bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation
Authors: Jiang Yunzhong , Zhang Mengzhao , Wang Lu , Zhang Lu , Ma Minghai , Jing Minxuan , Li Jianpeng , Song Rundong , Zhang Yuanquan , Yang Zezhong , Zhang Yaodong , Pu Yuanchun , Qu Xiaowei , Fan Jinhai
Published: April 2023

Background

Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer.

Methods

Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein–protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole.

Results

Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways.

Conclusions

We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer.

Subjects

Bioinformatics, Computational Biology, Molecular Biology.
Nigella sativa powder for helicobacter pylori infected patients: a randomized, double-blinded, placebo-controlled clinical trial
Authors: Yousefnejad Hedieh , Mohammadi Farzaneh , Alizadeh-naini Mahvash , Hejazi Najmeh
Published: April 2023

Objective

This double-blind, placebo-controlled, clinical trial was conducted to define the effects of Nigella sativa (N. Sativa) powder plus conventional medical treatment ofHelicobacter pylori(H. pylori) on serum ghrelin level and appetite inH. pylori-infected patients.

Methods

In the present study, 51H. pylori-positive patients were randomly allocated to treatment (n = 26) or placebo (n = 25) groups. They received 2 g/dayN. Sativawith quadruple therapy or 2 g/day placebo plus quadruple therapy for 8 weeks. The serum level of ghrelin was assessed before and after the intervention. Appetite was evaluated at the onset and at the end of the intervention.

Results

At the end of the study, the appetite of the treatment group improved significantly compared with the placebo group (P = 0.02). Statistically, the difference in serum ghrelin levels between the study’s groups was insignificant (P > 0.05).

Conclusion

Supplementation withN. Sativapowder may be a beneficial adjunctive therapy inH. pylori-infected patients.

Trial registration

This study was registered in the Iranian Registry of Clinical Trials (IRCT20170916036204N7) on 08/08/2018.
Development and evaluation of an online surgical elective for medical students
Authors: Goble Mary , Chapman Neil
Published: April 2023

Background

Decreased experiential learning opportunities exacerbated by the COVID-19 pandemic have increased development of online surgical educational courses. To what extent may such courses provide exposure to broad and accessible surgical education?

Methods

Surge is a 6-week online surgical elective hosted within a virtual learning environment, covering all surgical specialties. Course content is mapped to the Royal College of Surgeons’ Undergraduate Curriculum in Surgery. Each week consultant surgeons discuss their specialty in short videos on anatomy, pathology and lifestyle of a surgeon. Students also engage with learning activities; further reading lists; formative quizzes and live sessions including suturing practice. Participants were medical students undertaking third-year electives at the University of Sheffield. Pre- and post-course questionnaires investigated student interest in surgery, understanding of steps required to pursue a surgical career and confidence in surgical environments. Qualitative data was collected via free-text responses and analysed with content analysis. Quantitative data was collected using 5-point Likert scales (1 = Strongly Disagree; 5 = Strongly Agree) and analysed using the Wilcoxon signed-rank test.

Results

Twenty-two students participated in Surge over five 6-week cohorts. Examination of free-text responses revealed students gained increased understanding of available surgical career options. Students felt better informed regarding different surgical specialties (median score 2.5 vs. 4, p = 0.000) and steps required to develop a surgical portfolio (median score 2 vs. 5, p = 0.000). Additionally, confidence in understanding of relevant intraoperative steps improved (median score 3 vs. 4, p = 0.000).

Conclusion

These data demonstrate Surge increased student confidence and understanding of surgical careers despite reduced in-person opportunities to engage with surgical education. Surge will continue to be developed and evaluated on a larger scale.
Using graphic medicine in teaching multicultural nursing: a quasi-experimental study
Authors: Lesińska-Sawicka Małgorzata
Published: April 2023

Background

Comics, as an art form that combines words and images, can be used with great success in teaching nursing students. Teaching content on multicultural issues is not easy, especially since, in addition to knowledge, it is important to pay attention to communication skills, attitudes of respect, openness or empathy, among others. It is difficult to recognize or discuss these attitudes without student involvement. Graphic stories, comic strips provide such opportunities and facilitate learning new content, even those difficult to communicate naturally and spontaneously. The aim of this paper is to present the possibilities of using the graphic method, in particular comics and graphic novels, in teaching nursing, based on the example of multicultural nursing.

