bluuebunny/crossref_metadata_2025 huggingface dataset:
A formative research to explore the programmatic approach of vaccinating the Rohingya refugees and host communities against COVID-19 infection in Bangladesh
Authors: Chowdhury Anika Tasneem , Kundu Satyajit , Sultana Zeeba Zahra , Hijazi Heba Hesham Ali , Hossain Ahmed
Published: September 2023

Background

The vaccination of the Rohingya refugees and host communities against COVID-19 in Cox’s Bazar started in August 2021. Government authorities and Non-Government Organisation partners implemented a project around the initial period of vaccination to improve awareness and access to target beneficiaries. We conducted formative research to understand the programmatic approach of this project and identify potential challenges and community perceptions regarding immunisation against COVID-19.

Methodology

This was formative research in which we used a qualitative method of data collection. Purposively chosen 12 key-informant interviews and conveniently chosen 20 in-depth interviews were conducted using semi-structured interview guidelines from August to September 2022 in the Rohingya camp and host communities of Cox’s Bazar District, Bangladesh. Ethical approval was obtained from the North South University Institutional Review Board, and written informed consent was obtained from all the participants. We used a thematic analysis approach to analyse the data.

Results

The project neither provided any promotional or tailored messages regarding the COVID-19 vaccine nor conducted any vaccine hesitancy surveys before implementing the project. The project did not provide any storage facilities for the vaccines’ cold chain management but provided transport support to carry the vaccines from the district to the sub-district level. Community leaders were included in the decision-making process during local-level planning of the vaccination programme. The project supported the reporting of any adverse effects following immunisation from community members to the government health authorities. Vaccine hesitancy among participants was high in the early stages, but mass campaigns and vaccination of frontline health workers increased their acceptance. The major challenges reported by the informants were low budget and lower salaries of field staff, stacking of the registration process at the beginning, reluctance of participants, inadequate transportation and manpower, and inadequate baby feeding corners at vaccination centers.

Conclusion

The findings from our study will help policymakers from the Government, the UN, and other humanitarian agencies to adapt and better address the issue of vaccine acceptance and strengthen the vaccination programme.
Beyond rational—biosensor-guided isolation of 100 independently evolved bacterial strain variants and comparative analysis of their genomes
Authors: Baumann Philipp T. , Dal Molin Michael , Aring Hannah , Krumbach Karin , Müller Moritz-Fabian , Vroling Bas , van Summeren-Wesenhagen Philana V. , Noack Stephan , Marienhagen Jan
Published: September 2023

Background

In contrast to modern rational metabolic engineering, classical strain development strongly relies on random mutagenesis and screening for the desired production phenotype. Nowadays, with the availability of biosensor-based FACS screening strategies, these random approaches are coming back into fashion. In this study, we employ this technology in combination with comparative genome analyses to identify novel mutations contributing to product formation in the genome of a Corynebacterium glutamicuml-histidine producer. Since all known genetic targets contributing to l-histidine production have been already rationally engineered in this strain, identification of novel beneficial mutations can be regarded as challenging, as they might not be intuitively linkable to l-histidine biosynthesis.

Results

In order to identify 100 improved strain variants that had each arisen independently, we performed > 600 chemical mutagenesis experiments, > 200 biosensor-based FACS screenings, isolated > 50,000 variants with increased fluorescence, and characterized > 4500 variants with regard to biomass formation and l-histidine production. Based on comparative genome analyses of these 100 variants accumulating 10–80% more l-histidine, we discovered several beneficial mutations. Combination of selected genetic modifications allowed for the construction of a strain variant characterized by a doubled l-histidine titer (29 mM) and product yield (0.13 C-mol C-mol−1) in comparison to the starting variant.

