bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a free lending of sports and leisure equipment service: a cross-sectional survey exploring user characteristics, utilization patterns, and significance among children and youth
Authors: Högman Johan , Wagnsson Stefan , Bellander Sebastian
Published: July 2024

Background

The escalating costs of sports equipment, coupled with socioeconomic disparities, hinder children’s participation in physical activities. The Leisure Equipment Library (LEL), a unique service in Sweden, addresses this challenge by providing free equipment lending. This study investigated the significance of providing free lending of sports and recreational equipment for children’s and youth’s opportunities to engage in physical activities during leisure time.

Method

Utilizing a cross-sectional survey during the summer-2022 period, the study is based on data from 427 LEL users aged 7 to 25 years. User characteristics (demography, socioeconomic status, physical activity profiles), equipment usage patterns and perceived significance are also analyzed. The findings are discussed using the concept of consumer-brand identification.

Results

The results showed that LEL reaches a broad and diverse group of children and young people in terms of gender, age, socioeconomic status, and physical activity profile. The borrowed equipment, primarily used for play and recreation, serves as an essential resource for children and youths and, in particular, for those with low socioeconomic status. LEL is considered highly important by all user groups, with a majority emphasizing its significance in facilitating leisure activities.

Conclusions

The study suggests LEL’s success lies in its accessibility and that users identify with the brand of LEL. Users perceive LEL as a service catering to various recreational needs rather than sports, fostering inclusivity. The localization of stores in various types of areas, combined with high-quality products, enable children and young people from different socioeconomic areas to use the service. LEL’s success hinges on maintaining a positive brand image and promoting a recreation-oriented identity. Opportunities exist to strengthen emotional bonds with users, enhance branding strategies, and position LEL as a valuable resource for inclusive recreational activities. In conclusion, this study highlights the potential of free lending services, such as LEL, to bridge socioeconomic gaps in the promotion of physical activity among children and young people.
Analysis of the characteristics, efficiency, and influencing factors of third-party mediation mechanisms for resolving medical disputes in public hospitals in China
Authors: Shen Yanfei , Li Gaiyun , Tang Zhiguo , Wang Qi , Zhang Zurong , Hao Xiangyong , Han Xuemei
Published: July 2024

Background

Medical disputes, which are prevalent in China, are a growing global public health problem. The Chinese government has proposed third-party mediation (TPM) to resolve this issue. However, the characteristics, efficiency, and influencing factors of TPM in resolving medical disputes in public hospitals in China have yet to be determined.

Methods

We conducted a systematic study using TPM records from medical disputes in Gansu Province in China from 2014 to 2019. A χ2 test was used to compare differences between groups, and binary logistic analysis was performed to determine the factors influencing the choice of TPM for resolving medical disputes.

Results

We analyzed 5,948 TPM records of medical disputes in Gansu Province in China. The number of medical disputes and the amount of compensation awarded in public hospitals in the Gansu Province increased annually from 2014 to 2019, with most of the disputes occurring in secondary and tertiary hospitals. Approximately 89.01% of the medical disputes were handled by TPM; the average compensation amount with TPM was Chinese Yuan (CNY) 48,688.73, significantly less than that awarded via court judgment and judicial mediation. TPM was more likely to succeed in settling medical disputes in the < CNY10,000 compensation group than in the no-compensation group (odds ratio [OR] = 3.14, 95% confidence interval [CI] 1.53–6.45). However, as the compensation amount increased, the likelihood of choosing TPM decreased significantly. Moreover, TPM was less likely to be chosen when medical disputes did not involve death (OR = 0.49, 95% CI 0.36–0.45) or when no-fault liability was determined (vs. medical accidents; OR = 0.37, 95% CI 0.20–0.67).

