiety can be linked with the disease's wrath along with financial hardship, limited healthcare access, racial discrimination, and cognitive and behavioral challenges. Although the need for quality psychosocial support exists for this vulnerable patient population, lack of understanding of the social work role was identified as a barrier to care, along with others, by National Alliance of Sickle Cell Centers (NASCC) social workers at the 2022 consortium conference. Like other disease realms (Bartlett et al., 2022) that have referenced physician lack of knowledge around the breadth of roles, capabilities, training and expertise, the social work scope of practice knowledge gap amongst providers was voiced as a clear barrier to efficient and effective patient care in the sickle cell realm as well. As a result, a subcommittee of NASCC social workers set out to provide an educational guide and breakdown of the social work profession, to help address this ever-present issue.

Methods

Five social workers gathered data of the various social work roles from other NASCC social work participants and online sources. Job descriptions from seven institutions were shared for the project and an itemized breakdown of education level, practicum training and experience, and licensure requirements were outlined.

Results

A detailed table of all tasks, course work, training, licensure, and scope of practice was created and displayed in a presentation for all NASCC in person providers. For each education tier (BSW, MSW, PhD), details of the associated requirements (training hours and course requirements), licensure (CSW, LCSW, LMSW, LBSW, etc.), focus (macro, mezzo, micro) and scope of practice (tasks involved) were displayed via both a table and visual illustration for other disciplines reference and awareness. NASCC medical providers shared their appreciation for the detailed breakdown of social work levels and expressed the need for this guide to educate other interdisciplinary team members and administrative staff alike.

Discussion

Many medical providers are unaware that the term social worker encapsulates varied levels of education, training, licensure, and scopes of practice. It is important for interdisciplinary team members to understand the integral social work role, its capabilities, breadth of skills, and specific responsibilities. Whether a case manager, transition coordinator, or licensed therapist or counselor, knowing the nuances and qualifications of each position under the social work umbrella can help to better inform care processes, referrals, and appropriate access to quality care.
Metabolite itaconate in host immunoregulation and defense
Authors: Yang Wenchang , Wang Yaxin , Tao Kaixiong , Li Ruidong
Published: December 2023

Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (IRG1). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3–IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field.
Functional and kinetics of two efficient phenylalanine ammonia lyase from Pyrus bretschneideri
Authors: Li Guohui , Song Cheng , Manzoor Muhammad Aamir , Li Daoyuan , Cao Yunpeng , Cai Yongping
Published: December 2023

Background

The enzyme phenylalanine ammonia lyase (PAL) controls the transition from primary to secondary metabolism by converting L-phenylalanine (L-Phe) to cinnamic acid. However, the function of PAL in pear plants (Pyrus bretschneideri) has not yet been fully elucidated.

Results

We identified three PAL genes (PbPAL1, PbPAL2 and PbPAL3) from the pear genome by exploring pear genome databases. The evolutionary tree revealed that three PbPALs were classified into one group. We expressed PbPAL1 and PbPAL2 recombinant proteins, and the purified PbPAL1 and PbPAL2 proteins showed strict substrate specificity for L-Phe, no activity toward L-Tyr in vitro, and modest changes in kinetics and enzyme characteristics. Furthermore, overexpression of PbAL1 and PbPAL1-RNAi, respectively, and resulted in significant changes in stone cell and lignin contents in pear fruits. The results of yeast one-hybrid (Y1H) assays that PbWLIM1 could bind to the conserved PAL box in the PbPAL promoter and regulate the transcription level of PbPAL2.

Conclusions

Our findings not only showed PbPAL’s potential role in lignin biosynthesis but also laid the foundation for future studies on the regulation of lignin synthesis and stone cell development in pear fruit utilizing molecular biology approaches.
Epley manoeuvre’s efficacy for benign paroxysmal positional vertigo (BPPV) in primary-care and subspecialty settings: a systematic review and meta-analysis
Authors: Saishoji Yusuke , Yamamoto Norio , Fujiwara Takashi , Mori Hideki , Taito Shunsuke
Published: December 2023

Background

Although previous studies have reported general inexperience with the Epley manoeuvre (EM) among general physicians, no report has evaluated the effect of EM on benign paroxysmal positional vertigo (BPPV) in primary care by using point estimates or certainty of evidence. We conducted this systematic review and meta-analysis and clarified the efficacy of EM for BPPV, regardless of primary-care and subspecialty settings.