Methods

Quasi-experimental intervention study with a quantitative approach, guided by the STROBE tool The survey was conducted March–May 2022 among State University of Applied Sciences in Piła students. First, students’ knowledge of cultural issues was assessed, then they were randomly assigned to two groups. One group had classes using a comic book, and the other group had classes using traditional methods. After the class, the students’ knowledge was assessed again. Descriptive statistical analyses were performed to obtain the mean, median, standard deviation (SD). Data followed a normal distribution. Data was verified by the t-Students test for independent groups.

Results

Respondents’ knowledge on cultural issues before taking the course was satisfactory, with a mean score of 19.1. After completing the course, knowledge on cultural issues increased and was rated as very good and the mean score for all respondents was 26.9. Statistical analysis showed that there was statistical significance between the groups and the number of points achieved in the posttest. Respondents in the intervention group scored higher than those in the comparsion group.

Conclusion

The use of the graphic method, which is one of the forms of active learning, in teaching cultural content to nursing students has positive didactic effects. Students achieve better learning outcomes in terms of knowledge, skills and attitudes in a way that is more engaging. This makes learning difficult topics, such as a cultural issue, more effective.

It would be worth considering using this method for other courses and/or at other universities as well.
The effectiveness of teaching complementary and alternative medicine based on the components of theory of planned behavior on nutrition students: multicenter research study
Authors: Mahmoodi Mohammad Reza , Shafian Sara , Alinaghizade Manizhe Shaban
Published: April 2023

Objective

Safe and beneficial use of complementary and alternative medicine (CAM) modalities results from integrating CAM education into curricula and increasing CAM knowledge. We sought how much teaching CAM procedures in a virtual environment can influence the components of the theory of planned behavior (TPB), including knowledge, attitude, behavioral intention, and behavior of nutrition students.

Methods

This cross-sectional descriptive-analytic study was conducted on 162 undergraduate nutrition students were selected through convenience sampling based on inclusion criteria in 2021–2022. Data were collected through a validated researcher-made CAM questionnaire that was designed based on TPB questionnaire that consisted of four constructs (knowledge, attitude, behavioral intention, and behavior). The content validity index and content validity ratio of the questionnaire were evaluated.

Results

Our results revealed that students who significantly scored the highest scores in attitude, behavioral intention, and behavior constructs were the students who claimed that “teaching two credits of CAM for nutrition students is not enough” (p. value =  < 0.001, < 0.001, and 0.005, respectively). In addition, these students used treatment methods of CAM for themselves, suggested treatment methods of CAM to others, and followed the recommendations of the CAM specialists (for three pairwise comparisons: p. value =  < 0.001, < 0.001, and < 0.001, respectively). The attitude could predict 70% of behavioral intention. However, attitude and behavioral intention could predict 90% of behavior.

Conclusion

Attitude was the most critical determinant influencing behavioral intention and behavior. CAM teaching using evidence-based CAM-ITM principles with a succinct, concerted, and collaborative curriculum, integration of CAM into continuing education, and integration of educational CAM programs continuously for several years into the academic curriculum in the actual setting influence the success of the educational CAM program.
Secretory expression of recombinant small laccase genes in Gram-positive bacteria
Authors: Välimets Silja , Pedetti Patricia , Virginia Ludovika Jessica , Hoang Mai Ngoc , Sauer Michael , Peterbauer Clemens
Published: April 2023

Background

Laccases are multicopper enzymes that oxidize a wide range of aromatic and non-aromatic compounds in the presence of oxygen. The majority of industrially relevant laccases are derived from fungi and are produced in eukaryotic expression systems such asPichia pastorisandSaccharomyces cerevisiae. Bacterial laccases for research purposes are mostly produced intracellularly inEscherichia coli, but secretory expression systems are needed for future applications. Bacterial laccases fromStreptomycesspp. are of interest for potential industrial applications because of their lignin degrading activities.

