bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival benefit of surgery with postoperative radiotherapy in locally advanced cervical adenocarcinoma: a population-based analysis
Authors: Wang Xia , Lu Xiaojuan , Chen Junxing , Yi Hanjie , Lan Qiongyu
Published: October 2023

Background

The incidence of cervical adenocarcinoma (AC) has experienced a considerable increase in recent decades. Despite this, our understanding of the optimal management of locally advanced cervical AC remains limited. The present study sought to compare the clinical outcomes of radical hysterectomy with postoperative radiotherapy (PORT) and primary radiotherapy (RT) in patients with locally advanced cervical AC using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

The data were extracted from the SEER database utilizing the SEER ∗ STAT software (version 8.4.0.1). The study included patients diagnosed with locally advanced cervical AC between 2004 and 2017 with adequate information available for analysis. Patients were assigned to either the Surgery + PORT or Primary RT group based on treatment modality, and their clinical characteristics were compared. Propensity score matching (PSM) was utilized to adjust for differences in baseline characteristics between groups. The primary endpoints of the study were overall survival (OS) and cancer-specific survival (CSS).

Results

Of the 1363 patients who met the inclusion criteria, 302 (22.16%) underwent Surgery + PORT, while 1061 patients received Primary RT. The two groups differed significantly in terms of age, year of diagnosis, tumor size, grade, stage, T/N stage, and chemotherapy. PSM was performed to balance the baseline characteristics between the two groups, resulting in 594 patients being analyzed. After PSM, the Surgery + PORT group exhibited significantly improved survival rates. The 5-year OS rates were 69.7% (95% CI: 63.3%-76.9%) for the Surgery + PORT group and 60.9% (95% CI: 56.0%-66.3%) for the group receiving Primary RT (p = 0.002). The 5-year CSS rates for the two groups were 70.7% (95% CI: 64.3%-77.8%) and 66.2% (95% CI: 61.3%-71.5%), respectively (p = 0.049). Multivariate analysis revealed that Surgery + PORT was an independent favorable prognostic factor for OS (HR = 0.60, p = 0.001) and CSS (HR = 0.69, p = 0.022). Although the combined approach of surgery and PORT resulted in a favorable impact on OS in patients aged 65 years or older (HR = 0.57, p = 0.048), it did not result in a statistically significant improvement in CSS in the same age group (HR = 0.56, p = 0.087). Similarly, the combined treatment did not yield a statistically significant increase in either OS (HR = 0.78, p = 0.344) or CSS (HR = 0.89, p = 0.668) in patients with tumors larger than 60 mm.

Conclusion

The present study demonstrated that Surgery + PORT was associated with improved OS and CSS in patients with locally advanced cervical AC when compared to Primary RT. As such, Surgery + PORT may be a preferable therapeutic option for carefully selected patients with cervical AC. These findings offer valuable insight into the management of locally advanced cervical AC and may assist in personalized treatment decisions.
Exosomal miR-105-5p derived from bladder cancer stem cells targets for GPR12 to promote the malignancy of bladder cancer
Authors: Pan Gaojian , Jiang Bo , Yi Zhongquan , Yin Jiuhu , Liu Yadong
Published: October 2023

Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.
Association of SGLT-2 inhibitors with bacterial urinary tract infection in type 2 diabetes
Authors: Tanrıverdi Mustafa , Baştemir Mehmet , Demirbakan Hadiye , Ünalan Alperen , Türkmen Merve , Tanrıverdi Gülşen Özkan
Published: October 2023

Objective

We aimed to investigate the factors associated with UTI in patients with T2D whether being treated with SGLT-2i or not.

Methods

Adult patients with T2D, whose urine culture results were available, were analyzed retrospectively. Urine culture was obtained from mid-flow urine. Antibacterial treatment was given to the patients with UTI, which was defined by positive urine cultures and/or clinical findings. We grouped the patients as follows: Group A, those treated with SGLT-2i; and Group B, those not treated with SGLT-2i.