Methods

Systematic review and meta-analysis of randomised sham-controlled trials of EM for the treatment of posterior canal BPPV in primary-care and subspecialty settings. A primary-care setting was defined as a practice setting by general practitioners, primary-care doctors, or family doctors. A systematic search was conducted in January 2022 across databases, including Cochrane Central Resister of Controlled Trial, MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Primary outcomes were the disappearance of subjective symptoms (vertigo), negative findings (Dix–Hallpike test), and all adverse events. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.

Results

Twenty-seven randomised controlled trials were identified. In primary-care settings, EM reduced the subjective symptoms [risk ratio (RR), 3.14; 95% confidence interval (CI), 1.96–5.02]; however, there was no applicable article for all adverse events. In the subspeciality setting, EM reduced the subjective symptoms (RR, 2.42; 95% CI, 1.64–3.56), resulting in an increase in negative findings (RR, 1.81; 95% CI, 1.40–2.34). The evidence exhibited uncertainty about the effect of EM on negative findings in primary-care settings and all adverse events in subspecialty settings.

Conclusions

Regardless of primary-care and subspecialty settings, EM for BPPV was effective. This study has shown the significance of performing EM for BPPV in primary-care settings. EM for BPPV in a primary-care setting may aid in preventing referrals to higher tertiary care facilities and hospitalisation for follow-up.

Trial registration

The study was registered in protocols.io (PROTOCOL INTEGER ID: 51,464) on July 11, 2021.
Creating a supportive environment for older adults in China ——exploring factors associated with the need for home modifications based on a cross-sectional survey in Central China
Authors: Li Jiajing , Wu Bei , Wang Jing
Published: December 2023

Background

A supportive home environment is critical to the safety and quality of life of older adults. Home modification is an effective way to build a supportive home environment for older adults’ aging in place. However, there is a lack of knowledge on older adults’ need for home modifications in China.

Methods

We conducted a cross-sectional survey in three provinces of China (Hubei, Hunan, and Henan) using stratified and cluster sampling methods in 2021. A total of 5485 older adults aged 60 and over were included. The outcome variables were: need for home modifications, level of need, and type of modification needed. Exposure variables included: demographic and socioeconomic characteristics, as well as health conditions. Logistic and Poisson regressions were applied to examine the needs for home modifications and its associated factors.

Results

Nearly 30% of the older adults needed home modifications. The most common choice of home modification was the need for handrails at the bedside, toilet, or threshold (31.64%), and paving un-slip tiles or vinyl flooring (17.45%). Age (IRR = 1.01, P < 0.001), education (IRR = 1.11, P < 0.01), and level of assistance (IRR = 2.31, P < 0.001) were more likely to be positively associated with needs for modification. Participants in the age group of 70 to 79 years, with primary school education, and low-level physically dependent had significantly higher needs for modifications than those of advanced age, lower level of education, or higher level of physically dependent (p < 0.01).

Conclusions

The overall need for home modifications in China is low. Home modification programs are needed to tailor individuals’ needs and provide services to those with the most home modification need.
Pooled prevalence of lymphopenia in all-cause hospitalisations and association with infection: a systematic review and meta-analysis
Authors: Elçioğlu ZC , Errington L , Metes B , Sendama W , Powell J , Simpson AJ , Rostron AJ , Hellyer TP
Published: December 2023

Background

Lymphopenia is defined as a decrease below normal value (often 1.0 x 109 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is associated with an increased risk of hospitalisation secondary to infection, independent of traditional clinical risk factors. In hospital, lymphopenia is associated with increased risk of healthcare-associated infection and mortality. By summarising lymphopenia’s prevalence and impact on clinical outcomes, we can identify an at-risk population and inform future studies of immune dysfunction following severe illness.