Results

In this study, we expressed small laccases genes fromStreptomyces coelicolor,Streptomyces viridosporusandAmycolatopsis75iv2 with their native signal sequences in Gram-positiveBacillus subtilisandStreptomyces lividanshost organisms. The extracellular activities ofScLac,SvLac andAmLac expressed inS. lividansreached 1950 ± 99 U/l, 812 ± 57 U/l and 12 ± 1 U/l in the presence of copper supplementation. The secretion of the small laccases was irrespective of the copper supplementation; however, activities upon reconstitution with copper after expression were significantly lower, indicating the importance of copper during laccase production. The production of small laccases inB. subtilisresulted in extracellular activity that was significantly lower than inS. lividans. Unexpectedly,AmLac andScLac were secreted without their native signal sequences inB. subtilis, indicating thatB. subtilissecretes some heterologous proteins via an unknown pathway.

Conclusions

Small laccases fromS. coelicolor,S. viridosporusandAmycolatopsis75iv2 were secreted in both Gram-positive expression hostsB. subtilisandS. lividans, but the extracellular activities were significantly higher in the latter.
Carcinogenic effect of arsenic in digestive cancers: a systematic review
Authors: Kasmi Sophie , Moser Laureline , Gonvers Stéphanie , Dormond Olivier , Demartines Nicolas , Labgaa Ismail
Published: April 2023

Background

The carcinogenic effect of arsenic (As) has been documented in lung, bladder and skin cancers but remains unclear for digestive cancers, although metabolic pathways of As and recent data suggest that it may be an important determinant in these malignancies as well.

Objective

This study aimed to systematically review the available literature investigating the potential association between As and digestive cancers.

Methods

An extensive search was conducted in Medline Ovid SP, Cochrane, PubMed, Embase.com, Cochrane Library Wiley, Web of Science and Google Scholar. Studies providing original data in humans, with As measurement and analysis of association with digestive cancers including esogastric cancers (esophagus and stomach), hepato-pancreatico-biliary (HPB) cancers (including biliary tract, liver and pancreas) and colorectal cancers were eligible.

Results

A total of 35 studies were identified, 17 ecological, 13 case–control and 5 cohort studies. Associations between As and digestive cancers were reported for both risks of incidence and cancer-related mortality. Overall, 43% (3/7) and 48% (10/21) studies highlighted an association between As and the incidence or the mortality of digestive cancers, respectively.

Conclusions

A substantial proportion of studies exploring the potential link between As and digestive cancers suggested an association, particularly in HPB malignancies. These findings emphasize the need to further investigate this topic with dedicated and high-quality studies, as it may have an important impact, including for prevention strategies.
Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis
Authors: Qin Qiaoxi , Zhou Yang , Li Pan , Liu Ying , Deng Ruxi , Tang Rui , Wu Nianhong , Wan Li , Ye Ming , Zhou Hong , Wang Zhiming
Published: April 2023

Background

Magnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 °C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis.

Results

To address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50℃ to approximately 44℃ with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem.

Conclusion

Our work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential.
Health-related quality of life among patients with end-stage renal disease undergoing hemodialysis in Ethiopia: a cross-sectional survey
Authors: Gebrie Mignote Hailu , Asfaw Hussen Mekonnen , Bilchut Workagegnehu Hailu , Lindgren Helena , Wettergren Lena
Published: April 2023

Background

Measurement of health-related quality of life (HRQOL) enables identification of treatment-related side effects of a disease. Such aspects may negatively impact on patients’ lives and should be taken into consideration in medical decision-making. In sub-Saharan Africa, research from the perspective of patients with chronic kidney disease is scarce, and it is almost non-existent in patients undergoing hemodialysis. We aimed to determine HRQOL among end-stage renal disease patients undergoing maintenance hemodialysis in Ethiopia and to identify factors associated with HRQOL.

Methods

A multi-center cross-sectional study was conducted in Addis Ababa, Ethiopia directed to all patients receiving hemodialysis due to kidney failure at 11 randomly-selected government and private hospitals/dialysis centers in the capital of Ethiopia. Data were collected by trained nurses using the KDQOL-36 instrument with five subscales measuring generic and disease-specific HRQOL. Study-specific items were used to collect socio-demographic and clinical data. Factors associated with HRQOL were examined using multivariable linear regression models.