Conclusions

This study may serve as a blueprint for the identification of novel beneficial mutations in microbial producers in a more systematic manner. This way, also previously unexplored genes or genes with previously unknown contribution to the respective production phenotype can be identified. We believe that this technology has a great potential to push industrial production strains towards maximum performance.
Establishment of a large-scale patient-derived high-risk colorectal adenoma organoid biobank for high-throughput and high-content drug screening
Authors: Luo Zhongguang , Wang Bangting , Luo Feifei , Guo Yumeng , Jiang Ning , Wei Jinsong , Wang Xin , Tseng Yujen , Chen Jian , Zhao Bing , Liu Jie
Published: September 2023

Background

Colorectal adenoma (CA), especially high-risk CA (HRCA), is a precancerous lesion with high prevalence and recurrence rate and accounts for about 90% incidence of sporadic colorectal cancer cases worldwide. Currently, recurrent CA can only be treated with repeated invasive polypectomies, while safe and promising pharmaceutical invention strategies are still missing due to the lack of reliable in vitro model for CA-related drug screening.

Methods

We have established a large-scale patient-derived high-risk colorectal adenoma organoid (HRCA-PDO) biobank containing 37 PDO lines derived from 33 patients and then conducted a series of high-throughput and high-content HRCA drug screening.

Results

We established the primary culture system with the non-WNT3a medium which highly improved the purity while maintained the viability of HRCA-PDOs. We also proved that the HRCA-PDOs replicated the histological features, cellular diversity, genetic mutations, and molecular characteristics of the primary adenomas. Especially, we identified the dysregulated stem genes including LGR5, c-Myc, and OLFM4 as the markers of adenoma, which are well preserved in HRCA-PDOs. Based on the HRCA-PDO biobank, a customized 139 compound library was applied for drug screening. Four drugs including metformin, BMS754807, panobinostat and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. As a representative, metformin was discovered to hinder HRCA-PDO growth in vitro and in vivo by restricting the stemness maintenance.

Conclusions

This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer.
Exogenous female sex steroid hormones and new-onset asthma in women: a matched case–control study
Authors: Zhang Guoqiang , Basna Rani , Mathur Maya B. , Lässer Cecilia , Mincheva Roxana , Ekerljung Linda , Wennergren Göran , Rådinger Madeleine , Lundbäck Bo , Kankaanranta Hannu , Nwaru Bright I.
Published: September 2023

Background

Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women.

Methods

We conducted a matched case–control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16–75 years, with 8-year follow-up (2008–2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models.

Results

We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03–4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49–2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79–1.55) and 1.18 (95% PI 0.92–1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%.

Conclusions

Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.
Impacts of the COVID-19 pandemic on access to healthcare among people with disabilities: evidence from six low- and middle-income countries
Authors: Hunt Xanthe , Hameed Shaffa , Tetali Shailaja , Ngoc Luong Anh , Ganle John , Huq Lopita , Shakespeare Tom , Smythe Tracey , Ilkkursun Zeynep , Kuper Hannah , Acarturk Ceren , Kannuri Nanda Kishore , Mai Vu Quynh , Khan Rifat Shahpar , Banks Lena Morgon
Published: September 2023

Background

The pandemic has placed considerable strain on health systems, especially in low- and middle-income countries (LMICs), leading to reductions in the availability of routine health services. Emerging evidence suggests that people with disabilities have encountered marked challenges in accessing healthcare services and supports in the context of the pandemic. Further research is needed to explore specific barriers to accessing healthcare during the pandemic, and any strategies that promoted continued access to health services in LMICs where the vast majority of people with disabilities live.

Methods

Qualitative in-depth interviews were conducted with persons with disabilities in Ghana, Zimbabwe, Viet Nam, Türkiye (Syrian refugees), Bangladesh, and India as part of a larger project exploring the experiences of people with disabilities during the COVID-19 pandemic and their inclusion in government response activities. Data were analysed using thematic analysis.

Results

This research found that people with disabilities in six countries - representing a diverse geographic spread, with different health systems and COVID-19 responses - all experienced additional difficulties accessing healthcare during the pandemic. Key barriers to accessing healthcare during the pandemic included changes in availability of services due to systems restructuring, difficulty affording care due to the economic impacts of the pandemic, fear of contracting coronavirus, and a lack of human support to enable care-seeking.

