bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of peer health education intervention on HIV/AIDS knowledge amongst in-school adolescents in secondary schools in Imo State, Nigeria
Authors: Ezelote Chinelo Judith , Osuoji Nkechi Joy , Mbachu Adaku Joy , Odinaka Chikadibia Kizito , Okwuosa Ogochukwu Mildred , Oli Chinaemelum Juliet , Ignatius Chimburuoma Georgina
Published: April 2024

Background

Peer education is an approach to health promotion in which community members are supported to promote health-enhancing change among their peers. The study assessed the effect of peer health education on HIV/AIDS knowledge amongst in-school adolescents in secondary schools in Imo State.

Methods

This was an intervention study carried out among 296 and 287 in-school adolescents aged 15 to 19 years attending Akwakuma Girls Secondary School and Federal Government Girls College Owerri Imo State respectively. The study was in three stages: before intervention, intervention, and after intervention. The impact of peer education was evaluated twelve weeks after intervention. Data were collected using semi-structured questionnaires. The study utilized a quasi-experimental study design. The chi-square test and McNemar’s test were used to test the hypothesis with a significance level of p ≤ 0.05.

Results

The result from the study revealed that the majority (73%) of the respondents at Akwakuma Girls Secondary School (test group) had poor knowledge of HIV/AIDS mode of transmission and prevention at baseline. The overall good knowledge of respondents in the test group improved from 27 to 81% after the intervention. 36% of the respondents in the control group had good knowledge at baseline, the knowledge of 64% of them with poor knowledge at baseline were compared post-test to those in the test group who also had poor knowledge at baseline. The knowledge of only 27.7% of those in the control group increased post-test while the remaining 72.3% still had poor knowledge. The result of the inter-school comparison using Chi-square revealed that the p-value was statistically significant. Intra-school comparison using McNemar’s test revealed a statistical significance for all questions in the test group, while none was positively significant in the control group.

Conclusions

Peer health education improved the knowledge of the students at Akwakuma Girls Secondary School which was very low at the baseline. The knowledge of the students in the control group with poor knowledge at baseline didn’t increase post-study. Peer health education should be strengthened and expanded as one of the tools for behavior change among adolescents. There should be more focus on adolescents for HIV-targeted prevention.
Own price elasticities of the demand for sugar-sweetened beverages in Bangladesh
Authors: Huque Rumana , Azad Abul Kalam , Ahmed Nasiruddin
Published: April 2024

Background

Consumption of sugar-sweetened beverages (SSB) is a major global public health problem. Increasing the price of SSBs through taxation is an effective tool to reduce SSB consumption. Price-elasticity estimates are useful in measuring the effect of taxation on consumption. We estimated the own price elasticities of demand for SSBs in Bangladesh, which will inform how SSB taxes could affect behaviour.

Methods

We used Household Income and Expenditure Survey (HIES) 2016 data, which is a nationally representative dataset at the household level across the country and is conducted using stratified random sampling method. Deaton’s method was used to estimate the price elasticities for SSBs in Bangladesh.

Results

We found that the own price elasticity for SSBs varied between − 0.53% to -1.17% by types of SSBs in Bangladesh. The price elasticity for soft drinks was − 1.17, indicating that if the price of soft drinks increases by 10% via taxes, the quantity consumed of these beverages would reduce by 11.7%.

Conclusion

This is the first study that estimates the own price elasticities of demand for SSBs in Bangladesh. Our results suggest to raise SSB prices through increased taxation in order to reduce SSB consumption and ensure public health gains in Bangladesh.
Impact of immune checkpoint inhibitors (ICIs) therapy on interferon-γ release assay (IGRA) and diagnostic value in non-small cell lung cancer (NSCLC) patients
Authors: Xu Yijiao , Zhang Qingwei , Chen Zhisheng , Yang Shuwen , Chen Haiyan , Xiao Xiong , Jiang Hongni
Published: April 2024

Background

Tuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination.

Methods

A retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis.

Results

A total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis.