Methods

Peer-reviewed search strategy was performed on three databases. Primary objective was to summarise the pooled prevalence of lymphopenia. Primary outcome was infection including pre-existing lymphopenia as a risk factor for admission with infection and as an in-hospital risk factor for healthcare-associated infection. Secondary outcomes were length of stay and mortality. Mortality data extracted included in-hospital, 28/30-day (‘early’), and 90-day/1-year (‘late’) mortality. Meta-analysis was carried out using random-effects models for each outcome measure. Heterogeneity was assessed using I2 statistic. Joanna Briggs Institute checklist for cohort studies was used to assess risk of bias. The protocol was published on PROSPERO.

Results

Fifteen observational studies were included. The pooled prevalence of lymphopenia in all-cause hospitalisations was 38% (CI 0.34-0.42, I2= 97%, p< 0.01). Lymphopenia was not associated with an infection diagnosis at hospital admission and healthcare associated infection (RR 1.03; 95% CI 0.26-3.99, p=0.97, I2 = 55% and RR 1.31; 95% CI 0.78-2.20, p=0.31, I2=97%, respectively), but was associated with septic shock (RR 2.72; 95% CI 1.02-7.21, p=0.04, I2 =98%). Lymphopenia was associated with higher in-hospital mortality and higher ‘early’ mortality rates (RR 2.44; 95% CI 1.71-3.47, p < 0.00001, I2 = 89% and RR 2.05; 95% CI 1.64-2.56, p < 0.00001, I2 = 29%, respectively). Lymphopenia was associated with higher ‘late’ mortality (RR 1.59; 1.33-1.90, p < 0.00001, I2 = 0%).

Conclusions

This meta-analysis demonstrates the high prevalence of lymphopenia across all-cause hospitalisations and associated increased risk of septic shock, early and late mortality. Lymphopenia is a readily available marker that may identify immune dysfunctional patients. Greater understanding of immune trajectories following survival may provide insights into longer-term poor clinical outcomes.
How is the COVID-19 pandemic impacting our life, mental health, and well-being? Design and preliminary findings of the pan-Canadian longitudinal COHESION study
Authors: Gabet Stephan , Thierry Benoit , Wasfi Rania , Simonelli Guido , Hudon Catherine , Lessard Lily , Dubé Ève , Nasri Bouchra , Kestens Yan , Moullec Grégory
Published: December 2023

Background

With the advent of the COVID-19 pandemic, in-person social interactions and opportunities for accessing resources that sustain health and well-being have drastically reduced. We therefore designed the pan-Canadian prospective COVID-19: HEalth and Social Inequities across Neighbourhoods (COHESION) cohort to provide a deeper understanding of how the COVID-19 pandemic context affects mental health and well-being, key determinants of health, and health inequities.

Methods

This paper presents the design of the two-phase COHESION Study, and descriptive results from the first phase conducted between May 2020 and September 2021. During that period, the COHESION research platform collected monthly data linked to COVID-19 such as infection and vaccination status, perceptions and attitudes regarding pandemic-related measures, and information on participants’ physical and mental health, well-being, sleep, loneliness, resilience, substances use, living conditions, social interactions, activities, and mobility.

Results

The 1,268 people enrolled in the Phase 1 COHESION Study are for the most part from Ontario (47%) and Quebec (33%), aged 48 ± 16 years [mean ± standard deviation (SD)], and mainly women (78%), White (85%), with a university degree (63%), and living in large urban centers (70%). According to the 298 ± 68 (mean ± SD) prospective questionnaires completed each month on average, the first year of follow-up reveals significant temporal variations in standardized indexes of well-being, loneliness, anxiety, depression, and psychological distress.

Conclusions

The COHESION Study will allow identifying trajectories of mental health and well-being while investigating their determinants and how these may vary by subgroup, over time, and across different provinces in Canada, in varying context including the pandemic recovery period. Our findings will contribute valuable insights to the urban health field and inform future public health interventions.
Serum lipoprotein(a) and reclassification of coronary heart disease risk; application of prediction in a cross-sectional analysis of an ongoing Iranian cohort
Authors: Ghavami Mojgan , Abdshah Alireza , Esteghamati Sadaf , Hafezi-Nejad Nima , Nakhjavani Manouchehr , Esteghamati Alireza
Published: December 2023

Introduction

Recent studies have introduced elevated lipoprotein(a) (Lp(a)) as a risk factor for coronary heart disease (CHD). This study investigated whether the addition of Lp(a) as a novel biomarker to the Framingham Risk Score (FRS) model improves CHD risk prediction.