Results

Four hundred eighty-one patients completed the survey through face-to-face interviews (response rate 96%; mean age 45.34 ± 14.67). The mean scores of the subscales ranged from 25.6 to 66.68 (range 0–100), with higher scores reflecting better health. Factors associated with low HRQOL included older age, female sex, no formal education, poor medication adherence, > 2 hemodialysis sessions/week, lower body mass index (< 18.5), longer duration of hemodialysis treatment (≥ 12 months), and poor social support.

Conclusion

Patients with kidney failure undergoing hemodialysis in Addis Ababa, Ethiopia, had low HRQOL across all subscales compared to previous studies. Therefore, the implementation of guidelines is crucial to improve patients’ adherence to their prescribed medications. Furthermore, establishing patient support groups and encouraging patients to use the available support resources from family members, neighbors, and friends have the potential to improve patients’ HRQOL.
Current perspectives on cell-assisted lipotransfer for breast cancer patients after radiotherapy
Authors: Wu Qiuwan , Chen Shuai , Peng Wuyun , Chen Donghan
Published: April 2023

Background

Cell-assisted lipotransfer (CAL), a technique of autologous adipose transplantation enriched with adipose-derived stem cells (ADSCs), has the potential to improve cosmetic outcomes at irradiated sites. However, many concerns have been raised about the possibility of ADSCs increasing oncological risk in cancer patients. With the increasing demand for CAL reconstruction, there is an urgent need to determine whether CAL treatment could compromise oncological safety after radiotherapy, as well as to evaluate its efficacy in guiding clinical decisions.

Methods

A PRISMA-compliant systematic review of the safety and efficacy of CAL in breast cancer patients after radiotherapy was conducted. The PubMed, Ovid, Cochrane Library, and ClinicalTrials.gov databases were comprehensively searched from inception to 31 December 2021.

Results

The search initially yielded 1185 unique studies. Ultimately, seven studies were eligible. Based on the limited outcome evidence, CAL did not increase recurrence risk in breast cancer patients but presented aesthetic improvement and higher volumetric persistence in a long-term follow-up. Although breast reconstruction with CAL also had oncological safety after radiotherapy, these patients needed more adipose tissue and had relatively lower fat graft retention than the non-irradiated patients (P < 0.05).

Conclusions

CAL has oncological safety and does not increase recurrence risk in irradiated patients. Since CAL doubles the amount of adipose required without significantly improving volumetric persistence, clinical decisions for irradiated patients should be made more cautiously to account for the potential costs and aesthetic outcomes. There is limited evidence at present; thus, higher-quality, evidence-based studies are required to establish a consensus on breast reconstruction with CAL after radiotherapy.
Noninvasive ultrasound stimulation to treat myocarditis through splenic neuro-immune regulation
Authors: Liu Tianshu , Fu Yanan , Shi Jiawei , He Shukun , Chen Dandan , Li Wenqu , Chen Yihan , Zhang Li , Lv Qing , Yang Yali , Jin Qiaofeng , Wang Jing , Xie Mingxing
Published: April 2023

Background

The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined.

Methods

The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups.

Results

The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation.

Conclusions

It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.

Graphical Abstract
Application of four-dimensional cone beam computed tomography in lung cancer radiotherapy
Authors: Abulimiti Muyasha , Yang Xu , Li Minghui , Huan Fukui , Zhang Yanxin , Jun Liang
Published: April 2023

Objective

This study explored the application of four-dimensional cone beam computed tomography (4D CBCT) in lung cancer patients, seeking to improve the accuracy of radiotherapy and to establish a uniform protocol for the application of 4D CBCT in radiotherapy for lung cancer.

Methods

4D CBCT was applied to evaluate tumor volume response (TVR), motion, and center coordinates during radiotherapy in 67 eligible individuals with lung cancer diagnoses. The differences between 4D CBCT and 3D CBCT in different registration methods were compared.