Conclusions

For NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT’s diagnostic utility in this context.
FTH1 protects against osteoarthritis by MAPK pathway inhibition of extracellular matrix degradation
Authors: Yuan Zhikun , Yang Lingfeng , Li Yanhui , Li Xuming , Peng Changgui , Pan Jianying , Cai Daozhang
Published: April 2024

Objective

Ferritin heavy chain 1 (FTH1) is an important subunit of ferro-storing proteins and is indispensable for iron metabolism. Though it has been extensively studied in numerous organs and diseases, the relationship between FTH1 and osteoarthritis (OA) is unclear.

Design

Primary murine chondrocytes and cartilage explants were treated with FTH1 siRNA for 72 h. Mice were injected with adenovirus expressing FTH1 after destabilized medial meniscus (DMM) surgery. These approaches were used to determine the effect of FTH1 expression on the pathophysiology of OA.

Results

FTH1 expression was down regulated in OA patients and mice after DMM surgery. Knock down of FTH1 induced articular cartilage damage and extracellular matrix degradation in cartilage explants. Further, over expression of FTH1 reduced the susceptibility of chondrocytes to ferroptosis and reversed decrements in SOX9 and aggrecan after DMM surgery. Moreover, FTH1 relieved OA by inhibition of the chondrocyte MAPK pathway.

Conclusion

This study found FTH1 to play an essential role in extracellular matrix degradation, ferroptosis, and chondrocytes senescence during OA progression. Further, injection of adenovirus expressing FTH1 may be a potential strategy for OA prevention and therapy.
Temporal and geographical variations in diagnostic imaging in Norway
Authors: Hofmann Bjørn Morten , Brandsaeter Ingrid Øfsti , Andersen Eivind Richter , Porthun Jan , Kjelle Elin
Published: April 2024

Background

Unwarranted temporal and geographical variations are acknowledged as a profound problem for equal access and justice in the provision of health services. Even more, they challenge the quality, safety, and efficiency of such services. This is highly relevant for imaging services.

Objective

To analyse the temporal and geographical variation in the number of diagnostic images in Norway from 2013 to 2021.

Methods

Data on outpatient imaging provided by the Norwegian Health Economics Administration (HELFO) and inpatient data afforded by fourteen hospital trusts and hospitals in Norway. Data include the total number of imaging examinations according to the Norwegian Classification of Radiological Procedures (NCRP). Analyses were performed with descriptive statistics.

Results

More than 37 million examinations were performed in Norway during 2013–2021 giving an average of 4.2 million examinations per year. In 2021 there was performed and average of 0.8 examinations per person and 2.2 examinations per person for the age group > 80. There was a 9% increase in the total number of examinations from 2013 to 2015 and a small and stable decrease of 0.5% per year from 2015 to 2021 (with the exception of 2020 due to the pandemic). On average 71% of all examinations were outpatient examinations and 32% were conducted at private imaging centres. There were substantial variations between the health regions, with Region South-East having 53.1% more examinations per inhabitant than Region West. The geographical variation was even more outspoken when comparing catchment areas, where Oslo University Hospital Trust had twice as many examinations per inhabitant than Finnmark Hospital Trust.

Conclusion

As the population in Norway is homogeneous it is difficult to attribute the variations to socio-economic or demographic factors. Unwarranted and supply-sensitive variations are challenging for healthcare systems where equal access and justice traditionally are core values.
A network of transcription factors in complex with a regulating cell cycle cyclin orchestrates fungal oxidative stress responses
Authors: Kan Yanze , He Zhangjiang , Keyhani Nemat O. , Li Ning , Huang Shuaishuai , Zhao Xin , Liu Pengfei , Zeng Fanqin , Li Min , Luo Zhibing , Zhang Yongjun
Published: April 2024

Background

Response to oxidative stress is universal in almost all organisms and the mitochondrial membrane protein, BbOhmm, negatively affects oxidative stress responses and virulence in the insect fungal pathogen, Beauveria bassiana. Nothing further, however, is known concerning how BbOhmm and this phenomenon is regulated.