Methods

The study included 1101 Iranian subjects (443 non-diabetic and 658 diabetic patients) who were followed for 10 years (2003–2013). Lp(a) levels and CHD events were recorded for each participant.

Results

The Net Reclassification Index (NRI) after adding Lp(a) to the FRS model was 19.57% and the discrimination slope was improved (0.160 vs. 0.173). The Akaike Information Criterion (AIC), a measure of model complexity, decreased significantly after adding Lp(a) to the FRS model (691.9 vs. 685.4, P value: 0.007).

Conclusions

The study concluded that adding Lp(a) to the FRS model improves CHD risk prediction in an Iranian population without making the model too complex. This could help clinicians to better identify individuals who are at risk of developing CHD and to implement appropriate preventive measures.
Women’s autonomy in healthcare decision making: a systematic review
Authors: Idris Idayu Badilla , Hamis Amy Azira , Bukhori Ayuzeity Bistari Md , Hoong David Chan Chee , Yusop Hakimah , Shaharuddin Muhammad Al-Amin , Fauzi Nazmeen Adline Fawwazah A. , Kandayah Thinakaran
Published: December 2023

Objectives

Although there are calls for women’s empowerment and gender equity globally, there are still large disparities regarding women’s autonomy in healthcare decision making. The autonomy of women is believed to be crucial in improving their health-related outcomes. This review discusses factors that influence autonomy among women in healthcare decision making.

Design

Systematic review.

Data sources

PubMed, Web of Science and Scopus were searched from 2017–2022.

Eligibility criteria

The inclusion criteria include original articles, case studies and reports that has been written in the English Language, while manuscripts with no full article, reviews, newspaper reports, grey literatures, and articles that did not answer the review objectives were excluded.

Data extraction and synthesis

We carried out data extraction using a standardized data extraction form, that has been organized using Microsoft Excel. A narrative synthesis was carried out to combine the findings of all included articles.

Results

A total of 70 records were identified and 18 were reviewed, yielding eight articles to be included in the accepted list of studies. All studies were conducted in developing countries and most of the studies were cross sectional. Factors that were associated with women’s autonomy in healthcare decision making were age, women’s education and occupation, husbands’/partners’ education and occupation, residential location or region of residence, household wealth index as well as culture and religion.

Conclusions

Identification of these factors may help stakeholders in improving women’s autonomy in healthcare decision making. Policymakers play a crucial role in healthcare decision making by enacting laws and policies that protect women's rights, promoting gender-sensitive healthcare services, ensuring access to comprehensive information, promoting health education, and supporting vulnerable populations. These efforts ensure women's autonomy including able to access to unbiased and effective healthcare services.
How to adopt technologies in home care: a mixed methods study on user experiences and change of home care in Finland
Authors: Anttila Minna , Koivisto Juha , Luoma Minna-Liisa , Anttila Heidi
Published: December 2023

Background

There is a need for better adoption of technology to meet the needs of home care professionals, older people, and informal caregivers.

Methods

Mixed methods were used to describe and analyse quantitative and qualitative data in a Finnish governmental programme called KATI. The study was three-fold: it 1) listed what kinds of technologies were piloted and deployed in a national study, 2) provided information from the perspectives of home care professionals about requirements to use technology by using focus-group interviews, and 3) assessed experiences of how the adoption of technology changes work and work processes over time by using repeated surveys. Informants in interviews (n = 25) and surveys (n = 90) were home care professionals, who also described the perspectives of older people and informal caregivers. The conceptual models framing the study were adapted from the Technology Acceptance Model and DirVA PROVE-IT.

Results

There were 80 technology pilots, in which variety of technologies were followed in home care. Familiarity with, commitment to and understanding of technology benefits were considered to be requirements for the technology to be used. The adoption of technology provided new skills and information about older people’s wellbeing, realisation of treatment and new possibilities in home care. It developed new procedures to focus on older people’s needs and motivated professionals by gained concrete aid. It enabled them to leave out some concrete procedures as unnecessary. On the other hand, there were also pessimistic and negative experiences when technology use provided nothing new or did not change anything.