Conclusion

These barriers ultimately led to decreased utilisation of services which, in turn, negatively impacted their health and wellbeing. However, we also found that certain factors, including active and engaged Organisations of Persons with Disabilities (OPDs) and Non-Governmental Organizations (NGOs) played a role in reducing some of the impact of pandemic-related healthcare access barriers.
Correlation between serum soluble ASGR1 concentration and low-density lipoprotein cholesterol levels: a cross-sectional study
Authors: Luo Qin , Chen Jingfei , Su Yingjie , Wu Panyun , Wang Jiangang , Fang Zhenfei , Luo Fei
Published: September 2023

Background

Recent studies have shown that loss-of-function mutations in hepatic asialoglycoprotein receptor 1 (ASGR1) are associated with low levels of circulating cholesterol and a reduced risk of coronary artery disease (CAD). In contrast to ASGR1 on the hepatocyte membrane, serum soluble ASGR1 (sASGR1) is a secreted form that has been detected in circulation. However, the functions of serum sASGR1 are unclear. This study aims to investigate the relationship between human serum sASGR1 concentration and low-density lipoprotein cholesterol (LDL-C) levels.

Methods

In a cohort of 134 participants who underwent coronary angiography examination, basic information was recorded, and blood samples were collected for biochemical testing. The serum sASGR1 concentration was determined by ELISA kits. The relationship between sASGR1 concentration and LDL-C levels was examined using linear regression models and interaction tests. Univariate and multivariate analyses were used to identify clinical variables that affect sASGR1 levels.

Results

After adjusting for potential confounders such as age, sex, BMI, and statin use, the serum sASGR1 concentration was positively correlated with LDL-C levels (β = 0.093, 95% CI: 0.04 to 0.14, P < 0.001). Subgroup analysis and interaction tests showed that the effect of serum sASGR1 concentration on LDL-C levels was significantly influenced by hypertension status (P for interaction = 0.0067). The results of a multivariate linear regression analysis incorporating age, serum TG, LDL-C, nonesterified fatty acid (NEFA), white blood cell counts (WBCC), and fibrinogen revealed that LDL-C (β = 1.005, 95% CI: 0.35 to 1.66, P = 0.003) and WBCC (β = 0.787, 95% CI: 0.41 to 1.16, P < 0.0001) were independent influencing factors for serum sASGR1 levels.

Conclusions

The serum sASGR1 concentration was positively correlated with LDL-C levels. In addition, hypertension status significantly affected the effect of serum sASGR1 on LDL-C levels. This study provides some research ideas for clinical doctors and researchers, as well as some references for additional research on serum sASGR1.
Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification
Authors: Zheng Ming-Hui , Shan Su-Kang , Lin Xiao , Xu Feng , Wu Feng , Guo Bei , Li Fu-Xing-zi , Zhou Zhi-Ang , Wang Yi , Lei Li-Min , Tang Ke-Xin , Duan Jia-Yue , Wu Yun-Yun , Cao Ye-Chi , Liao Xiao-Bo , Yuan Ling-Qing
Published: September 2023

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.

Graphical Abstract
Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury
Authors: Zhou Heng , Jing Shuili , Xiong Wei , Zhu Yangzhi , Duan Xingxiang , Li Ruohan , Peng Youjian , Kumeria Tushar , He Yan , Ye Qingsong
Published: September 2023

Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.
Degenerated nucleus pulposus cells derived exosome carrying miR-27a-3p aggravates intervertebral disc degeneration by inducing M1 polarization of macrophages
Authors: Zhao Xin , Sun Zhen , Xu Benchi , Duan Wei , Chang Le , Lai Kangwei , Ye Zhengxu
Published: September 2023

Background

Intervertebral disc degeneration (IVDD) is a major contributor to spinal disorders. Previous studies have indicated that the infiltration of immunocytes, specifically macrophages, plays a crucial role in the advancement of IVDD. Exosomes (exo) are believed to play a significant role in intercellular communication. This study aims to investigate the role of exosomes derived from degenerated nucleus pulposus (dNPc) in the process of macrophages M1 polarization.