Conclusion

Our findings demonstrate that TPM mechanisms play a positive role in efficiently reducing compensation amounts and increasing medical dispute resolution rates which was the main settlement method in resolving medical disputes in public hospitals of Gansu Province in China. TPM could help greatly reduce conflicts between doctors and patients, avoid litigation, and save time and costs for both parties. Moreover, compensation amounts, non-fatal outcomes, and no-fault liability determinations influence the choice of TPM for settling medical disputes.
Operative treatment of isolated epiphyseal fracture of the distal fibula: 1 case report and literature review
Authors: Jiang Zhongbo , Yue Liang , Wang Deheng , Liang Yanchen , Jing Cheng , Guo Yanbo
Published: July 2024

Pediatric ankle injuries are common; ankle epiphyseal fractures are also common in children. But isolated distal epiphyseal fibular fractures of the distal fibula are clinically rare. We describe one unusual case of an adolescent with a completely displaced Salter-Harris type II distal fibular epiphyseal fracture. The attempt of closed reduction failed, and the patient required open reduction and internal fixation. The localized periosteum and the superior peroneal retinaculum were avulsed from the distal fibular metaphysis, with the peroneal tendons underneath exposed but no obvious subluxation. To the best of our knowledge, this combination of injuries has not been previously reported.
Readiness for advance care planning and related factors in the general population: a cross sectional study in Iran
Authors: Askari Ali , Roshan Hosein Mohammadi , Abbaszadeh Nasim , Salesi Mahmood , Hosseini Seyed Morteza , Golmohammadi Mobina , Barasteh Salman , Nademi Omid , Mashayekh Razieh , Sadeghi Mohammad Hossein
Published: July 2024

Context

Advance Care Planning (ACP), as a process for expressing and recording patients' preferences about end-of-life care, has received increasing attention in recent years. However, implementing ACP has been challenging in Iran.

Objectives

To assess the readiness for advance care planning and related factors in the general population of Iran.

Methods

This cross-sectional study was conducted on the general population of Iran in 2022. The data was collected using demographic information questionnaire and The RACP Scale. The purpose and methodology of the research was explained to all participants, and upon their agreement an informed consent was obtained. Participants were invited to fill out the questionnaires wherever is more convenient for them, either alone or if needed, with the help of the researcher to protect their privacy. Chi-square, fisher exact test and multiple logistic Regression model were used to assess the effective factors on the RACP. The data were analyzed by SPSS software version 26.

Results

A total of 641 people with an average age of 36.85 ± 12.05 years participated in this study. Of those, 377 (58.8%) had high RACP. The logistics model showed an association between the chance of readiness for receiving ACP with participants’ education level, such that the chance of readiness in those with Master's or Ph.D. degrees was three times higher than those with a diploma (p = 0.00, OR:3.178(1.672, 6.043)). However, the chances of readiness in those with bachelor’s degrees was not significantly different from those with a diploma (p = 0.936, OR: 0.984 (0.654, 1.479)). Moreover, the chance of readiness was 1.5 higher in participants over 40 years of age compared with participants under the age of 40 (P = 0.01, OR: 1.571(1.10, 2.23)).

Conclusion

According to the findings of this study, it can be concluded that there is a relatively RACP among people in Iranian society. The readiness of individuals for ACP increases by their age and education level. Therefore, by holding appropriate training intervention, we can increase the readiness of the public for ACP to improve their end-of-life outcome.
Academic resilience in nusing students: a concept analysis
Authors: Shen Yang , Feng Hanbo , Li Xiaohan
Published: July 2024

Background

Academic resilience is a crucial concept for nursing students to cope with academic challenges. Currently, there is significant variation in the description of the concept attributes of academic resilience among nursing students, which impedes the advancement of academic research. Therefore, it is essential to establish a clear definition of the concept of academic resilience for nursing students.

Purpose

The purpose of this paper is to report the results of concept analysis of academic resilience of nursing students.

Methods

The Rodgers evolutionary concept analysis was employed to test the attributes, antecedents, consequences and related concepts of academic resilience of nursing students. Walker and Avant’s method was utilized to construct a model case and provide empirical referents.

Results

The findings indicate that the attributes of nursing students’ academic resilience include self-efficacy, self-regulation and recovery, and the antecedents include internal factors and external environmental factors. The consequences include adaptability, career maturity, adversity quotient level, probability of academic success, a sense of belonging to school and low levels of psychological distress.