Conclusions

The adoption of technology is dependent on the technology and its integration into the prevailing service practice. When they both work, it is possible to leave out unnecessary procedures in care, allocate resources and save time. It is possible to be aware of older people’s safety and how they cope at home, find new ways to get involved in older people’s lives, gain insight, and make changes at work. Continuous on-site training, modifications in service practices and communication throughout organisations is needed.
Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis
Authors: Hu Pan , Lin Letao , Huang Tao , Li Zhenyu , Xiao Meigui , Guo Huanqing , Chen Guanyu , Liu Dengyao , Ke Miaola , Shan Hongbo , Zhang Fujun , Zhang Yanling
Published: December 2023

Background

Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)—derived from exons 2–6 of EYA3–facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions.

Methods

CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model.

Results

CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells.

Conclusions

Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.
Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects
Authors: Wu Xiangyu , Li Tianhang , Jiang Rui , Yang Xin , Guo Hongqian , Yang Rong
Published: December 2023

The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer.
Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing
Authors: Zhang Jinze , Wang He , Tian Yu , Li Tianfeng , Zhang Wei , Ma Li , Chen Xiangjuan , Wei Yushan
Published: December 2023

Gastric cancer (GC) is a pressing global clinical issue, with few treatment options and a poor prognosis. The onset and spread of stomach cancer are significantly influenced by changes in lipid metabolism-related pathways. This study aimed to discover a predictive signature for GC using lipid metabolism-related genes (LMRGs) and examine its correlation with the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients with GC were collected from the TCGA and GEO databases. Data from GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentially expressed LMRGs (DE-LMRGs), differential expression and prognosis studies were carried out. We built a predictive signature using LASSO regression and tested it on the TCGA and GSE84437 datasets. In addition, the correlation of the prognostic signature with the TIME was comprehensively analyzed. In this study, we identified 258 DE-LMRGs in GC and further screened seven survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed genes (DEGs) between the three branches. Two critical genes (GPX3 and NNMT) were identified using the above two gene groups. In addition, a predictive risk score that relies on GPX3 and NNMT was developed. Survival studies in both the TCGA and GEO datasets revealed that patients categorized to be at low danger had a significantly greater prognosis than those identified to be at high danger. Additionally, by employing calibration plots based on TCGA data, the study demonstrated the substantial predictive capacity of a prognostic nomogram, which incorporated a risk score along with various clinical factors. Within the high-risk group, there was a noticeable abundance of active natural killer (NK) cells, quiescent monocytes, macrophages, mast cells, and activated CD4 + T cells. In summary, a two-gene signature and a predictive nomogram have been developed, offering accurate prognostic predictions for general survival in GC patients. These findings have the potential to assist healthcare professionals in making informed medical decisions and providing personalized treatment approaches.
Ropivacaine-loaded hydrogels for prolonged relief of chemotherapy-induced peripheral neuropathic pain and potentiated chemotherapy
Authors: Qing Xin , Dou Renbin , Wang Peng , Zhou Mengni , Cao Chenchen , Zhang Huiwen , Qiu Gaolin , Yang Zhilai , Zhang Jiqian , Liu Hu , Zhu Shasha , Liu Xuesheng
Published: December 2023