Methods

Nucleus pulposus (NP) tissue and nucleus pulposus cells (NPc) were collected from patients with intervertebral disc degeneration (IVDD) and idiopathic scoliosis. Immunohistochemistry analysis was performed to determine the number of M1 macrophages in NP tissue. Subsequently, exosomes derived from degenerated NP cells (dNPc-exo) and non-degenerated NP cells (nNPc-exo) were collected and co-cultured with M0 macrophages, which were induced from THP-1 cells. The M1 phenotype was assessed using western blot, flow cytometry, immunofluorescence staining, and qRT-PCR. RNA-sequencing analysis was conducted to examine the expression levels of microRNAs in the dNPc-exo and nNPc-exo groups, and qRT-PCR was performed to investigate the effect pf different microRNA to induce macrophage polarization. Furthermore, western blot and qRT-PCR were employed to demonstrate the regulatory effect of microRNAs carried by dNPc-exo on downstream target signaling pathways in macrophages. Finally, an animal model of IVDD was utilized to investigate the impact of dNPc-exo on inducing M1 polarization of macrophages and its role in the IVDD process.

Results

In this study, we observed an increase in the number of M1 macrophages as the intervertebral disc (IVD) degraded. Additionally, we discovered that dNPc releases exosomes (dNPc-exo) could promote the polarization of macrophages towards the M1 phenotype. Notably, through RNA-sequencing analysis of dNPc-exo and nNPc-exo groups, we identified miR-27a-3p as a highly expressed miRNA in the dNPc-exo group, which significantly influences the induction of M1 polarization of macrophages. And then, we discovered that dNPc-exo has the ability to transport miR-27a-3p and target the PPARγ/NFκB/PI3K/AKT signaling pathway, thereby influencing the M1 polarization of macrophages. We conducted experiments using rat model of IVDD and observed that the exosomes carrying miR-27a-3p actually induced the M1 polarization of macrophages and exacerbated the degradation of IVD.

Conclusion

In conclusion, our findings highlight the significant role of dNPc-exo in IVDD process and provide a basis for further investigation into the mechanism of IVDD and the potential of exosome-based therapy.

Graphic abstract
Contextual factors affecting the implementation of drug checking for harm reduction: a scoping literature review from a North American perspective
Authors: Grace Rose Chloe , Kulbokas Victoria , Carkovic Emir , Lee Todd A. , Pickard A. Simon
Published: September 2023

Background

The opioid epidemic continues to be a significant cause of morbidity and mortality in the US. In 2020, 83% of opioid-related overdose deaths were due to synthetic opioids, such as fentanyl. Drug checking services have been widely implemented as a harm reduction intervention to facilitate the identification of substances in a drug sample. There is a need to inform decision-making on drug checking technologies and service implementation. This research aims to outline contextual considerations for the implementation of a drug checking service.

Methods

A scoping review was conducted using a structured search strategy in PubMed and EMBASE. Articles were independently screened by two reviewers, and included if they were primary literature and reported on an actionable consideration(s) for drug checking services. Data elements were extracted using a standardized form, and included study design, study population, drug checking technology utilized or discussed, and main findings.

Results

Twenty-nine articles were selected for inclusion, and four primary areas of consideration were identified: drug checking technologies, venue of a drug checking service, legality, and privacy. Technological considerations include the need for highly accurate, quantitative results which appeal to both populations of people with drug use disorder and recreational users. Accessibility of services was identified as an important factor that may be impacted by the location, integration with other services, how the service is provided (mobile vs. fixed), and the hours of operation. Maintaining plausible deniability and building trust were seen as important facilitators to service use and engagement. Issues surrounding legality were the most frequently cited barrier by patrons, including fear of criminalization, policing, and surveillance. Patrons and stakeholders identified a need for supportive policies that offer protections. Maintaining anonymity for patrons is crucial to addressing privacy-related barriers.

Conclusion

This review highlights the need to understand the local population and climate for drug checking to implement a drug checking service successfully. Common themes identified in the literature included considerations related to the choice of technology, the type of venue, and the impact of legality and privacy. We intend to utilize these considerations in future research to help guide discussions with US-based stakeholders.
Design, delivery and effectiveness of health practitioner regulation systems: an integrative review
Authors: Leslie Kathleen , Bourgeault Ivy Lynn , Carlton Anne-Louise , Balasubramanian Madhan , Mirshahi Raha , Short Stephanie D. , Carè Jenny , Cometto Giorgio , Lin Vivian
Published: September 2023

Background

Health practitioner regulation (HPR) systems are increasingly recognized as playing an important role in supporting health workforce availability, accessibility, quality, and sustainability, while promoting patient safety. This review aimed to identify evidence on the design, delivery and effectiveness of HPR to inform policy decisions.