Conclusion

The systematic understanding of academic resilience among nursing students provides a pathway for nursing educators and students to enhance academic resilience, promote academic success, and establish a foundation for the training of more qualified nurses.
Patient-centered discharge summaries to support safety and individual health literacy: a double-blind randomized controlled trial in Austria
Authors: Schwarz Christine Maria , Hoffmann Magdalena , Smolle Christian , Borenich Andrea , Fürst Stefan , Tuca Alexandru-Cristian , Holl Anna Katharina , Gugatschka Markus , Grogger Victor , Kamolz Lars-Peter , Sendlhofer Gerald
Published: July 2024

Background

To ensure a safe patient discharge from hospital it is necessary to transfer all relevant information in a discharge summary (DS). The aim of this study was to evaluate a bundle of measures to improve the DS for physicians, nurses and patients.

Methods

In a double-blind, randomized, controlled trial, four different versions of DS (2 original, 2 revised) were tested with physicians, nurses and patients. We used an evaluation sheet (Case report form, CRF) with a 6-point Likert scale (1 = completely agree; 6 = strongly disagree).

Results

In total, 441 participants (physicians n = 146, nurses n = 140, patients n = 155) were included in the study. Overall, the two revised DS received significant better ratings than the original DS (original 2.8 ± 0.8 vs. revised 2.1 ± 0.9, p < 0.001). Detailed results for the main domains are structured DS (original 1.9 ± 0.9 vs. revised 2.2 ± 1.3, p = 0.015), content (original 2.7 ± 0.9 vs revised 2.0 ± 0.9, p < 0.001) and comprehensibility (original 3.8 ± 1.2vs. revised 2.3 ± 1.2, p < 0.001).

Conclusion

With simple measures like avoiding abbreviations and describing indications or therapies with fixed contents, the DS can be significantly improved for physicians, nurses and patients at the same time.

Trial registration

First registration 13/11/2020 NCT04628728 at www.clinicaltrials.gov, Update 15/03/2023.
Perceived barriers and opportunities of providing quality family planning services among Palestinian midwives, physicians and nurses in the West Bank: a qualitative study
Authors: Hassan Sahar , Masri Hadeel , Sawalha Isra’ , Mortensen Berit
Published: July 2024

Background

Despite advancements in family planning (FP) services, several barriers persist in the Occupied Palestinian territory (oPt), blocking women’s access to suitable, high-quality and equitable FP services. The aim of this study was to understand how healthcare providers perceive their abilities, barriers and opportunities in providing good quality FP services. Furthermore, it seeks to explore knowledge and training regarding FP among healthcare providers engaged in providing FP services.

Methods

A qualitative study was undertaken from August to September 2022 in seven Primary Health Care (PHC) clinics distributed in three governorates and operating under the Palestinian Ministry of Health (MoH) in the West Bank. Semi-structured, in-depth face-to-face interviews were conducted with 13 health providers (Physicians, midwives and nurses), using an interview guide in Arabic language. Transcripts were subsequently analyzed using the six phases of reflexive thematic analysis.

Results

FP services face various challenges, including shortages in resources such as staff, supplies, infrastructures and FP methods. Midwives possess significant potentials to offer accessible, high-quality, efficient and equitable FP services, yet, their capacities remain underutilized, representing a missed opportunity for a country like Palestine. The study provided a current overview of FP services while illustrating the need for quality FP services and the need for an updated continuous education and training, updated standardized guidelines and protocols and supportive supervision are needed across all levels of healthcare providers. Finally, providers reported a wide range of structural barriers to FP services.

Conclusions

It is crucial to meticulously address both community-related and health system factors to enhance the fulfillment of FP needs and reduce unintended and closely spaced pregnancies. Policymakers should invest in the development of laws and regulations regarding FP services, promoting a comprehensive and holistic approach to FP services. This includes formulating supportive policies, capacity building of human resources and maintaining security of FP commodities.
Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time
Authors: Ndiaye Yaye D. , Wong Wesley , Thwing Julie , Schaffner Stephen F. , Brenneman Katelyn Vendrely , Tine Abdoulaye , Diallo Mamadou A. , Deme Awa B. , Sy Mouhamad , Bei Amy K. , Thiaw Alphonse B. , Daniels Rachel , Ndiaye Tolla , Gaye Amy , Ndiaye Ibrahima M. , Toure Mariama , Gadiaga Nogaye , Sene Aita , Sow Djiby , Garba Mamane N. , Yade Mamadou S. , Dieye Baba , Diongue Khadim , Zoumarou Daba , Ndiaye Aliou , Gomis Jules F. , Fall Fatou B. , Ndiop Medoune , Diallo Ibrahima , Sene Doudou , Macinnis Bronwyn , Seck Mame C. , Ndiaye Mouhamadou , Ngom Bassirou , Diedhiou Younouss , Mbaye Amadou M. , Ndiaye Lamine , Sy Ngayo , Badiane Aida S. , Hartl Daniel L. , Wirth Dyann F. , Volkman Sarah K. , Ndiaye Daouda
Published: July 2024

Background

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance.