Results

TVR was observed during treatment in 41% of patients (28/67), with a mean volume reduction of 41.7% and a median time to TVR of 19 days. Tumor motion was obvious in 16 patients, with a mean value of 0.52 cm (0.22 to 1.34 cm), and in 3 of 6 tumors close to the diaphragm (0.28 to 0.66 cm). Gray value registration based on mean density projection could still achieve close results to the 4D gray value registration. However, when the registration was based on bone alone, partial off-targeting occurred in the treatment in 41.8% of cases. The off-target rate was 19.0% when the tumor motion was ≤ 0.5 cm and 52.2% when the motion was > 0.5 cm.

Conclusion

Tumor volume and motion of intrapulmonary lesions in individuals diagnosed with lung cancer varied significantly in the third week of radiotherapy. 4D CBCT may be more advantageous for isolated lesions without reference to relative anatomical structures or those near the diaphragm. Grayscale registration based on mean density projection is feasible.
Redo mitral surgery after coronary artery bypass grafts under hyperkalemic hypothermia using thoracotomy and axillary artery cannulation in a patient with functioning bilateral internal thoracic arteries and atheromatous aorta
Authors: Suzuki Ryo , Akita Masafumi , Itohara Takaki , Komatsu Takuya
Published: April 2023

Background

Redo mitral valve surgery using resternotomy after coronary artery bypass grafting (CABG) is challenging as previous CABG with patent internal thoracic artery (ITA) poses a risk of injury due to dense adhesion. It is paramount to have alternative method to minimize this risk.

Case presentation

: We report a case of redo mitral and tricuspid valve repair via right thoracotomy under hypothermia and systemic potassium administration with axillary artery cannulation in a patient after CABG with patent bilateral ITA grafts crossing over the sternum. Herein, critical dissection around the aorta and functioning ITA grafts was avoided by performing the procedure under systemic hypothermia via thoracotomy. Furthermore, considering the presence of atheroma in the aorta, the axillary artery was used as a perfusion route to prevent stroke events. Postoperative course was uneventful and echocardiography demonstrated preserved cardiac function.

Conclusion

Performing axillary artery cannulation and right thoracotomy under hypothermic cardiac arrest with systemic hyperkalemia without clamping the patent bilateral ITAs and aorta allowed us to perform redo mitral valve surgery after CABG without major postoperative cardiac or cerebral complications.
Ruptured mycotic aneurysm of intercostal arteries associated with vertebral osteomyelitis: a case report
Authors: Tsukamoto Masatsugu , Morimoto Tadatsugu , Yoshihara Tomohito , Mawatari Masaaki
Published: April 2023

Background

Here, we report a rare case of massive hemothorax caused by rupture of an intercostal artery pseudoaneurysm associated with pyogenic spondylodiscitis, which was successfully treated with endovascular intervention.

Case presentation

A 49-year-old man with schizophrenia, idiopathic esophageal rupture, postoperative mediastinal abscess, and pyothorax, diagnosed with pyogenic spondylodiscitis caused by methicillin-resistant Staphylococcus aureus. Magnetic resonance imaging and computed tomography (CT) showed extensive vertebral body destruction. The patient underwent a two-stage operation: anterior vertebral debridement and fixation with iliac bone graft and 10 days after first surgery, posterior fixation with instrumentation. Seven days after second surgery, the patient’s right chest pain increased, his blood pressure dropped, and he had shock. Chest X-ray showed massive hemothorax in the right lung. Chest CT and subsequent intercostal arteriography showed a pseudoaneurysm in the right T8 intercostal artery and active contrast extravasation from it. This seemed ruptured mycotic aneurysms involving intercostal vessels. These vessels were successfully embolized using micro-coils. Then, the patient completed the prescribed antimicrobial therapy in the hospital without any complications.