Methods

We conducted an integrative analysis of literature published between 2010 and 2021. Fourteen databases were systematically searched, with data extracted and synthesized based on a modified Donabedian framework.

Findings

This large-scale review synthesized evidence from a range of academic (n = 410) and grey literature (n = 426) relevant to HPR. We identified key themes and findings for a series of HPR topics organized according to our structures–processes–outcomes conceptual framework. Governance reforms in HPR are shifting towards multi-profession regulators, enhanced accountability, and risk-based approaches; however, comparisons between HPR models were complicated by a lack of a standardized HPR typology. HPR can support government workforce strategies, despite persisting challenges in cross-border recognition of qualifications and portability of registration. Scope of practice reform adapted to modern health systems can improve access and quality. Alternatives to statutory registration for lower-risk health occupations can improve services and protect the public, while standardized evaluation frameworks can aid regulatory strengthening. Knowledge gaps remain around the outcomes and effectiveness of HPR processes, including continuing professional development models, national licensing examinations, accreditation of health practitioner education programs, mandatory reporting obligations, remediation programs, and statutory registration of traditional and complementary medicine practitioners.

Conclusion

We identified key themes, issues, and evidence gaps valuable for governments, regulators, and health system leaders. We also identified evidence base limitations that warrant caution when interpreting and generalizing the results across jurisdictions and professions. Themes and findings reflect interests and concerns in high-income Anglophone countries where most literature originated. Most studies were descriptive, resulting in a low certainty of evidence. To inform regulatory design and reform, research funders and governments should prioritize evidence on regulatory outcomes, including innovative approaches we identified in our review. Additionally, a systematic approach is needed to track and evaluate the impact of regulatory interventions and innovations on achieving health workforce and health systems goals.
Developing, implementing, and monitoring tailored strategies for integrated knowledge translation in five sub-Saharan African countries
Authors: Sell Kerstin , Jessani Nasreen S. , Mesfin Firaol , Rehfuess Eva A. , Rohwer Anke , Delobelle Peter , Balugaba Bonny E. , Schmidt Bey-Marrié , Kedir Kiya , Mpando Talitha , Niyibizi Jean Berchmans , Osuret Jimmy , Bayiga-Zziwa Esther , Kredo Tamara , Mbeye Nyanyiwe Masingi , Pfadenhauer Lisa M.
Published: September 2023

Background

Integrated knowledge translation (IKT) through strategic, continuous engagement with decision-makers represents an approach to bridge research, policy and practice. The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA +), comprising research institutions in Ethiopia, Malawi, Rwanda, South Africa, Uganda and Germany, developed and implemented tailored IKT strategies as part of its multifaceted research on prevention and care of non-communicable diseases and road traffic injuries. The objective of this article is to describe the CEBHA + IKT approach and report on the development, implementation and monitoring of site-specific IKT strategies.

Methods

We draw on findings derived from the mixed method IKT evaluation (conducted in 2020–2021), and undertook document analyses and a reflective survey among IKT implementers. Quantitative data were analysed descriptively and qualitative data were analysed using content analysis. The authors used the TIDieR checklist to report results in a structured manner.

Results

Preliminary IKT evaluation data (33 interviews with researchers and stakeholders from policy and practice, and 31 survey responses), 49 documents, and eight responses to the reflective survey informed this article. In each of the five African CEBHA + countries, a site-specific IKT strategy guided IKT implementation, tailored to the respective national context, engagement aims, research tasks, and individuals involved. IKT implementers undertook a variety of IKT activities at varying levels of engagement that targeted a broad range of decision-makers and other stakeholders, particularly during project planning, data interpretation, and output dissemination. Throughout the project, the IKT teams continued to tailor IKT strategies informally and modified the IKT approach by responding to ad hoc engagements and involving non-governmental organisations, universities, and communities. Challenges to using systematic, formalised IKT strategies arose in particular with respect to the demand on time and resources, leading to the modification of monitoring processes.