Results

A total of 101 patients were included. Median age was 56 (45–67), 56.4% (n = 57) of the patients were female. Urine culture was positive in 54.9% (n = 28) and 16% (n = 8) of Group A (n = 51) and Group B (n = 50), respectively. Of those for whom urine culture was positive, Escherichia coli was isolated in 83.3% (n = 30), and both Escherichia coli and Klebsiella pneumoniae (K.pneumoniae) were isolated in 16.7% (n = 6). Klebsiella pneumoniae was isolated only from Group A. The need for and duration of hospitalization were higher in Group A (p < 0.001). UTI was detected in 60 patients. ROC analysis showed that a HbA1c of > 5.8% was associated with UTI with good accuracy (AUC: 0.835, p < 0.001). In multiple logistic regression analysis, SGLT-2i use and glucosuria were positive predictors for UTI (p = 0.004, Odds Ratio: 1984.013; and p = 0.028, and Odds Ratio: 12.480, respectively).

Conclusion

Besides the association of HbA1c and BMI with UTI, SGLT-2i use and glucosuria predicted UTI. Urine culture is important with respect to the choice of antibacterial treatment, especially in those patients under SGLT-2i treatment. The effect of SGLT-2i on the development of UTI is independent of baseline BMI score or HbA1c.
Zingiber officinale rhizome extracts mediated ni nanoparticles and its promising biomedical and environmental applications
Authors: Abdullah  , Hussain Tahir , Faisal Shah , Rizwan Muhammad , Almostafa Mervt M. , Younis Nancy S. , Yahya Galal
Published: October 2023

Background

Zingiber officinale, generally known as ginger, contains bioactive phytochemicals, including gingerols and shogaols, that may function as reducing agents and stabilizers for the formation of nickel nanoparticles (Ni-NPs). Ginger extract-mediated nickel nanoparticles were synthesized using an eco-friendly method, and their antibacterial, antioxidant, antiparasitic, antidiabetic, anticancer, dye degrading, and biocompatibility properties were investigated.

Methods

UV–visible spectroscopy, fourier transform infrared spectroscopy, X-ray powder diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy were used to validate and characterize the synthesis of Ni-NPs. Agar well diffusion assay, alpha-amylase and glucosidase inhibitory assay, free radical scavenging assay, biocompatibility assay, and MTT assay were used to analyse the biomedical importance of Ni-NPs.

Results

SEM micrograph examinations revealed almost aggregates of Ni-NPs; certain particles were monodispersed and spherical, with an average grain size of 74.85 ± 2.5 nm. Ni-NPs have successfully inhibited the growth of Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris by inducing membrane damage, as shown by the absorbance at 260 nm (A260). DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals were successfully scavenged by Ni-NPs at an inhibition rate of 69.35 ± 0.81% at 800 µg/mL. A dose-dependent cytotoxicity of Ni-NPs was observed against amastigote and promastigote forms of Leishmania tropica, with significant mortality rates of 94.23 ± 1.10 and 92.27 ± 1.20% at 1.0 mg/mL, respectively. Biocompatibility studies revealed the biosafe nature of Ni-NPs by showing RBC hemolysis up to 1.53 ± 0.81% at 400 µg/mL, which is considered safe according to the American Society for Materials and Testing (ASTM). Furthermore, Ni-NPs showed antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes at an inhibition rate of 22.70 ± 0.16% and 31.23 ± 0.64% at 200 µg/mL, respectively. Ni-NPs have shown significant cytotoxic activity by inhibiting MCF-7 cancerous cells up to 68.82 ± 1.82% at a concentration of 400 µg/mL. The IC50 for Ni-NPs was almost 190 µg/mL. Ni-NPs also degraded crystal violet dye up to 86.1% at 2 h of exposure.

Conclusions

In conclusion, Zingiber officinale extract was found successful in producing stable nanoparticles. Ni-NPs have shown substantial biomedical activities, and as a result, we believe these nanoparticles have potential as a powerful therapeutic agent for use in nanomedicine.
Knowledge of common cancers among new-entry health science students in Japan and Vietnam
Authors: Vu Nhu Thi Hanh , Tran Tam Thao Tuyet , Quach Duc Trong , Miyauchi Shunsuke , Yoshida Mahoko , Okamoto Yuri , Lu Dat Minh , Tran Linh Le , Luu Mai Ngoc , Hiyama Toru
Published: October 2023

Background

The incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions.

Methods

This cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer.

Results

A total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p < 0.001), except for human papillomavirus (HPV) infection awareness. For this understanding, only 14.8% of Japanese students selected the correct answer, which was significantly lower than the 22.4% of Vietnamese students (p = 0.001). Both the Japanese and Vietnamese students had limited knowledge regarding the connection between HPV infection and cancer and the link between estrogen–progestogen menopausal therapy and breast cancer. Additionally, female students had better knowledge about breast, skin, and endometrial cancers than male students.