Methods

Data from two decades (2000–2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics.

Results

This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014.

Discussion (Conclusion)

The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.
Deployment of attractive targeted sugar baits in western Zambia: installation, monitoring, removal, and disposal procedures during a Phase III cluster randomized controlled trial
Authors: Orange Erica , Kyomuhangi Irene , Masuzyo Mundia , Mwenya Mwansa , Mambo Patricia , Saili Kochelani , Chishya Chama , Chanda Javan , Ashton Ruth A. , Eisele Thomas P. , Yukich Joshua , Miller John , Silumbe Kafula , Hamainza Busiku , Wagman Joseph , Arnzen Annie , Harris Angela F. , Entwistle Julian , Slutsker Laurence , Burkot Thomas R. , Littrell Megan
Published: July 2024

Background

Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement.

Methods

ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission.

Results

A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition.

Discussion

ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy.

Conclusions

Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.
Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach
Authors: Maleki Mohammad Hasan , Vakili Omid , Tavakoli Ramin , Nadimi Elham , Noori Zahra , Taghizadeh Motahareh , Dehghanian Amirreza , Tayebi Lobat , Shafiee Sayed Mohammad
Published: July 2024

Background

Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis.

Methods

Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure.

Results

Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin.

Conclusion

These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.
Endothelial cells-derived exosomes-based hydrogel improved tendinous repair via anti-inflammatory and tissue regeneration-promoting properties
Authors: Dou Yichen , Zhai Hong , Li Haiqiu , Xing Hanlin , Zhu Cheng , Xuan Zhaopeng
Published: July 2024

Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair.In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon’s mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery.Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries.
IPSC-NSCs-derived exosomal let-7b-5p improves motor function after spinal cord Injury by modulating microglial/macrophage pyroptosis
Authors: Liu Jie , Kong Guang , Lu Chenlin , Wang Juan , Li Wenbo , Lv Zhengming , Tong Jian , Liu Yuan , Xiong Wu , Li Haijun , Fan Jin
Published: July 2024

Background

Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms.

Methods

iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP.

Results

Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI.

Conclusion

In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.
Inflammatory biomarkers may be associated with poor outcomes after mechanical thrombectomy
Authors: Wang Hong , Tian Xiaobing , Liao Zhangyuan , Yue Xuanye , Sun Libin , Li Xingrong , Zou Ming , Ding Jiayue
Published: July 2024

Background

Mechanical thrombectomy (MT) has become the mainstay of treatment for acute ischemic stroke (AIS) recently. This case-control study aimed to identify the pivotal role of inflammation in the prognosis of AIS patients after MT.

Methods

Altogether, 70 AIS patients who underwent MT were retrospectively recruited for this study. Receiver operating characteristic analysis was performed to demonstrate the sensitivity and specificity of the inflammatory variables for predicting prognosis. A meta-analysis was performed to pool the published results together. Stata software was used for analysis.

Results

There was no differences in pre-MT inflammatory biomarkers between patients who survived and those who died, as well as patients with modified Rankin Scale (mRS) 0–2 and mRS ≥ 3. In contrast, post-MT C-reactive protein (CRP) levels might be a potential parameter to predict death after thrombectomy [area under the curve (AUC), 95%confidence interval (CI), 0.737, 0.587–0.887; p = 0.005; optimal cutoff value = 4.565]. Moreover, post-MT monocyte count might be an appropriate parameter to predict poor long-term prognosis after thrombectomy (AUC, 95%CI, 0.704, 0.575–0.833; p = 0.017; optimal cutoff value = 0.345). A meta-analysis revealed that the pre-MT inflammatory indices, including white blood cell count (weighted mean difference, 95%CI, 1.32, 1.01—1.63), neutrophil count (1.23, 0.95—1.51), monocyte count (0.05, 0.02—0.09), neuthrophil-to-lymphocyte ratio (2.42, 1.98—2.87) and platelet-to-lymphocyte ratio (24.65, 7.99—41.32), were higher in patients with 3-month mRS ≥ 3, and the lymphocyte count (−0.31,−0.43 to −0.18) was lower in this cohort.