Conclusions

Intercostal artery aneurysms are rare vascular abnormalities. They have the risk of rupture and may sometimes cause hemothorax and can be potentially life-threatening. Ruptured intercostal artery pseudoaneurysms are a good indication of endovascular intervention, and prompt embolization saved the life of the patient in this case report. This case report highlights the possibility of a ruptured intercostal mycotic aneurysm in patients with pyogenic spondylodiscitis and reminds physicians to be alert of this rare but potentially fatal complication.
Shengjiang San alleviated sepsis-induced lung injury through its bidirectional regulatory effect
Authors: Yan Shifan , Jiang Yu , Yu Ting , Hou Changmiao , Xiao Wen , Xu Jing , Wen Huili , Wang Jingjing , Li Shutong , Chen Fang , Li Shentang , Liu Xiehong , Tan Hao , Zou Lianhong , Liu Yanjuan , Zhu Yimin
Published: April 2023

Background

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear.

Methods

To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF–MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1.

Results

SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase.

Conclusions

SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect.
How do patients and other members of the public engage with the orphan drug development? A narrative qualitative synthesis
Authors: Frost Julia , Hall Abi , Taylor Emily , Lines Sarah , Mandizha Jessica , Pope Catherine
Published: April 2023

Background

The diversity of patient experiences of orphan drug development has until recently been overlooked, with the existing literature reporting the experience of some patients and not others. The current evidence base (the best available current research) is dominated by quantitative surveys and patient reported outcome measures defined by researchers. Where research that uses qualitative methods of data collection and analysis has been conducted, patient experiences have been studied using content analysis and automatic textual analysis, rather than in-depth qualitative analytical methods. Systematic reviews of patient engagement in orphan drug development have also excluded qualitative studies. The aim of this paper is to review qualitative literature about how patients and other members of the public engage with orphan drug development.

Methods

We conducted a systematic search of qualitative papers describing a range of patient engagement practices and experiences were identified and screened. Included papers were appraised using a validated tool (CASP), supplemented by reporting guidance (COREQ), by two independent researchers.

Results

262 papers were identified. Thirteen papers reported a range of methods of qualitative data collection. Many conflated patient and public involvement and engagement (PPIE) with qualitative research. Patients were typically recruited via their physician or patient organisations. We identified an absence of overarching philosophical or methodological frameworks, limited details of informed consent processes, and an absence of recognisable methods of data analysis. Our narrative synthesis suggests that patients and caregivers need to be involved in all aspects of trial design, including the selection of clinical endpoints that capture a wider range of outcomes, the identification of means to widen access to trial participation, the development of patient facing materials to optimise their decision making, and patients included in the dissemination of trial results.

Conclusions

This narrative qualitative synthesis identified the explicit need for methodological rigour in research with patients with rare diseases (e.g. appropriate and innovative use of qualitative methods or PPIE, rather than their conflation); strenuous efforts to capture the perspectives of under-served, under-researched or seldom listened to communities with experience of rare diseases (e.g. creative recruitment and wider adoption of post-colonial practices); and a re-alignment of the research agenda (e.g. the use of co-design to enable patients to set the agenda, rather than respond to what they are being offered).
Imaging ovarian cancer – from baseline characteristics to high-risk image factors
Authors: Sartor Hanna , Bjurberg Maria , Asp Mihaela , Kahn Anna , Brändstedt Jenny , Kannisto Päivi , Jirström Karin
Published: April 2023

Background

Imaging ovarian cancer (OC) includes evaluating peritoneal carcinomatosis (PC) and enlarged cardio phrenic lymph nodes (CPLN) by computed tomography (CT), and thorough evaluation is tedious work. A “CT short score” with high-risk CT parameters might be a more pragmatic approach, but it is not known if such a short score associates with aggressive OC subtypes and impaired OC survival. Further, it is not known if certain established OC risk factors are linked to high-risk CT-findings which would be important in image evaluation. Herein, we investigate a CT short score and its relation to baseline characteristics, OC subtypes, and survival.

Methods

The Malmö Diet and Cancer Study is a prospective cohort that included 17,035 women (1991–1996). Baseline characteristics and tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. A CT short score (CPLN and PC-index (PCI) in seven regions) was registered and associations with clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed with logistic and Cox regression, respectively. Parity and menopausal status were analyzed in relation to short score and PCI.