Conclusions

Japanese students generally exhibited higher levels of cancer knowledge than Vietnamese students, except for HPV infection recognition. Both groups had limited knowledge regarding the connection between HPV infection and cancer and the relationship between estrogen–progestogen menopausal therapy and breast cancer.
Which virtual education methods do e‑students prefer? Design and validation of Virtual Education Preferences Questionnaire (VEPQ)
Authors: Karimian Zahra , Barkhor Asieh , Mehrabi Manoosh , Khojasteh Laleh
Published: October 2023

Background

With the prevalence of new technologies and evolving student learning styles, virtual teaching methods have become increasingly popular. As a result, more and more students are opting to learn online. However, one common concern is that they may feel disconnected from their teachers, leading to feelings of loneliness and doubts about the quality of education they are receiving. To address this issue, a study was conducted to gather data on students' preferences for virtual education and to validate a tool for measuring students' preferences for virtual education.

Methods

The research was conducted in a mixed method with a quantitative–qualitative sequence. A virtual education preferences questionnaire (VEPQ) for students with a total of 17 items was created and validated as part of the qualitative component by looking at the theoretical underpinnings and experts' opinions in the focus group. The scale of the six-point Likert questionnaire was from very high to very low. To validate the tool and determine preferences, exploratory factor analysis was used. A total of 155 samples answered the questions and the data were analyzed using SPSS-24 software.

Results

A total of 155 complete questionnaires were returned; among them, 110 (71%) were filled out by women, 73 (47.1%) by respondents between the ages of 36 and 45, 107 (69%) were already employed in paramedical fields, and 48 (31%) were enrolled in a medical school. The opinions of ten experts were used to confirm the face validity of the questionnaire. With CVI = 0.924 and CVR = 0.805, content validity was verified. Using the internal consistency method of the questions with a Cronbach's alpha coefficient of R = 0.824, the validity of the entire questionnaire was confirmed. Exploratory factor analysis revealed that a total of five components—self-directed projects (29.58%), e-content (13.00%), online presentation (10.97%), face-to-face interactions (9.12%), and text interactions (7.11%) had the highest load, with a total of 69.77% of the structure explaining virtual education preferences. The factor analysis test and the suitability of the sample are both confirmed by the value of KMO = 0.721 and the significance of Pvalue < 0.001.

Conclusion

It appears that the highly valid tool developed can be used to ascertain the educational preferences of students. Also, the high factor load of self-directed educational methods and e-content shows that independence and flexibility in time and place are more important for students.
Exploring the viewpoint of faculty members of medical sciences universities about effective factors on their organizational retention: a qualitative study
Authors: Mohammadi Elaheh , Salajegheh Mahla
Published: October 2023

Background and aim

Faculty retention in medical sciences universities is one of the most important values for the survival of the educational system. This study aimed to explore the viewpoint of faculty members of medical sciences universities in Iran about effective factors affecting their organizational retention.

Methods

Qualitative study using deep interviews collected by maximum variation sampling. A purposively selected sample of 15 faculty members was recruited throughout two Iranian medical sciences universities (Tehran University of Medical Sciences and Kerman University of Medical Sciences) during 2021-22.

Results

Qualitative data analysis provided 3 main categories and 10 sub-categories. Three main categories were identified that affected the faculty’s organizational retention included individual factors, institutional factors, and socio-political factors.

Conclusion

Factors that contribute to the improvement of faculty retention encompass various aspects. These include consideration given to the personal and social requirements of faculty members, support provided by the organization along with effective resource management, a fair and transparent organizational structure, and the maintenance of political stability both within the university and the nation.
Development and evaluation of a point-of-care ocular ultrasound curriculum for medical students - a proof-of-concept study
Authors: Weimer Johannes Matthias , Rink Maximilian , Vieth Thomas , Lauff Jonas , Weimer Andreas , Müller Lukas , Stäuber Marie , Reder Sebastian R. , Buggenhagen Holger , Bellhäuser Henrik , Kloeckner Roman , Künzel Julian , Hoffmann Esther M. , Würde Anna
Published: October 2023

Background

Point-of-care Ocular Ultrasound (POCOUS) has gained importance in emergency medicine and intensive care in recent years. This work aimed to establish and evaluate a dedicated ultrasound education program for learning POCOUS-specific skills during medical studies at a university hospital.