Conclusions

Inflammatory indices were significantly associated with the prognosis of patients undergoing MT, especially post-MT CRP and monocyte count, which can predict long-term outcomes.
Behaviour change interventions to improve physical activity in adults: a systematic review of economic evaluations
Authors: Barrett Stephen , Begg Stephen , Lawrence Jack , Barrett Gabrielle , Nitschke Josh , O’Halloran Paul , Breckon Jeff , Pinheiro Marina De Barros , Sherrington Catherine , Doran Chris , Kingsley Michael
Published: July 2024

Background

Behaviour change interventions can result in lasting improvements in physical activity (PA). A broad implementation of behaviour change interventions are likely to be associated with considerable additional costs, and the evidence is unclear whether they represent good value for money. The aim of this study was to investigate costs and cost-effectiveness of behaviour change interventions to increase PA in community-dwelling adults.

Methods

A search for trial-based economic evaluations investigating behaviour change interventions versus usual care or alternative intervention for adults living in the community was conducted (September 2023). Studies that reported intervention costs and incremental cost-effectiveness ratios (ICERs) for PA or quality-adjusted life years (QALYs) were included. Methodological quality was assessed using the Consensus Health Economic Criteria (CHEC-list). A Grading of Recommendations Assessment, Development and Evaluation style approach was used to assess the certainty of evidence (low, moderate or high certainty).

Results

Sixteen studies were included using a variety of economic perspectives. The behaviour change interventions were heterogeneous with 62% of interventions being informed by a theoretical framework. The median CHEC-list score was 15 (range 11 to 19). Median intervention cost was US$313 per person (range US$83 to US$1,298). In 75% of studies the interventions were reported as cost-effective for changes in PA (moderate certainty of evidence). For cost per QALY/gained, 45% of the interventions were found to be cost-effective (moderate certainty of evidence). No specific type of behaviour change intervention was found to be more effective.

Conclusions

There is moderate certainty that behaviour change interventions are cost-effective approaches for increasing PA. The heterogeneity in economic perspectives, intervention costs and measurement should be considered when interpreting results. There is a need for increased clarity when reporting the functional components of behaviour change interventions, as well as the costs to implement them.
IκBα kinase inhibitor BAY 11-7082 promotes anti-tumor effect in RAS-driven cancers
Authors: Guruvaiah Praveen , Gupta Romi
Published: July 2024

Background

Oncogenic mutations in the RAS gene are associated with uncontrolled cell growth, a hallmark feature contributing to tumorigenesis. While diverse therapeutic strategies have been diligently applied to treat RAS-mutant cancers, successful targeting of the RAS gene remains a persistent challenge in the field of cancer therapy. In our study, we discover a promising avenue for addressing this challenge.

Methods

In this study, we tested the viability of several cell lines carrying oncogenic NRAS, KRAS, and HRAS mutations upon treatment with IkappaBalpha (IκBα) inhibitor BAY 11-7082. We performed both cell culture-based viability assay and in vivo subcutaneous xenograft-based assay to confirm the growth inhibitory effect of BAY 11-7082. We also performed large RNA sequencing analysis to identify differentially regulated genes and pathways in the context of oncogenic NRAS, KRAS, and HRAS mutations upon treatment with BAY 11-7082.

Results

We demonstrate that oncogenic NRAS, KRAS, and HRAS activate the expression of IκBα kinase. BAY 11-7082, an inhibitor of IκBα kinase, attenuates the growth of NRAS, KRAS, and HRAS mutant cancer cells in cell culture and in mouse model. Mechanistically, BAY 11-7082 inhibitor treatment leads to suppression of the PI3K-AKT signaling pathway and activation of apoptosis in all RAS mutant cell lines. Additionally, we find that BAY 11-7082 treatment results in the downregulation of different biological pathways depending upon the type of RAS protein that may also contribute to tumor growth inhibition.