Results

There was an association between higher short score and advanced clinical stage (adjusted OR 2.76 (1.42—5.38)), adjusted for age at diagnosis and histological type/grade. Higher short score was associated with impaired OC specific survival (adjusted HR 1.17 (1.01—1.35)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There were no significant associations between parity, menopausal status, and short score/PCI.

Conclusions

CT short score was significantly associated with advanced clinical stages and impaired OC survival. A pragmatic approach (based on CT) to evaluate high risk image findings in OC could help reduce radiologists’ workload and at the same time provide structured reports to surgeons and oncologists involved in OC care.
Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling
Authors: Liu Heshu , Yan Rui , Xiao Zeru , Huang Xuying , Yao Jiannan , Liu Jian , An Guangyu , Ge Yang
Published: April 2023

Triple-negative breast cancer (TNBC) exhibits the poorest outcomes among breast cancer subtypes due to the high heterogeneity and a lasting scarcity of effectual treatments. Targeted therapies based on molecular subtypes of TNBC are critical step toward tailoring treatments to improve clinical outcomes. Gastrointestinal cancer stem cell (CSC) marker DCLK1 was reported to be highly expressed in stem cell-rich subtype of TNBC. Here, we firstly explored the impacts of DCLK1 on tumor cells as well as their immune microenvironment in TNBC and potential therapeutic strategies for TNBC patients with high DCLK1 expression. Our results disclosed that DCLK1 overexpression promoted, while knockout of DCLK1 suppressed the CSC-like traits of TNBC cells and resistance to chemotherapeutics. Besides, DCLK1 supported immune escape by inhibiting intratumoral cytotoxic T cell infiltration in TNBC and hence limited immune checkpoint inhibitors efficacy. Mechanistically, bioinformatics analysis revealed that IL-6/STAT3 signaling was significantly enriched in high DCLK1-expressing patients, and our results further revealed that DCLK1 enhanced IL-6 expression and STAT3 activation in TNBC cells, which finally gave rise to upregulated CSC traits and suppressed CD8+ T-cell activity. Inhibiting IL-6/STAT3 pathway by IL-6R antagonist, Tocilizumab or STAT3 inhibitor, S31-201 could abolish DCLK1-promoted malignant phenotypes of TNBC cells. Finally, DCLK1 was identified to be specifically and highly expressed in the mesenchymal-like subtype of TNBC and targeting DCLK1 could improve chemotherapy efficacy and activate antitumor immunity. Overall, our study revealed the potential clinical benefits of targeting DCLK1 in TNBC treatment.
A cluster randomised trial to evaluate the effectiveness of household alcohol-based hand rub for the prevention of sepsis, diarrhoea, and pneumonia in Ugandan infants (the BabyGel trial): a study protocol
Authors: Chebet Martin , Mukunya David , Burgoine Kathy , Kühl Melf-Jakob , Wang Duolao , Medina-Lara Antonieta , Faragher Eric Brian , Odiit Amos , Olupot-Olupot Peter , Stadskleiv Engebretsen Ingunn Marie , Waniaye John Baptist , Wandabwa Julius , Tylleskär Thorkild , Weeks Andrew
Published: April 2023

Background

Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months.

Methods

Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants’ homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat.

Discussion

This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits.

Trial registration

Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/.
No evidence for schistosome parasite fitness trade-offs in the intermediate and definitive host
Authors: Le Clec’h Winka , Chevalier Frédéric D. , Jutzeler Kathrin , Anderson Timothy J. C.
Published: April 2023

Background

The trematode parasite Schistosoma mansoni uses an aquatic snail intermediate and a vertebrate definitive host to complete its life cycle. We previously showed that a key transmission trait—the number of cercariae larvae shed from infected Biomphalaria spp. snails—varies significantly within and between different parasite populations and is genetically controlled by five loci. We investigated the hypothesis that the success of parasite genotypes showing high propagative fitness in the intermediate snail host may be offset by lower reproductive fitness in the definitive vertebrate host.