Methods

The blended learning-based program (6 teaching units) based on recent scientific publications and recommendations was developed for students in the clinical part of their medical studies. Experts and trainers consisted of physicians from the Ear-Nose-Throat, radiology, ophthalmology and neurology specialties as well as university educational specialists. Lecture notes containing digital video links for preparation was produced as teaching material. In total, 33 students participated in the study. The education program, including the teaching materials, motivation and subjective gain in competency, was evaluated with the aid of a questionnaire (7-point Likert response format). Objective learning success was assessed on the basis of pre- and post-tests. These covered the skill areas: “anatomical basics”, “ultrasound basics”, “understanding of cross-sectional images”, “normal findings” and “pathology recognition”.

Results

In the objective assessment of image interpretation, the participants improved significantly (p < 0.001) from pre- to post-test with a large effect size (Cohen’s d = 1.78, effect size r = 0.66). The evaluations revealed a high level of satisfaction with the course concept, teaching materials and the tutors. In addition, a high level of motivation was recorded in relation to continuing to study “ultrasound diagnostics” and “ophthalmologic diseases”. A significant (p < 0.01) positive gain was also achieved in terms of the subjective assessment of competency. This covers areas such as expertise, sonographic anatomy and performing a POCOUS examination as well as recognizing retinal detachment, globe perforation and increased optic nerve sheath diameter.

Conclusion

The results of this feasibility study show that medical students accept and support a POCOUS-specific education program and are able to develop a higher objective and subjective level of competency. Future transfer to other sites and larger groups of participants seems feasible.
Screening of antigenic epitopes related to the adhesion of the avian Escherichia coli Type 1 Fimbrial Agglutinin Domain
Authors: Chen Junhong , Dai Wei , Cui Shengling , Lei Weiqiang , Dai Dingzhen
Published: October 2023

Background

Avian Escherichia coli (E.coli) type 1 fimbriae adhere to avian tracheal epithelial cells through the FimH protein. However, the adhesion-related antigen is still unknown. The purpose of this study was to analyze the antigenicity of the type 1 fimbrial FimH protein of wild-type avian E. coli, screen antigen epitopes, and prepare monoclonal antibodies (mAbs) that can block the adhesion of avian E. coli.

Results

In this study, the nucleic acid homologies of MG2 (O11), TS12 (O18), and YR5 (O78) with K12 were 97.7%, 99.6%, and 97.7%, respectively, and the amino acid sequence similarity reached 98.7%, 99.3%, and 98.0%, respectively. The epitopes and hydrophilicities of the FimH proteins of these three strains were similar. The more obvious lectin domain epitopes were located at FimH protein positions 111–124 and 154–162. The mAbs 7C2 and 7D8 against these two epitopes were prepared. An adhesion inhibition test showed that 7C2 and 7D8 blocked bacterial adhesion to avian tracheal epithelial cells. The mAb 7C2 against the 111–124 epitope inhibited O78 strain adhesion by 93%, and the mAb 7D8 against the 154–162 epitope inhibited O78 strain adhesion by 49%, indicating that these two epitopes are closely related to the adhesion of type 1 fimbriae. However, only the 111–124 epitope-recognizing mAb 7C2 inhibited bacterial agglutination of erythrocytes, indicating that host cell receptor binding and erythrocyte agglutination are not mediated by the same spatial locations within the FimH protein.

Conclusions

The results demonstrate that the mAbs 7C2 and 7D8 against FimH protein positions 111–124 and 154–162 could inhibit the adhesion of E.coli to the chicken trachea.
Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures
Authors: Figiel Sandy , Yin Wencheng , Doultsinos Dimitrios , Erickson Andrew , Poulose Ninu , Singh Reema , Magnussen Anette , Anbarasan Thineskrishna , Teague Renuka , He Mengxiao , Lundeberg Joakim , Loda Massimo , Verrill Clare , Colling Richard , Gill Pelvender S. , Bryant Richard J. , Hamdy Freddie C. , Woodcock Dan J. , Mills Ian G. , Cussenot Olivier , Lamb Alastair D.
Published: October 2023

Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.
Fecal short chain fatty acids and urinary 3-indoxyl sulfate do not discriminate between patients with Crohn´s disease and ulcerative colitis and are not of diagnostic utility for predicting disease severity
Authors: Tews Hauke Christian , Elger Tanja , Gunawan Stefan , Fererberger Tanja , Sommersberger Stefanie , Loibl Johanna , Huss Muriel , Liebisch Gerhard , Müller Martina , Kandulski Arne , Buechler Christa
Published: October 2023

Background

Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity.