Chemotherapy can cause severe pain for patients, but there are currently no satisfactory methods of pain relief. Enhancing the efficacy of chemotherapy to reduce the side effects of high-dose chemotherapeutic drugs remains a major challenge. Moreover, the treatment of chemotherapy-induced peripheral neuropathic pain (CIPNP) is separate from chemotherapy in the clinical setting, causing inconvenience to cancer patients. In view of the many obstacles mentioned above, we developed a strategy to incorporate local anesthetic (LA) into a cisplatin-loaded PF127 hydrogel for painless potentiated chemotherapy. We found that multiple administrations of cisplatin-loaded PF127 hydrogels (PFC) evoked severe CIPNP, which correlated with increased pERK-positive neurons in the dorsal root ganglion (DRG). However, incorporating ropivacaine into the PFC relieved PFC-induced CIPNP for more than ten hours and decreased the number of pERK-positive neurons in the DRG. Moreover, incorporating ropivacaine into the PFC for chemotherapy is found to upregulate major histocompatibility complex class I (MHC-I) expression in tumor cells and promote the infiltration of cytotoxic T lymphocytes (CD8+ T cells) in tumors, thereby potentiating chemotherapy efficacy. This study proposes that LA can be used as an immunemodulator to enhance the effectiveness of chemotherapy, providing new ideas for painless cancer treatment.
Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder
Authors: Greenwald Mark K. , Wiest Katharina L. , Haight Barbara R. , Laffont Celine M. , Zhao Yue
Published: December 2023

Background

BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids.

Methods

This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant’s percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan–Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration–time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately.

Results

BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure–response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events.

Conclusions

These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention.

Trial registration: ClinicalTrials.gov, NCT02357901.
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Authors: Young Juan Joseph , Park Hong-Jai , Kim Minhyung , Par-Young Jennefer , Bartlett Hugh , Kim Hye Sun , Unlu Serhan , Osmani Lais , Shin Min Sun , Bucala Richard , van Dyck Christopher H. , Allore Heather , Mecca Adam P. , You Sungyong , Kang Insoo
Published: December 2023

Background

Memory CD8+ T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8+ T cells expressing low levels of IL-7 receptor alpha (IL-7Rαlow) and the presence of its gene signature (i.e., IL-7Rαlow aging genes) in peripheral blood of older adults without Alzheimer’s disease (AD). Considering age as the strongest risk factor for AD and the recent finding of EM CD8+ T cell expansion, mostly IL-7Rαlow cells, in AD, we investigated whether subjects with AD have alterations in IL-7Rαlow aging gene signature, especially in relation to genes possibly associated with AD and disease severity.

Results

We identified a set of 29 candidate genes (i.e., putative AD genes) which could be differentially expressed in peripheral blood of patients with AD through the systematic search of publicly available datasets. Of the 29 putative AD genes, 9 genes (31%) were IL-7Rαlow aging genes (P < 0.001), suggesting the possible implication of IL-7Rαlow aging genes in AD. These findings were validated by RT-qPCR analysis of 40 genes, including 29 putative AD genes, additional 9 top IL-7R⍺low aging but not the putative AD genes, and 2 inflammatory control genes in peripheral blood of cognitively normal persons (CN, 38 subjects) and patients with AD (40 mild cognitive impairment and 43 dementia subjects). The RT-qPCR results showed 8 differentially expressed genes between AD and CN groups; five (62.5%) of which were top IL-7Rαlow aging genes (FGFBP2, GZMH, NUAK1, PRSS23, TGFBR3) not previously reported to be altered in AD. Unbiased clustering analysis revealed 3 clusters of dementia patients with distinct expression levels of the 40 analyzed genes, including IL-7Rαlow aging genes, which were associated with neurocognitive function as determined by MoCA, CDRsob and neuropsychological testing.

Conclusions

We report differential expression of “normal” aging genes associated with IL‐7Rαlow EM CD8+ T cells in peripheral blood of patients with AD, and the significance of such gene expression in clustering subjects with dementia due to AD into groups with different levels of cognitive functioning. These results provide a platform for studies investigating the possible implications of age-related immune changes, including those associated with CD8+ T cells, in AD.
Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial
Authors: Wang Zhong-yu , Chen Fang-fang , Li Jiang-Tao , Zhao Bai-xiao , Han Li
Published: December 2023

Background

Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA.

Materials and methods

In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial.

Conclusion

The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future.