Results

Three oxidative stress response regulating Zn2Cys6 transcription factors (BbOsrR1, 2, and 3) were identified and verified via chromatin immunoprecipitation (ChIP)-qPCR analysis as binding to the BbOhmm promoter region, with BbOsrR2 showing the strongest binding. Targeted gene knockout of BbOsrR1 or BbOsrR3 led to decreased BbOhmm expression and consequently increased tolerances to free radical generating compounds (H2O2 and menadione), whereas the ΔBbOsrR2 strain showed increased BbOhmm expression with concomitant decreased tolerances to these compounds. RNA and ChIP sequencing analysis revealed that BbOsrR1 directly regulated a wide range of antioxidation and transcription-associated genes, negatively affecting the expression of the BbClp1 cyclin and BbOsrR2. BbClp1 was shown to localize to the cell nucleus and negatively mediate oxidative stress responses. BbOsrR2 and BbOsrR3 were shown to feed into the Fus3-MAPK pathway in addition to regulating antioxidation and detoxification genes. Binding motifs for the three transcription factors were found to partially overlap in the promoter region of BbOhmm and other target genes. Whereas BbOsrR1 appeared to function independently, co-immunoprecipitation revealed complex formation between BbClp1, BbOsrR2, and BbOsrR3, with BbClp1 partially regulating BbOsrR2 phosphorylation.

Conclusions

These findings reveal a regulatory network mediated by BbOsrR1 and the formation of a BbClp1-BbOsrR2-BbOsrR3 complex that orchestrates fungal oxidative stress responses.
Green ecofriendly enhancement of cellulase productivity using agricultural wastes by Aspergillus terreus MN901491: statistical designs and detergent ability on cotton fabrics
Authors: Abdella Mohamed A.A. , Ahmed Nehad E. , Hasanin Mohamed S.
Published: April 2024

Background

Cellulase is considered a group member of the hydrolytic enzymes, responsible for catalyzing the hydrolysis of cellulose and has various industrial applications. Agricultural wastes are used as an inexpensive source for several utilizable products throughout the world. So, searching for cellulase enzymes from fungal strains capable of utilizing agricultural wastes to increase productivity, reduce costs and overcome waste accumulation in the environment is very important to evaluate its potency as a bio-additive to detergent agents.

Results

In the current study, the previously identified fungal strain Aspergillus terreus MN901491 was screened and selected for cellulase production. Medium parameters were optimized using one-factor-at-a-time (OFAT) and multi-factorial (Plackett-Burman and Box-Behnken) design methods. OFAT showed the ability of the fungal strain to utilize agricultural wastes (corn cob and rice straw) as a substrate. Also, yeast extract was the best nitrogen source for enhancing cellulase productivity. The most significant variables were determined by Plackett-Burman Design (PBD) and their concentrations were optimized by Response Surface Methodology (RSM) using Box-Behnken Design (BBD). Among eleven independent variables screened by PBD, malt extract, (NH4)2SO4, and KCl were the most significant ones followed by rice straw which affected cellulase production positively. The ANOVA results particularly the R2-value of PBD (0.9879) and BBD (0.9883) confirmed the model efficiency and provided a good interpretation of the experiments. PBD and BBD improved cellulase productivity by 6.1-fold greater than that obtained from OFAT. Medium optimization using OFAT and statistical models increased cellulase production from A. terreus MN901491 by 9.3-fold compared to the non-optimized medium. Moreover, the efficiency of cellulase activity on cotton fabrics as a bio-additive detergent was evaluated and estimated using whiteness and scanning electron microscope (SEM) that affirmed its potential effect and remarkable detergent ability to improve whiteness by 200% in comparison with non-washed fabric and by 190% in comparison with fabric washed by water.