Methods

SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC–MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age.

Results

Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable.

Conclusions

Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.
Bioinspired nanovesicles released from injectable hydrogels facilitate diabetic wound healing by regulating macrophage polarization and endothelial cell dysfunction
Authors: Zhang Weiyue , Yang Xueyang , Huang Xin , Chen Lulu
Published: October 2023

Wound healing is one of the major global health concerns in diabetic patients. Overactivation of proinflammatory M1 macrophages could lead to delayed wound healing in diabetes. 4-octyl itaconate (4OI), a derivative of the metabolite itaconate, has aroused growing interest recently on account of its excellent anti-inflammatory properties. Cell membrane coating is widely regarded as a novel biomimetic strategy to deliver drugs and inherit properties derived from source cells for biomedical applications. Herein, we fused induced pluripotent stem cell-derived endothelial cell (iEC) membrane together with M1 type macrophage membrane to construct a hybrid membrane (iEC-M) camouflaged 4OI nanovesicles (4OI@iEC-M). Furthermore, bioinspired nanovesicles 4OI@iEC-M are incorporated into the injectable, multifunctional gelatin methacryloyl hydrogels for diabetic wound repair and regeneration. In our study, bioinspired nanovesicles could achieve dual-targeted deliver of 4OI into both M1 macrophages and endothelial cells, thereby promoting macrophage polarization and protecting endothelial cells. With the synergistically anti-inflammatory and immunoregulative effects, the bioinspired nanovesicles-loaded hydrogels could facilitate neovascularization and exhibit superior diabetic wound repair and regeneration. Taken together, this study might provide a novel strategy to facilitate diabetic wound healing, thereby reducing limb amputation and mortality of diabetes.
A longitudinal multi-site evaluation of community-based partnerships: implications for researchers, funders, and communities
Authors: Lewis Virginia J. , Scott Catherine M. , Silburn Kate , Miller William L.
Published: October 2023

Background

Innovative Models Promoting Access to Care Transformation (IMPACT) was a five-year (2013–2018), Canadian-Australian research program that aimed to use a community-based partnership approach to transform primary health care (PHC) organizational structures to improve access to appropriate care for vulnerable populations. Local Innovation Partnerships (LIPs) were developed to support the IMPACT research program, and to be ongoing structures that would continue to drive local improvements to PHC.

Methods

A longitudinal development-focused evaluation explored the overall approach to governance, relationships and processes of the LIPs in the IMPACT program. Semi-structured interviews were conducted with purposively selected participants including researchers with implementation roles and non-researchers who were members of LIPs at four time points: early in the development of the LIPs in 2014; during intervention development in 2015/2016; at the intervention implementation phase in 2017; and nearing completion of the research program in 2018.  A hybrid deductive-inductive thematic analysis approach was used. A Guide developed to support the program was used as the framework for designing questions and analysing data using a qualitative descriptive method initially. A visual representation was developed and refined after each round of data collection to illustrate emerging themes around governance, processes and relationship building that were demonstrated by IMPACT LIPs. After all rounds of data collection, an overarching cross-case analysis of narrative summaries of each site was conducted.

Results

Common components of the LIPs identified across all rounds of data collection related to governance structures, stakeholder relationships, collaborative processes, and contextual barriers.  LIPs were seen primarily as a structure to support implementation of a research project rather than an ongoing multisectoral community-based partnership.  LIPs had relationships with many and varied stakeholders although not necessarily in ways that reflected the intended purpose. Collaboration was valued, but multiple barriers impeded the ability of LIPs to enact real collaboration in daily operations over time. We learned that experience, history, and time matter, especially with respect to community-oriented collaborative skills, structures, and relationships.

Conclusions

This longitudinal multiple case study offers lessons and implications for researchers, funders, and potential stakeholders in community-based participatory research.
Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus
Authors: He Xu , Yao Wei , Zhu Ji-Ding , Jin Xin , Liu Xin-Yuan , Zhang Kang-Jian , Zhao Shou-Liang
Published: October 2023

Background

Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet.