Trial registration: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.
The role of Traditional Chinese medicine in anti-HBV: background, progress, and challenges
Authors: Ge Feilin , Yang Yan , Bai Zhaofang , Si Lanlan , Wang Xuemei , Yu Jia , Xiao Xiaohe , Liu Yan , Ren Zhigang
Published: December 2023

Chronic hepatitis B (CHB) remains a major world's most serious public health issues. Despite the remarkable effect of nucleos(t)ide analogues (NAs) in inhibiting hepatitis B virus (HBV) deoxyribonucleic acid (DNA) as the first-line drug, there are several limitations still, such as poor antigen inhibition, drug resistance, low-level viremia, restricting patients' functional cure. Due to the constraints of NAs, traditional medicines, such as traditional Chinese medicine (TCM), have become more prevalently used and researched in the clinical treatment of CHB as complementary alternative therapies. As a consequence, the review focuses on the background based on HBV’s life cycle as well as the NAs’ limitations, progress based on direct and indirect pathway of targeting HBV of TCM, and challenges of TCM. We found TCMs play an increasingly important role in anti-HBV. In a direct antiviral way, they regulate HBV infection, replication, assembly, and other aspects of the HBV life cycle. As for indirect way, TCMs can exert anti-HBV effects through targeting the host, including immune regulation, apoptosis, autophagy, oxidative stress, etc. Especially, TCMs have the advantages of strong antigenic inhibition compared to NAs. Specifically, we can combine the benefits of TCMs in strong HBV antigen inhibition with the benefits of NAs in targeted antiviral effects, in order to find a suitable combination of "TCM + NAs" to contribute to Chinese knowledge of the realisation of the “global elimination of HBV by 2030” goal of the World Health Organization.
Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial
Authors: Wasserstein Melissa P. , Lachmann Robin , Hollak Carla , Barbato Antonio , Gallagher Renata C. , Giugliani Roberto , Guelbert Norberto Bernardo , Hennermann Julia B. , Ikezoe Takayuki , Lidove Olivier , Mabe Paulina , Mengel Eugen , Scarpa Maurizio , Senates Ebubekir , Tchan Michel , Villarrubia Jesus , Thurberg Beth L. , Yarramaneni Abhimanyu , Armstrong Nicole M. , Kim Yong , Kumar Monica
Published: December 2023

Background

Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment.

Results

Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event.

Conclusion

Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy.

Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691
Novel 8-Methoxycoumarin-3-Carboxamides with potent anticancer activity against liver cancer via targeting caspase-3/7 and β-tubulin polymerization
Authors: Alzamami Ahmad , Radwan Eman M. , Abo-Elabass Eman , Behery Mohammed El , Alshwyeh Hussah Abdullah , Al-Olayan Ebtesam , Altamimi Abdulmalik S. , Attallah Nashwah G. M. , Altwaijry Najla , Jaremko Mariusz , Saied Essa M.
Published: December 2023

In the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate their antiproliferative activity against liver cancer cells. Toward this, we developed a versatile synthetic approach to produce a series of 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment of their antiproliferative activity demonstrated their significant inhibitory effects on the growth of HepG2 cells, a widely studied liver cancer cell line. Among screened compounds, compound 5 exhibited the most potent antiproliferative activity among the screened compounds (IC50 = 0.9 µM), outperforming the anticancer drug staurosporine (IC50 = 8.4 µM), while showing minimal impact on normal cells. The flow cytometric analysis revealed that compound 5 induces cell cycle arrest during the G1/S phase and triggers apoptosis in HepG2 cells by increasing the percentage of cells arrested in the G2/M and pre-G1 phases. Annexin V-FITC/PI screening further supported the induction of apoptosis without significant necrosis. Further, compound 5 exhibited the ability to activate caspase3/7 protein and substantially inhibited β-tubulin polymerization activity in HepG2 cells. Finally, molecular modelling analysis further affirmed the high binding affinity of compound 5 toward the active cavity of β-tubulin protein, suggesting its mechanistic involvement. Collectively, our findings highlight the therapeutic potential of the presented class of coumarin analogues, especially compound 5, as promising candidates for the development of effective anti-hepatocellular carcinoma agents.
Alterations in lipidome profiles distinguish early-onset hyperuricemia, gout, and the effect of urate-lowering treatment
Authors: Kvasnička Aleš , Friedecký David , Brumarová Radana , Pavlíková Markéta , Pavelcová Kateřina , Mašínová Jana , Hasíková Lenka , Závada Jakub , Pavelka Karel , Ješina Pavel , Stibůrková Blanka
Published: December 2023

Background

Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment (ULT). Our study aimed to evaluate differences in plasma lipidome between patients with asymptomatic HUA detected ≤ 40 years (HUA ≤ 40) and > 40 years, gout patients with disease onset ≤ 40 years (Gout ≤ 40) and > 40 years, and normouricemic healthy controls (HC).