Conclusion

The presented work was stabilized as a multi-efficiency in which wastes were used to produce cellulase enzyme from the fungal strain, Aspergillus terreus MN901491 as a bio-additive to detergent applications that involved ecofriendly and green processes.
Rural–urban inequalities in health care utilization in Bhutan: a decomposition analysis
Authors: Sharma Jayendra , Pavlova Milena , Groot Wim
Published: April 2024

Background and objective

On the trajectory towards universal health coverage in Bhutan, health equity requires policy attention as significant disparities exist between urban and rural health outcomes. This paper examines health services utilization patterns, inequalities and their socio-economic determinants in rural and urban areas and decomposes the factors behind these differences.

Methods

We used the Bhutan Living Standard Survey 2017 to profile health services utilization patterns and equalities. We employed two different decomposition analyses: decomposition of mean differences in utilization using the Oaxaca–Blinder decomposition framework and differences in the income-related distribution in utilization using recentered influence function regressions between rural and urban areas.

Results

Significant differences exist in the type of outpatient services used by the rural and urban population groups, with those living in rural areas having 3.4 times higher odds of using primary health centers compared to outpatient hospital care. We find that the use of primary health care is pro-poor and that outpatient hospital resources is concentrated among the more affluent section of the population, with this observed inequality consistent across settings but more severe in rural areas. The rural–urban gap in utilization is primarily driven by income and residence in the eastern region, while income-related inequality in utilization is influenced, aside from income, by residence in the central region, household size, and marriage and employment status of the household head. We do not find evidence of significant mean differences in overall utilization or inequality in utilization of inpatient health care services.

Conclusions

While the differences in average contacts with health services are insignificant, there are prominent differences in the level of services availed and the associated inequality among rural and urban settings in Bhutan. Besides, while there are obvious overlaps, factors influencing income-related inequality are not necessarily the same as those driving the utilization gaps. Cognizance of these differences may lead to better informed, targeted, and potentially more effective future research and policies for universal health coverage.
Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress
Authors: Liu Ruiyuan , Zhang Tianlu , Bai Chaobo , Chen Jing , Zhang Xin , Liu Guiying , Shen Songjie , Yuan Junliang , Lu Zhiguo
Published: April 2024

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.
Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer
Authors: Lan Zhou , Liu Wei-Jia , Yin Wu-Wei , Yang Sheng-Ren , Cui Hao , Zou Ke-Long , Cheng Guo-Wang , Chen Hao , Han Yan-Hua , Rao Lang , Tian Rui , Li Ling-Ling , Zhao Yu-Yue , Yu Guang-Tao
Published: April 2024

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+T cells as well as CD103+DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.
Finely tuned ionizable lipid nanoparticles for CRISPR/Cas9 ribonucleoprotein delivery and gene editing
Authors: Im San Hae , Jang Mincheol , Park Ji-Ho , Chung Hyun Jung
Published: April 2024

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.
Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles
Authors: Liu Xixi , Shen Lu , Wan Meidan , Xie Hui , Wang Zhenxing
Published: April 2024

Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies.

Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: “neurodegenerative disease” OR “Alzheimer’s disease” OR “Parkinson’s disease” OR “Amyotrophic lateral sclerosis” AND “extracellular vesicles” OR “exosomes” OR “outer membrane vesicles” AND “drug delivery systems” AND “blood-brain barrier”. MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.
Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer
Authors: Zeng Daolin , Yu Chunlin , Chen Shiyao , Zou Long , Chen Junjun , Xu Linlong
Published: April 2024

Objective

The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE).

Methods

92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments.

Results

the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05).

Conclusion

SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.
Development of nanobodies targeting hepatocellular carcinoma and application of nanobody-based CAR-T technology
Authors: Lin Keming , Xia Baijin , Wang Xuemei , He Xin , Zhou Mo , Lin Yingtong , Qiao Yidan , Li Rong , Chen Qier , Li Yuzhuang , Feng Jinzhu , Chen Tao , Chen Cancan , Li Xinyu , Zhang Hui , Lu Lijuan , Liu Bingfeng , Zhang Xu
Published: April 2024

Background

Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative.

Methods

In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation.

Results

Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo.

Conclusions

In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.
Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk
Authors: Fan Junjie , Liu Li , Lu Yongling , Chen Qian , Fan Shijun , Yang Yongjun , Long Yupeng , Liu Xin
Published: April 2024

Background

The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized.