Conclusion

Tailoring of the CEBHA + IKT approach led to the inclusion of some atypical IKT partners and to greater responsiveness to unexpected opportunities for decision-maker engagement. Benefits of using systematic IKT strategies included clarity on engagement aims, balancing of existing and new strategic partnerships, and an enhanced understanding of research context, including site-specific structures for evidence-informed decision-making.
Retinoblastoma: present scenario and future challenges
Authors: Byroju Vishnu Vardhan , Nadukkandy Aisha Shigna , Cordani Marco , Kumar Lekha Dinesh
Published: September 2023

With an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma.
Investigating the potential of oncolytic viruses for cancer treatment via MSC delivery
Authors: Ghaleh Hadi Esmaeili Gouvarchin , Vakilzadeh Gazal , Zahiri Ali , Farzanehpour Mahdieh
Published: September 2023

Mesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration. MSCs possess the unique ability to selectively migrate to tumors, making them an excellent candidate for targeted delivery of oncolytic viruses (OVs) to treat isolated tumors and metastatic malignancies. OVs have attracted attention as a potential treatment for cancer due to their ability to selectively infect and destroy tumor cells while sparing normal cells. In addition, OVs can induce immunogenic cell death and contain curative transgenes in their genome, making them an attractive candidate for cancer treatment in combination with immunotherapies. In combination with MSCs, OVs can modulate the tumor microenvironment and trigger anti-tumor immune responses, making MSC-releasing OVs a promising approach for cancer treatment. This study reviews researches on the use of MSC-released OVs as a novel method for treating cancer.

Graphical Abstract
Educational inequalities in metabolic syndrome prevalence, timing, and duration amongst adults over the life course: a microsimulation analysis based on the lifelines cohort study
Authors: Hoveling Liza A. , Lepe Alexander , Boissonneault Michael , de Beer Joop A. A. , Smidt Nynke , de Kroon Marlou L. A. , Liefbroer Aart C.
Published: September 2023

Background

Educational inequalities in metabolic syndrome (MetS) are a growing public health concern. Intervening on modifiable factors may help reduce these inequalities, but there is a need for evidence on the long-term impact of intervening on these factors. Thus, we simulate the development of educational inequalities in MetS across the life course and assess the impact of intervening on the modifiable factors that contribute to these inequalities.

Methods

We used data from the prospective multigenerational Dutch Lifelines Cohort Study to estimate the required input for a continuous-time microsimulation. The microsimulation projects the development of educational inequalities in MetS between ages 18 and 65, and assesses the potential benefit of intervening on smoking, alcohol use, diet quality, and health literacy.

Findings

The likelihood of ever experiencing MetS between ages 18 and 65 varies from 32.5% among high educated women to 71.5% among low educated men. On average, 27.6% more individuals with low education will ever experience MetS between ages 18 and 65 compared to those with high education. Additionally, individuals with low education generally will develop MetS 2.3 years earlier, and will spend an extra 2.6 years with MetS, compared to individuals with high education. Changes to smoking behaviours in individuals with low education produced the largest effect; it would reduce inequalities in prevalence, timing and duration by an average of 7.5%, 9.5%, and 6.9%, respectively.

Conclusions

Interventions targeting the modifiable factors included in this study, especially smoking, could help reduce the estimated educational inequalities in MetS over the life course.
Gender differences in the distribution of children’s physical activity: evidence from nine countries
Authors: Kretschmer Luke , Salali Gul Deniz , Andersen Lars Bo , Hallal Pedro C. , Northstone Kate , Sardinha Luís B. , Dyble Mark , Bann David ,   International Children’s Accelerometry Database (ICAD) Collaborators, Andersen L. B. , Anderssen S. , Cardon G. , Davey R. , Jago R. , Janz K. F. , Kriemler S. , Møller N. , Northstone K. , Pate R. , Puder J. J. , Reilly J. , Salmon J. , Sardinha L. B. , van Sluijs E. M. F.
Published: September 2023

Background

Physical activity in childhood is thought to influences health and development. Previous studies have found that boys are typically more active than girls, yet the focus has largely been on differences in average levels or proportions above a threshold rather than the full distribution of activity across all intensities. We thus examined differences in the distribution of physical activity between girls and boys in a multi-national sample of children.