Methods

Plasma samples were collected from 94 asymptomatic HUA (77% HUA ≤ 40) subjects, 196 gout patients (59% Gout ≤ 40), and 53 HC. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied.

Results

Both HUA and gout patients showed alterations in lipid profiles with the most significant upregulation of phosphatidylethanolamines and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls. More profound changes were observed in HUA ≤ 40 and Gout ≤ 40 without ULT. Multivariate statistics differentiated HUA ≤ 40 and Gout ≤ 40 groups from HC with an overall accuracy of > 95%.

Conclusion

Alterations in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism. The most significant glycerophospholipid dysregulation was found in HUA ≤ 40 and Gout ≤ 40 patients, together with a correction of this imbalance with ULT.
Antibiotic-Resistant Arcobacter spp. in commercial and smallholder farm animals in Asante Akim North Municipality, Ghana and Korogwe Town Council, Tanzania: a cross-sectional study
Authors: Paintsil Ellis Kobina , Ofori Linda Aurelia , Akenten Charity Wiafe , Zautner Andreas E. , Mbwana Joyce , Khan Neyaz Ahmed , Lusingu John P. A. , Kaseka Joseph , Minja Daniel T. R. , Gesase Samwel , Jaeger Anna , Lamshöft Maike , May Jürgen , Obiri-Danso Kwasi , Krumkamp Ralf , Dekker Denise
Published: December 2023

Background

Arcobacter species are considered emerging foodborne pathogens that can potentially cause serious infections in animals and humans. This cross-sectional study determined the frequency of potentially pathogenic Arcobacter spp. in both commercial and smallholder farm animals in Ghana and Tanzania. A total of 1585 and 1047 (poultry and livestock) samples were collected in Ghana and Tanzania, respectively. Selective enrichment media, along with oxidase and Gram testing, were employed for isolation of suspected Arcobacter spp. and confirmation was done using MALDI-TOF MS. Antibiotic susceptibility was assessed through disk diffusion method and ECOFFs were generated, for interpretation, based on resulting inhibition zone diameters.

Results

The overall Arcobacter frequency was higher in Ghana (7.0%, n = 111) than in Tanzania (2.0%, n = 21). The frequency of Arcobacter in commercial farms in Ghana was 10.3% (n/N = 83/805), while in Tanzania, it was 2.8% (n/N = 12/430). Arcobacter was detected in only 3.6% (n/N = 28/780) of the samples from smallholder farms in Ghana and 1.5% (n/N = 9/617) of the samples from Tanzania. For commercial farms, in Ghana, the presence of Arcobacter was more abundant in pigs (45.1%, n/N = 37/82), followed by ducks (38.5%, n/N = 10/26) and quails (35.7%, n/N = 10/28). According to MALDI-TOF-based species identification, Arcobacter butzleri (91.6%, n/N = 121/132), Arcobacter lanthieri (6.1%, n/N = 8/132), and Arcobacter cryaerophilus (2.3%, n/N = 3/132) were the only three Arcobacter species detected at both study sites. Almost all of the Arcobacter from Ghana (98.2%, n/N = 109/111) were isolated during the rainy season. The inhibition zone diameters recorded for penicillin, ampicillin, and chloramphenicol allowed no determination of an epidemiological cut-off value. However, the results indicated a general resistance to these three antimicrobials. Multidrug resistance was noted in 57.1% (n/N = 12/21) of the Arcobacter isolates from Tanzania and 45.0% (n/N = 50/111) of those from Ghana. The type of farm (commercial or smallholder) and source of the sample (poultry or livestock) were found to be associated with multi-drug resistance.

Conclusions

The high levels of MDR Arcobacter detected from farms in both countries call for urgent attention and comprehensive strategies to mitigate the spread of antimicrobial resistance in these pathogens.