Results

In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection.

Conclusion

Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.
Cryopreservation of sessile oak (Quercus petraea (Matt.) Liebl.) plumules using aluminium cryo-plates: influence of cryoprotection and drying
Authors: Wasileńczyk Urszula , Wawrzyniak Mikołaj Krzysztof , Martins João Paulo Rodrigues , Kosek Paulina , Chmielarz Paweł
Published: April 2024

Background Quercus

seeds that are recalcitrant to desiccation and freezing temperatures cannot be stored in gene banks under conventional conditions. However, the germplasm of some recalcitrant seeded species can be stored in liquid nitrogen (–196 °C). Unfortunately, for many species, among them for almost the whole genus Quercus, an effective cryostorage method is still unknown. In this study, we propose a successful cryostorage protocol for Quercus petraea (Matt.) Liebl. germplasm using plumules (a shoot apical meristem of an embryo) frozen on aluminium cryo-plates.

Results

The plumules isolated from the acorns of ten provenances were prestored in 0.5 M sucrose solution (for 18 h). To form alginate beads (one plumule per bead), the plumules were placed in the wells of a cryo-plate and embedded in calcium alginate gel. For cryoprotection, the encapsulated plumules were immersed in cryoprotectant solution containing 2.0 M glycerol and different concentrations of sucrose (0.8–1.2 M) for 40 min at 25 °C and desiccated under a laminar flow cabinet for 1.0–4.0 h. Cryo-plates with plumules were directly immersed in liquid nitrogen and then cryostored for 30 min. For rewarming, cryo-plates with plumules were immersed in 1.0 M sucrose solution and rehydrated for 15 min at 25 °C. Survival rates varied from 25.8 to 83.4 were achieved after cryoprotection in 1.0 M sucrose solution and the drying of plumules for 2 h. The in vitro regrowth rate of cryopreserved plumules varied among provenances and was 26–77%.

Conclusions

This study presents, for the first time, a successful, simple and effective protocol for the cryopreservation of Q. petraea germplasm that could be used in gene banks. The experiment was successfully repeated on seeds from various provenances, each yielding similar, good results. However, seed quality and storage time after harvesting are important factors in plumule regrowth after cryopreservation.
Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series
Authors: Andrási Terézia B. , Abudureheman Nunijiati , Glück Alannah C. , Dielmann Kai , Dinges Gerhard
Published: April 2024

Background

The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure.

Case summary

Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free.

Discussion

Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.
Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment
Authors: Yee Karen S. , Alexanderian David , Martin Susan , Olayinka-Amao Bimpe , Whiteman David A. H.
Published: April 2024

Background

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials.

Results

This qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had anIDSvariant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with largeIDSdeletions; 67% of these patients were rated as improved/improving or stabilized disease.

Conclusions

This qualitative analysis provides a snapshot of clinicians’ considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.
Clinical and genetic study of ABCB4 gene-related cholestatic liver disease in China: children and adults
Authors: Cao Lili , Ling Xiuxin , Yan Jianguo , Feng Danni , Dong Yi , Xu Zhiqiang , Wang Fuchuan , Zhu Shishu , Gao Yinjie , Cao Zhenhua , Zhang Min
Published: April 2024

Background

ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. The correlation between genotype and clinical phenotype still unclear. This study retrospectively analyzed the clinical and pathological characteristics of 23 patients with ABCB4 gene-related cholestatic liver diseases. Next-generation sequencing was used to identify the genetic causes.

Results

The 23 included patients (15 children and 8 adults) were diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3), drug-induced liver injury (DILI), cirrhosis cholestasis, cirrhosis, and mild liver fibrosis. Nineteen patients underwent liver pathological examination of the liver, exhibiting fibrosis, small bile duct hyperplasia, CK7(+), Cu(+), bile duct deletion, and cirrhosis. Thirty ABCB4 variants were identified, including 18 novel variants.