Conclusion

Our study identifies BAY 11-7082 to be an efficacious inhibitor for treating RAS oncogene (HRAS, KRAS, and NRAS) mutant cancer cells. This finding provides new therapeutic opportunity for effective treatment of RAS-mutant cancers.
A novel CAF-cancer cell crosstalk-related gene prognostic index based on machine learning: prognostic significance and prediction of therapeutic response in head and neck squamous cell carcinoma
Authors: Xu Yuming , Li Junda , Wang Jinming , Deng Feilong
Published: July 2024

Background

Cancer-associated fibroblast (CAF)-cancer cell crosstalk (CCCT) plays an important role in tumor microenvironment shaping and immunotherapy response. Current prognostic indexes are insufficient to accurately assess immunotherapy response in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to develop a CCCT-related gene prognostic index (CCRGPI) for assessing the prognosis and response to immune checkpoint inhibitor (ICI) therapy of HNSCC patients.

Methods

Two cellular models, the fibroblast-cancer cell indirect coculture (FCICC) model, and the fibroblast-cancer cell organoid (FC-organoid) model, were constructed to visualize the crosstalk between fibroblasts and cancer cells. Based on a HNSCC scRNA-seq dataset, the R package CellChat was used to perform cell communication analysis to identify gene pairs involved in CCCT. Least absolute shrinkage and selection operator (LASSO) regression was then applied to further refine the selection of these gene pairs. The selected gene pairs were subsequently subjected to stepwise regression to develop CCRGPI. We further performed a comprehensive analysis to determine the molecular and immune characteristics, and prognosis associated with ICI therapy in different CCRGPI subgroups. Finally, the connectivity map (CMap) analysis and molecular docking were used to screen potential therapeutic drugs.

Results

FCICC and FC-organoid models showed that cancer cells promoted the activation of fibroblasts into CAFs, that CAFs enhanced the invasion of cancer cells, and that CCCT was somewhat heterogeneous. The CCRGPI was developed based on 4 gene pairs: IGF1-IGF1R, LGALS9-CD44, SEMA5A-PLXNA1, and TNXB-SDC1. Furthermore, a high CCRGPI score was identified as an adverse prognostic factor for overall survival (OS). Additionally, a high CCRGPI was positively correlated with the activation of the P53 pathway, a high TP53 mutation rate, and decreased benefit from ICI therapy but was inversely associated with the abundance of various immune cells, such as CD4+ T cells, CD8+ T cells, and B cells. Moreover, Ganetespib was identified as a potential drug for HNSCC combination therapy.

Conclusions

The CCRGPI is reliable for predicting the prognosis and immunotherapy response of HSNCC patients and may be useful for guiding the individualized treatment of HNSCC patients.
Dual targeting non-overlapping epitopes in HER2 domain IV substantially enhanced HER2/HER2 homodimers and HER2/EGFR heterodimers internalization leading to potent antitumor activity in HER2-positive human gastric cancer
Authors: Wei Ruicheng , Zhang Wenli , Yang Futang , Li Qianhao , Wang Qingyu , Liu Ningshu , Zhu Jun , Shan Yongqiang
Published: July 2024

Background

Trastuzumab and pertuzumab combination has been approved for the treatment of patients with HER2-positive metastatic breast cancer. However, trastuzumab and pertuzumab combination did not show improvement in overall survival in patients with HER2-positive metastatic gastric cancer.

Methods

We developed a new HER2-targeted monoclonal antibody, HLX22, targeting HER2 subdomain IV as trastuzumab but with non-overlapping epitopes. We examined the antitumor effects of this novel HER2-antibody in gastric cell lines and cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.

Results

HLX22 in combination with HLX02 (trastuzumab biosimilar) induced enhancement of HER2/HER2 homodimers and HER2/EGFR heterodimers internalization, which ultimately led to the reduction in signal transductions involving STAT3, P70 S6, and AKT; gene expressions of FGF-FGFR-PI3K-MTOR, EGF-EGFR-RAS, TGF-β-SMAD, PLCG and cell cycle progression related pathways that favor tumor development, proliferation, progression, migration and survival in gastric cancer cell line NCI-N87 were also reduced. These differing but complementary actions contributed to the synergistic antitumor efficacy of the HLX22 and HLX02 combination in gastric cancer cell lines, CDX and PDX. In addition, HLX22 in combination with HLX02 demonstrated stronger antitumor efficacy than HLX02 and HLX11 (a potential pertuzumab biosimilar) combination treatment both in vitro and in vivo.