Methods

We used the harmonised International Children Accelerometry Database (ICAD), including waist-worn accelerometry data from 15,461 individuals (Boys: 48.3%) from 9 countries. Employing Generalised Additive Models of Location, Shape, and Scale (GAMLSS) we investigated gender differences in the distribution of individuals, including comparisons of variability (SD) and average physical activity levels (mean and median) and skewness. We conducted this analysis for each activity intensity (Sedentary, Light, and Moderate-to-Vigorous (MVPA)) and a summary measure (counts per minute (CPM)).

Results

Sizable gender differences in the distribution of activity were found for moderate to vigorous activity and counts per minute, with boys having higher average levels (38% higher mean volumes of MVPA, 20% higher CPM), yet substantially more between-person variability (30% higher standard deviation (SD) for MVPA, 17% higher SD for CPM); boys’ distributions were less positively skewed than girls. Conversely, there was little to no difference between girls and boys in the distribution of sedentary or light-intensity activity.

Conclusions

Inequality in activity between girls and boys was driven by MVPA. The higher mean volumes of MVPA in boys occurred alongside greater variability. This suggests a need to consider the underlying distribution of activity in future research; for example, interventions which target gender inequality in MVPA may inadvertently lead to increased inequality within girls.
Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study
Authors: Pellegrino Raffaello , Paganelli Roberto , Di Iorio Angelo , Bandinelli Stefania , Moretti Antimo , Iolascon Giovanni , Sparvieri Eleonora , Tarantino Domiziano , Ferrucci Luigi
Published: September 2023

Background

Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years’ follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population.

Methods

The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session.

Results

The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants.

Conclusion

NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.
Generating synthetic gait patterns based on benchmark datasets for controlling prosthetic legs
Authors: Kim Minjae , Hargrove Levi J.
Published: September 2023

Background

Prosthetic legs help individuals with an amputation regain locomotion. Recently, deep neural network (DNN)-based control methods, which take advantage of the end-to-end learning capability of the network, have been proposed. One prominent challenge for these learning-based approaches is obtaining data for the training, particularly for the training of a mid-level controller. In this study, we propose a method for generating synthetic gait patterns (vertical load and lower limb joint angles) using a generative adversarial network (GAN). This approach enables a mid-level controller to execute ambulation modes that are not included in the training datasets.

Methods

The conditional GAN is trained on benchmark datasets that contain the gait data of individuals without amputation; synthetic gait patterns are generated from the user input. Further, a DNN-based controller for the generation of impedance parameters is trained using the synthetic gait pattern and the corresponding synthetic stiffness and damping coefficients.

Results

The trained GAN generated synthetic gait patterns with a coefficient of determination of 0.97 and a structural similarity index of 0.94 relative to benchmark data that were not included in the training datasets. We trained a DNN-based controller using the GAN-generated synthetic gait patterns for level-ground walking, standing-to-sitting motion, and sitting-to-standing motion. Four individuals without amputation participated in bypass testing and demonstrated the ambulation modes. The model successfully generated control parameters for the knee and ankle based on thigh angle and vertical load.

Conclusions

This study demonstrates that synthetic gait patterns can be used to train DNN models for impedance control. We believe a conditional GAN trained on benchmark datasets can provide reliable gait data for ambulation modes that are not included in its training datasets. Thus, designing gait data using a conditional GAN could facilitate the efficient and effective training of controllers for prosthetic legs.
Minimally invasive medial femoral approach to total knee arthroplasty improves short-term outcomes compared to the standard medial parapatellar approach: a systematic review and meta-analysis
Authors: Yang Xin , Cheng Qing-hao , Yang Yong-ze , Zhang An-ren , Fan Hua , Guo Hong-zhang
Published: September 2023

Objective

The aim of this study is to conduct a comprehensive evaluation of the effectiveness of the medial parapatellar approach via the vastus medialis obliquus muscle in comparison with the standard medial parapatellar approach for total knee arthroplasty, using a systematic approach.