Methods

The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays.

Results

hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods.

Conclusions

These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.
Development of a foot and ankle strengthening program for the treatment of plantar heel pain: a Delphi consensus study
Authors: Osborne John W. A. , Menz Hylton B. , Whittaker Glen A. , Landorf Karl B.
Published: October 2023

Background

People with plantar heel pain (PHP) have reduced foot and ankle muscle function, strength and size, which is frequently treated by muscle strengthening exercises. However, there has been little investigation of what exercises are used and there is no sound evidence base to guide practice. This study aimed to develop a consensus‐driven progressive muscle strengthening program for PHP.

Methods

Thirty‐eight experts were invited to participate in the study over three rounds. Round 1 was an open‐ended questionnaire that provided the core characteristics of progressive strengthening programs designed for three different adult patient types with PHP (younger athletic, overweight middle‐aged, older), which were presented as vignettes. In Round 2, experts indicated their agreement to the proposed exercises and training variables. In Round 3, experts were presented with amendments to the exercises based on responses from Round 2 and indicated their agreement to those changes. Consensus was achieved when > 70% of experts agreed.

Results

Two experts were ineligible and 12 declined, leaving 24 (67%) who participated in Round 1. Eighteen (75%) completed all three rounds. From Round 1, progressive strengthening programs were developed for the three vignettes, which included 10 different exercises and three training variables (sets / repetitions, weight, and frequency). In Round 2, 68% (n = 17) of exercises and 96% (n = 72) of training variables reached consensus. In Round 3, only exercise changes were presented and 100% of exercises reached consensus.

Conclusions

This study provides three progressive strengthening programs agreed to by experts that can be used in future clinical trials to determine the effectiveness of muscle strengthening for PHP. In addition, clinicians could use the programs as part of a rehabilitation strategy with the caveat that they may change as more research is conducted.
Critical appraisal beyond clinical guidelines for intraabdominal candidiasis
Authors: Maseda Emilio , Martín-Loeches Ignacio , Zaragoza Rafael , Pemán Javier , Fortún Jesús , Grau Santiago , Aguilar Gerardo , Varela Marina , Borges Marcio , Giménez María-José , Rodríguez Alejandro
Published: October 2023

Background

Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.

Main body

This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.

Conclusion

There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.
Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs
Authors: Watson Joshua , Wang Tianfang , Ho Kun-Lin , Feng Yuan , Mahawan Tanakamol , Dobbin Kevin K. , Zhao Shaying
Published: October 2023

Background

About 20% of breast cancers in humans are basal-like, a subtype that is often triple-negative and difficult to treat. An effective translational model for basal-like breast cancer is currently lacking and urgently needed. To determine whether spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog–human molecular homology at the subtype level.

Methods

We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We identified feature genes for human BLBC and luminal A subtypes via machine learning and used these genes to repeat canine-alone and cross-species tumor classifications. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog–human subtype comparison.

Results

Our independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 and feature gene classifications, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched in histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER−) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER−PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors and with the expression of T cell exhaustion markers (e.g., PDCD1) in ER−PR+ canine tumors.

Conclusions

We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall and thus could serve as a vital translational model of this devastating breast cancer subtype. Our study also sheds light on the dog–human difference in the mammary tumor histology and the hormonal cycle.
Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome
Authors: Gatto Antonio , Capossela Lavinia , Conti Giorgio , Eftimiadi Gemma , Ferretti Serena , Manni Luigi , Curatola Antonietta , Graglia Benedetta , Di Sarno Lorenzo , Calcagni Maria Lucia , Di Giuda Daniela , Cecere Stefano , Romeo Domenico Marco , Soligo Marzia , Picconi Enzo , Piastra Marco , Della Marca Giacomo , Staccioli Susanna , Ruggiero Antonio , Cocciolillo Fabrizio , Pulitanò Silvia , Chiaretti Antonio
Published: October 2023

Background

Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS.

Methods

Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.

Results

Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported.