Conclusions

These results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.
High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases
Authors: Zeng Yimo , Ding Hongke , Wang Xingwang , Huang Yanlin , Liu Ling , Du Li , Lu Jian , Wu Jing , Zeng Yukun , Mai Mingqin , Zhu Juan , Yu Lihua , He Wei , Guo Fangfang , Peng Haishan , Yao Cuize , Qi Yiming , Liu Yuan , Li Fake , Yang Jiexia , Hu Rong , Liang Jie , Wang Jicheng , Wang Wei , Zhang Yan , Yin Aihua
Published: July 2024

Background

Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis.

Methods

We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation.

Results

Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications.

Conclusion

CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.
Microsecretory adenocarcinoma of the hard palate: a case report and literature review
Authors: Lu Yin , Wen Yanlin , Feng Sha , Huang Wenting
Published: July 2024

Microsecretory adenocarcinoma (MSA) is a new type of salivary gland neoplasm identified in the 2022 World Health Organization Classification of Head and Neck Tumour (Skalova et al., Head Neck Pathol 16:40-53, 2022) and is characterized by a unique set of histomorphologic and immunohistochemical features and a recurrent MEF2C::SS18 fusion. MSA was initially misdiagnosed as another salivary gland tumour due to its similar morphology; until recently, only fewer than 50 cases were reported. We present a case of MSA of the hard palate with diverse architectural growth patterns, bland cytological features, abundant basophilic intraluminal secretions and fibromyxoid stroma. The tumour cells were positive for the SOX10, S100, and p63 protein and negative for the p40 protein according to immunohistochemistry. SS18 gene rearrangement was demonstrated via break-apart fluorescence in situ hybridization. We also provided a comprehensive literature review and integrated the clinicopathological features, immunophenotype, and molecular alterations of the disease. A comprehensive understanding of MSA enables us to accurately distinguish and categorize MSA from other salivary gland tumours with analogous morphologies.
SP1 regulates BMSC osteogenic differentiation through the miR-133a-3p/MAPK3 axis
Authors: Zhong Liying , Sun Yehai , Wang Cong , Liu Runzhi , Ru Wenjuan , Dai Wei , Xiong Ting , Zhong Aimin , Li Shundong
Published: July 2024

Background

The progression of osteoporosis (OP) can dramatically increase the risk of fractures, which seriously disturb the life of elderly individuals. Specific protein 1 (SP1) is involved in OP progression. However, the mechanism by which SP1 regulates OP progression remains unclear.

Objective

This study investigated the mechanism underlying the function of SP1 in OP.

Methods

SAMP6 mice were used to establish an in vivo model of age-dependent OP, and BALB/c mice were used as controls. BMSCs were extracted from two subtypes of mice. Hematoxylin and eosin staining were performed to mark the intramedullary trabecular bone structure to evaluate histological changes. ChIP assay was used to assess the targeted regulation between SP1 and miR-133a-3p. The binding sites between MAPK3 and miR-133a-3p were verified using a dual-luciferase reporter assay. The mRNA levels of miR-133a-3p and MAPK3 were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The protein expression of SP1, MAPK3, Colla1, OCN, and Runx2 was examined using Western blotting. Alkaline phosphatase (ALP) kit and Alizarin Red S staining were used to investigate ALP activity and mineralized nodules, respectively.

Results

The levels of SP1 and miR-133a-3p were upregulated, whereas the expression of MAPK3 was downregulated in BMSCs from SAMP6 mice, and miR-133a-3p inhibitor accelerated osteogenic differentiation in BMSCs. SP1 directly targeted miR-133a-3p, and MAPK3 was the downstream mRNA of miR-133a-3p. Mechanically, SP1 accelerated osteogenic differentiation in BMSCs via transcriptional mediation of the miR-133a-3p/MAPK3 axis.