Conclusion

ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. Biallelic ABCB4 mutation carriers tended to severe PFIC3, which mostly occurs in children; while ABCB4 non-biallelic variants can lead to milder ICP, LACP, DILI or overlapping, mostly in adults. Thus, the ABCB4 genotype has a specific correlation with the phenotype, but there are exceptions. Non-biallelic null mutations can cause severe diseases. The mechanisms underlying this genetic phenotype require further investigation.

Graphical Abstract
Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer
Authors: Zhang Ningning , Huang Yuxin , Wang Guanwen , Xiang Yimei , Jing Zhouhong , Zeng Junjie , Yu Feng , Pan Xianjun , Zhou Wenqi , Zeng Xiaohua
Published: April 2024

Background

This study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients.

Methods

A total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines.

Results

Twenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels.

Conclusion

Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.
Parietal abdominal pain with lower leg discrepancy: a case report
Authors: Gritli Agnès , Ramirez David Cadavid , Decavel Pierre
Published: April 2024

Background

This report involves the first publication describing a case of parietal abdominal pain due to lower limb length discrepancy.

Case presentation

A Caucasian male patient in his 50s was referred to our rehabilitation department with chronic abdominal pain that began in childhood. This chronic pain was associated with episodes of acute pain that were partially relieved by grade 3 analgesics. The patient was unable to sit for long periods, had recently lost his job, and was unable to participate in recreational activities with his children. Investigations revealed contracture and hypertrophy of the external oblique muscle and an limb length discrepancy of 3.8 cm (1.5 inches) in the left lower limb. The patient was effectively treated with a heel raise, physiotherapy, intramuscular injection of botulinum toxin, and lidocaine. The patient achieved the therapeutic goals of returning to work, and reducing analgesic use.

Conclusions

Structural misbalances, as may be caused by lower leg discrepancy, may trigger muscular compensations and pain. Complete anamnesis and clinical examination must not be trivialized and may reveal previously ignored information leading to a proper diagnosis.
Does arthroscopic or open washout in native knee septic arthritis result in superior post-operative function? A systematic review and meta-analysis of randomised controlled trials and observational studies
Authors: Kennedy Grace E. M. , Tharmaseelan Abisha , Phillips Jonathan R. A. , Evans Jon T. , Kunutsor Setor K.
Published: April 2024

Aims

Septic arthritis (SA) of the native knee joint is associated with significant morbidity. This review compared post-operative functional outcomes (patient-reported outcome measures (PROMs) and range of movement (ROM)) following arthroscopic washout (AW) and open washout (OW) amongst adult patients with SA of the native knee. The need for further operative intervention was also considered.

Methods

Electronic databases of PubMed, MEDLINE, Embase, Cochrane, Web of Science and Scopus were searched between 16 February 2023 and 18 March 2023. Randomised controlled trials (RCTs) and comparative observational analytic studies comparing function (reflected in PROMs or ROM) at latest follow-up following AW and OW were included. A narrative summary was provided concerning post-operative PROMs. Pooled estimates for mean ROM and re-operation rates were conducted using the random-effects model. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool-2 for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions tool for observational analytic studies.

Results

Of 2580 retrieved citations, 7 articles (1 RCT and 6 cohort studies) met the inclusion criteria. Of these, five had some concerns/moderate risk of bias, and two had serious risk. There was a slight tendency for superior mean PROMs following AW compared with OW, but due to small effect sizes, this was unlikely clinically relevant. Additionally, the use of four different PROMs scales made direct comparisons impossible. AW was associated with superior ROM (mean difference 20.18° (95% CI 14.35, 26.02; p < 0.00001)), whilst there was a tendency for lower re-operation requirements following AW (OR 0.64, 95% CI 0.26, 1.57, p = 0.44).

Conclusions

AW was associated with equivalent to superior post-operative function and lower requirement for further intervention compared with OW. Results need to be interpreted cautiously, taking into consideration the methodological and clinical heterogeneity of the included studies.

Systematic review registration

PROSPERO 2022, CRD42022364062.