Conclusion

These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.
Direct interspecies electron transfer mechanisms of a biochar-amended anaerobic digestion: a review
Authors: Valentin Marvin T. , Luo Gang , Zhang Shicheng , Białowiec Andrzej
Published: October 2023

This paper explores the mechanisms of biochar that facilitate direct interspecies electron transfer (DIET) among syntrophic microorganisms leading to improved anaerobic digestion. Properties such as specific surface area (SSA), cation exchange capacity (CEC), presence of functional groups (FG), and electrical conductivity (EC) were found favorable for increased methane production, reduction of lag phase, and adsorption of inhibitors. It is revealed that these properties can be modified and are greatly affected by the synthesizing temperature, biomass types, and residence time. Additionally, suitable biochar concentration has to be observed since dosage beyond the optimal range can create inhibitions. High organic loading rate (OLR), pH shocks, quick accumulation and relatively low degradation of VFAs, and the presence of heavy metals and toxins are the major inhibitors identified. Summaries of microbial community analysis show fermentative bacteria and methanogens that are known to participate in DIET. These are Methanosaeta, Methanobacterium, Methanospirillum, and Methanosarcina for the archaeal community; whereas, Firmicutes, Proteobacteria, Synergistetes, Spirochetes, and Bacteroidetes are relatively for bacterial analyses. However, the number of defined cocultures promoting DIET is very limited, and there is still a large percentage of unknown bacteria that are believed to support DIET. Moreover, the instantaneous growth of participating microorganisms has to be validated throughout the process.

Graphical abstract
Teleost genomic repeat landscapes in light of diversification rates and ecology
Authors: Reinar William B. , Tørresen Ole K. , Nederbragt Alexander J. , Matschiner Michael , Jentoft Sissel , Jakobsen Kjetill S.
Published: October 2023

Repetitive DNA make up a considerable fraction of most eukaryotic genomes. In fish, transposable element (TE) activity has coincided with rapid species diversification. Here, we annotated the repetitive content in 100 genome assemblies, covering the major branches of the diverse lineage of teleost fish. We investigated if TE content correlates with family level net diversification rates and found support for a weak negative correlation. Further, we demonstrated that TE proportion correlates with genome size, but not to the proportion of short tandem repeats (STRs), which implies independent evolutionary paths. Marine and freshwater fish had large differences in STR content, with the most extreme propagation detected in the genomes of codfish species and Atlantic herring. Such a high density of STRs is likely to increase the mutational load, which we propose could be counterbalanced by high fecundity as seen in codfishes and herring.
Medicaid policy data for evaluating eligibility and programmatic changes
Authors: Shafer Paul R. , Katchmar Amanda , Callori Steven , Alam Raisa , Patel Roshni , Choi Sugy , Auty Samantha
Published: October 2023

Objectives

Medicaid and the Children’s Health Insurance Program (CHIP) provide health insurance coverage to more than 90 million Americans as of early 2023. There is substantial variation in eligibility criteria, application procedures, premiums, and other programmatic characteristics across states and over time. Analyzing changes in Medicaid policies is important for state and federal agencies and other stakeholders, but such analysis requires data on historical programmatic characteristics that are often not available in a form ready for quantitative analysis. Our objective is to fill this gap by synthesizing existing qualitative policy data to create a new data resource that facilitates Medicaid policy research.

Data description

Our source data were the 50-state surveys of Medicaid and CHIP eligibility, enrollment, and cost-sharing policies, and budgets conducted near annually by KFF since 2000, which we coded through 2020. These reports are a rich source of point-in-time information but not operationalized for quantitative analysis. Through a review of the measures captured in the KFF surveys, we developed five Medicaid policy domains with 122 measures in total, each coded by state-quarter—1) eligibility (28 measures), 2) enrollment and renewal processes (39 measures), 3) premiums (16 measures), 4) cost-sharing (26 measures), and 5) managed care (13 measures).
The impact of helminth-induced immunity on infection with bacteria or viruses
Authors: Chen Hong , Cao Zengguo , Liu Mingyuan , Diamond Michael S. , Jin Xuemin
Published: October 2023

Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, TH1 cells), whereas infection by helminths typically elicits a type II host resistance and tolerizing immune response (e.g., IL-4, IL-5, IL-13, TH2 cells). In some respects, the type I and II immune responses induced by these different classes of pathogens are antagonistic. Indeed, recent studies indicate that infection by helminths differentially shapes the response and outcome of subsequent infection by viruses and bacteria. In this review, we summarize the current knowledge on how helminth infections influence concurrent or subsequent microbial infections and also discuss the implications for helminth-mediated immunity on the outcome of SARS-CoV-2 disease.