Conclusion

SP1 regulates osteogenic differentiation by mediating the miR-133a-3p/MAPK3 axis, which would shed new light on strategies for treating senile OP.
Efficacy and safety of D-penicillamine, trientine, and zinc in pediatric Wilson disease patients
Authors: Lee Eun Joo , Woo Min Hyung , Moon Jin Soo , Ko Jae Sung
Published: July 2024

Objectives

Wilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract’s copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood.

Methods

Ninety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan–Meier analysis.

Results

The median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p < 0.05). Regarding drug changes due to adverse effects, the rate was the highest for DPA, followed by zinc and trientine. There were significant differences between DPA and zinc, zinc and trientine (all p < 0.05), but no significant difference was observed between DPA and zinc (p = 0.22).

Conclusions

In pediatric WD, DPA, zinc, and trientine have therapeutic effects in that order. However, DPA and zinc are associated with more adverse effects compared to trientine.
Ubiquitin recruiting chimera: more than just a PROTAC
Authors: Grigoreva Tatyana A. , Novikova Daria S. , Melino Gerry , Barlev Nick A. , Tribulovich Vyacheslav G.
Published: July 2024

Ubiquitinylation of protein substrates results in various but distinct biological consequences, among which ubiquitin-mediated degradation is most well studied for its therapeutic application. Accordingly, artificially targeted ubiquitin-dependent degradation of various proteins has evolved into the therapeutically relevant PROTAC technology. This tethered ubiquitinylation of various targets coupled with a broad assortment of modifying E3 ubiquitin ligases has been made possible by rational design of bi-specific chimeric molecules that bring these proteins in proximity. However, forced ubiquitinylation inflicted by the binary warheads of a chimeric PROTAC molecule should not necessarily result in protein degradation but can be used to modulate other cellular functions. In this respect it should be noted that the ubiquitinylation of a diverse set of proteins is known to control their transport, transcriptional activity, and protein-protein interactions. This review provides examples of potential PROTAC usage based on non-degradable ubiquitinylation.
Description of Babesia galileei sp. nov. A piroplasmid species causing severe disease in domestic cats
Authors: Baneth Gad , Nachum-Biala Yaarit , Dvorkin Ann , Arogeti Irit , Amiel Shlomo , Soueid Yamit , Shwartz Dor , Mumcuoglu Kosta Y. , Salant Harold
Published: July 2024

Background

Babesiosis is a tick-borne infection caused by piroplasmid protozoa and associated with anemia and severe disease in humans, domestic animals and wildlife. Domestic cats are infected by at least sixBabesiaspp. that cause clinical disease.

Methods

Infection with a piroplasmid species was detected by microscopy of stained blood smears in three sick cats from Israel. Genetic characterization of the piroplasmid was performed by PCR amplification of the18S rRNA, cytochorme B (CytB) and heat shock protein 70 (HSP70) genes and the internal transcribed spacer (ITS) locus, DNA sequencing and phylogenetic analysis. In addition,Haemaphysalis adleriticks collected from two cats were analyzed by PCR for piroplasmids.

Results

The infected cats presented with anemia and thrombocytopenia (3/3), fever (2/3) and icterus (1/3). Comparison of gene and loci sequences found 99–100% identity between sequences amplified from different cats and ticks. Constructed phylogenetic trees and DNA sequence comparisons demonstrated a previously undescribedBabesiasp. belonging to theBabesiasensu stricto (clade X). The piroplasm forms detected included pear-shaped merozoite and round-to-oval trophozoite stages with average sizes larger than those ofBabesia felis,B. leoandB. lengauand smaller than canineBabesias.s. spp. Four of 11H. adleriadult ticks analyzed from cat # 3 were PCR positive forBabesiasp. with a DNA sequence identical to that found in the cats. Of these, two ticks were PCR positive in their salivary glands, suggesting that the parasite reached these glands and could possibly be transmitted byH. adleri.

Conclusions

This study describes genetic and morphological findings of a newBabesiasp. which we propose to nameBabesia galileeisp. nov. after the Galilee region in northern Israel where two of the infected cats originated from. The salivary gland PCR suggests that thisBabesiasp. may be transmitted byH. adleri. However, incriminating this tick sp. as the vector ofB. galileesp. nov. would require further studies.

Graphical Abstract