Methods

We investigated this trade-off hypothesis by selecting parasite progeny producing high or low number of larvae in the snail and then comparing fitness parameters and virulence in the rodent host. We infected inbred BALB/c mice using two Schistosoma mansoni parasite lines [high shedder (HS) and low shedder (LS) lines] isolated from F2 progeny generated by genetic crosses between SmLE (HS parent) and SmBRE (LS parent) parasites. We used the F3 progeny to infect two populations of inbred Biomphalaria glabrata snails. We then compared life history traits and virulence of these two selected parasite lines in the rodent host to understand pleiotropic effects of genes determining cercarial shedding in parasites infecting the definitive host.

Results

HS parasites shed high numbers of cercariae, which had a detrimental impact on snail physiology (measured by laccase-like activity and hemoglobin rate), regardless of the snail genetic background. In contrast, selected LS parasites shed fewer cercariae and had a lower impact on snail physiology. Similarly, HS worms have a higher reproductive fitness and produced more viable F3 miracidia larvae than LS parasites. This increase in transmission is correlated with an increase in virulence toward the rodent host, characterized by stronger hepato-splenomegaly and hepatic fibrosis.

Conclusions

These experiments revealed that schistosome parasite propagative and reproductive fitness was positively correlated in intermediate and definitive host (positive pleiotropy). Therefore, we rejected our trade-off hypothesis. We also showed that our selected schistosome lines exhibited low and high shedding phenotype regardless of the intermediate snail host genetic background. ​

Graphical Abstract
Diagnostic yield of genetic screening in a diverse, community-ascertained cohort
Authors: Rao Nandana D. , Kaganovsky Jailanie , Malouf Emily A. , Coe Sandy , Huey Jennifer , Tsinajinne Darwin , Hassan Sajida , King Kristine M. , Fullerton Stephanie M. , Chen Annie T. , Shirts Brian H.
Published: April 2023

Background

Population screening for genetic risk of adult-onset preventable conditions has been proposed as an attractive public health intervention. Screening unselected individuals can identify many individuals who will not be identified through current genetic testing guidelines.

Methods

We sought to evaluate enrollment in and diagnostic yield of population genetic screening in a resource-limited setting among a diverse population. We developed a low-cost, short-read next-generation sequencing panel of 25 genes that had 98.4% sensitivity and 99.98% specificity compared to diagnostic panels. We used email invitations to recruit a diverse cohort of patients in the University of Washington Medical Center system unselected for personal or family history of hereditary disease. Participants were sent a saliva collection kit in the mail with instructions on kit use and return. Results were returned using a secure online portal. Enrollment and diagnostic yield were assessed overall and across race and ethnicity groups.

Results

Overall, 40,857 people were invited and 2889 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%). The addition of more recently identified cancer risk genes increased the diagnostic yield of screening.

Conclusions

Population screening can identify additional individuals that could benefit from prevention, but challenges in recruitment and sample collection will reduce actual enrollment and yield. These challenges should not be overlooked in intervention planning or in cost and benefit analysis.
Successful management of poisoning with ivermectin (Mectizan) in the Obala health district (Centre Region, Cameroon): a case report
Authors: Donfo-Azafack Cyrille , Nana-Djeunga Hugues C. , Wafeu-Sadeu Guy , Dongmo-Yemele Raïssa , Kamgno Joseph
Published: April 2023

Background

Ivermectin (Mectizan) is an anthelmintic drug that plays a major role in the fight against two major filarial diseases, onchocerciasis and lymphatic filariasis. Unlike previous drugs that had serious and sometimes fatal side effects, ivermectin has been considered to be safe and, therefore, is widely used. Data reporting the clinical presentation of poisoning with ivermectin are very scanty, even in experimental studies.

Case presentation

In this paper, we report the case of a 19-year-old Black African female student residing in Obala (Centre Region, Cameroon) who was admitted to a health facility in Central Cameroon for a neurological disorder after intoxication with about 400 tablets of ivermectin 3 mg (~100 times the standard doses). This neurological disorder was characterized by somnolence, kinetic ataxia, increase of tendon reflex, and central visual disturbance. Management of this intoxication consisted of symptomatic treatment and monitoring of hemodynamic parameters for 5 days, with a favorable course.

Conclusions

This is the first report of a poisoning with ivermectin at ~100 times the recommended dose. This case report confirms the safety and tolerability of ivermectin, even at exceptionally high dose.