Methods

A computer search was conducted on PubMed, EMBASE, Medline, Cochrane libraries, and Web of Science databases to comprehensively collect randomized controlled studies on minimally invasive (MMV) approaches for knee arthroplasty, specifically the vastus and medial parapatellar (MP) approaches. Two authors independently screened the literature based on inclusion and exclusion criteria, evaluated the quality of the included studies using the Cochrane systematic review method, and performed a meta-analysis using RevMan 5.3 software.

Results

A total of twelve randomized controlled studies were ultimately included, comprising 788 knees. The small incision medial femoral muscle approach (MMV) group consisted of 398 cases, while the traditional parapatellar approach (MP) group consisted of 390 cases. Data analysis showed that in the comparison of KSS, VAS, and ROM score at 3 months after surgery, MMV approach was superior to MP approach [MD = 2.89, 95%CI (0.33, 5.46), P = 0.03], [MD = − 0.22, 95%CI (− 0.36, − 0.09), P = 0.001], and [MD = 1.08, 95%CI (0.04, 2.12), P = 0.04]. However, there was no significant difference in the postoperative KSS, VAS, and ROM score between the MMV and MP approaches at 6 and 12 months after surgery. The operation time of the MMV group was longer than that of the MP group [MD = 8.98, 95%CI (4.64, 13.32), P < 0.0001], and the number of days of straight leg raising after surgery was shorter in the MMV group than in the MP group [MD = − 1.91, 95%CI (− 3.45, − 0.37), P = 0.01], with statistically significant differences. There was no significant difference in the lateral support band release rate [OR = 0.72, 95%CI (0.23, 2.28), P = 0.58], length of hospital stay [MD = 0.07, 95%CI (− 0.18, 0.31), P = 0.58], postoperative complications [MD = 0.62, 95%CI (0.33, 1.18), P = 0.15], and intraoperative blood loss [MD = 70.50, 95%CI (− 57.51, 198.72), P = 0.28].

Conclusion

Most of the approaches have similar length of stay and incidence of complications compared to standard approaches. However, the minimally invasive midvastus approach has shown potential to improve short-term outcomes.

Study registration: PROSPERO registration number CRD42023410583.
Short-term clinical efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion versus minimally invasive transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: a systematic review and meta-analysis
Authors: Han Hao , Song Yifan , Li Yiming , Zhou Hengcai , Fu Yufei , Li Jie
Published: September 2023

Background

The aim of this study was to comprehensively evaluate the short-term clinical efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) versus minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar degenerative diseases by meta-analysis.

Methods

A computer-based search of PubMed, Embase, Web of Science, Cochrane Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Science and Technology Journal Database (VIP) was conducted from the inception of the each database to April 2023. The searched literature was then screened according to strict inclusion and exclusion criteria. The critical data were extracted and analyzed using Review Manager software5.4.1. Pooled effects were calculated on the basis of data attributes by mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). The Newcastle–Ottawa Scale was used to assess the quality of the studies.

Results

A total of 13 studies and 949 patients met the inclusion criteria for this meta-analysis, 445 in the UBE-LIF group and 504 in the MIS-TLIF group. UBE-TLIF was superior to MIS-TLIF in terms of intraoperative blood flow, postoperative drainage flow, duration of hospital stay, VAS score for low back pain and ODI score, but the operative time was longer than MIS-TLIF group. There were no significant differences between the two groups in terms of total complication rate, modified Macnab grading criteria, fusion rate, VAS score of leg pain, lumbar lordosis, intervertebral disk height.

Conclusion

Both UBE-TLIF and MIS-TLIF are effective surgical modalities for the treatment of degenerative lumbar spine diseases. They have similar treatment outcomes, but UBE-TLIF has the advantages of less intraoperative blood loss, shorter postoperative hospital stay, and faster recovery.

Trial registration: This study has been registered at INPLASY.COM (No. INPLASY202320087).