bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of subsolid pulmonary nodule growth rate using radiomics
Authors: Ma Zong Jing , Ma Zhuang Xuan , Sun Ying Li , Li De Chun , Jin Liang , Gao Pan , Li Cheng , Li Ming
Published: November 2023

Background

Pulmonary nodule growth rate assessment is critical in the management of subsolid pulmonary nodules (SSNs) during clinical follow-up. The present study aimed to develop a model to predict the growth rate of SSNs.

Methods

A total of 273 growing SSNs with clinical information and 857 computed tomography (CT) scans were retrospectively analyzed. The images were randomly divided into training and validation sets. All images were categorized into fast-growth (volume doubling time (VDT) ≤ 400 days) and slow-growth (VDT > 400 days) groups. Models for predicting the growth rate of SSNs were developed using radiomics and clinical features. The models’ performance was evaluated using the area under the curve (AUC) values for the receiver operating characteristic curve.

Results

The fast- and slow-growth groups included 108 and 749 scans, respectively, and 10 radiomics features and three radiographic features (nodule density, presence of spiculation, and presence of vascular changes) were selected to predict the growth rate of SSNs. The nomogram integrating radiomics and radiographic features (AUC = 0.928 and AUC = 0.905, respectively) performed better than the radiographic (AUC = 0.668 and AUC = 0.689, respectively) and radiomics (AUC = 0.888 and AUC = 0.816, respectively) models alone in both the training and validation sets.

Conclusion

The nomogram model developed by combining radiomics with radiographic features can predict the growth rate of SSNs more accurately than traditional radiographic models. It can also optimize clinical treatment decisions for patients with SSNs and improve their long-term management.
Glomerular lipidosis as a feature of renal-limited macrophage activation syndrome in a transplanted kidney: a case report
Authors: Sugisaki Kentaro , Uchida Takahiro , Iwama Sachiko , Okihara Masaaki , Akashi Isao , Kihara Yu , Konno Osamu , Kuroda Masayuki , Koike Junki , Iwamoto Hitoshi , Oda Takashi
Published: November 2023

Background

Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.

Case presentation

A 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient’s extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.

Conclusion

To our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.
Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study
Authors: Hau Sofie Olsson , Svensson Maja , Petersson Alexandra , Eberhard Jakob , Jirström Karin
Published: November 2023

Background

There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).

Methods

Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.

Results

In total nine proteins; chemokine (C–C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman’s Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19–9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.

Conclusions

This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as “chemo brain”. It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.

Trial registration

Clinical Trial Registration: NCT03724994.
Measurement of the apical anatomy of immature maxillary central incisors using cone-beam computed tomography
Authors: Wang Linlin , Qin Xiurong , Pang Yongzhi , Ma Yuxin , Fan Mingru , Tian Hongsheng
Published: November 2023

Objective

To investigate the CBCT findings of the apical anatomy of immature maxillary central incisors.

Methods

CBCT images of 100 immature maxillary central incisors in Nolla 8 and 100 immature maxillary central incisors in Nolla 9 were collected. The mesiodistal and carniocaudal diameters of the apical foramen of immature maxillary central incisors were measured by software included with CBCT, as well as the mesiodistal, carniocaudal and facioligual diameters of the apical shadow. The apical shadow and apical foramen diameters were compared between Nolla 8 and Nolla 9. Data were analyzed using the MedCalc software package.

Results

For immature maxillary central incisors, the mesiodistal and facioligual diameters of the apical foramen were 2.75±0.68 mm and 3.28±0.74 mm in Nolla 8 and 1.50±0.51 mm and 1.92±0.79 mm in Nolla 9. The mesiodistal, facioligual and carniocaudal diameters of the apical shadow were 3.84±0.73 mm, 4.49±0.68 mm and 3.41±1.27 mm in Nolla 8 and 2.76±0.60 mm, 3.41±0.80 mm and 2.06±0.65 mm in Nolla 9, respectively.

Conclusions

The immature maxillary central incisors in Nolla 8 have a larger apical shadow and apical foramen than those in Nolla 9. The apical region of the maxillary central incisors in Nolla 8 was more likely to have a broad, blurred lamina dura. With the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp.

Clinical significance

To our knowledge, this is the first study to radiologically analyse the in vivo anatomy of the apical foramen and apical shadow of immature maxillary central incisors. The results of this study provide a more detailed understanding of the apical anatomy of the immature maxillary central incisor for the diagnosis and treatment of apical lesions.
Implementation strategies, facilitators, and barriers to scaling up and sustaining demand generation in family planning, a mixed-methods systematic review
Authors: Nabhan Ashraf , Kabra Rita , Ashraf Alyaa , Elghamry Fatma , Kiarie James ,   Family Planning Research Collaborators, Atwa Emry , Bahnasy Samhaa , Elgendi Marwa , Elshabrawy Amal , Eltayeb Salma , Galal Sara , Kodsy Mariam , Makram Nada , Mostafa Nourhan , Sakna Noha , Salama Mohamed , Snosi Marwa , Wagih Nouran , Zenhom Ahmed
Published: November 2023

Background

Demand generation aims to increase clients’ desire to use family planning. The aim of this work was to systematically summarize strategies, facilitators, and barriers to scaling up and sustaining demand generation in family planning.

Methods

We searched electronic bibliographic databases from inception to October 2022. We included quantitative, qualitative, and mixed methods reports on demand generation strategies in family planning, regardless of country, language, publication status, or methodological limitations. We assessed abstracts, titles and full-text papers according to the inclusion criteria, extracted data, and assessed methodological quality of included reports. We used the convergent integrated approach and a deductive thematic synthesis to summarize demand generation themes and subthemes. We used the health system building blocks to synthesize the factors affecting implementation (barriers and facilitators). We used GRADE-CERQual to assess our confidence in the findings.

Results

Forty-six studies (published 1990–2022) were included: forty-one quantitative, one qualitative, and four mixed methods). Three were from one high-income country, and forty three from LMIC settings. Half of reports were judged to be of unclear risk of bias. There were unique yet interrelated strategies of scaling-up demand generation for family planning. Interpersonal communication strategies increase adoption and coverage of modern contraceptive methods, but the effect on sustainability is uncertain. Mass media exposure increases knowledge and positive attitudes and may increase the intention to use modern contraceptive methods. Demand-side financing approaches probably increase awareness of contraceptives and the use of modern contraceptive methods among poor clients. Multifaceted Demand generation approaches probably improve adoption, coverage and sustainability of modern methods use. Factors that influence the success of implementing these strategies include users knowledge about family planning methods, the availability of modern methods, and the accessibility to services.

Conclusions

Demand generation strategies may function independently or supplement each other. The myriad of techniques of the different demand generation strategies, the complexities of family planning services, and human interactions defy simplistic conclusions on how a specific strategy or a bundle of strategies may succeed in increasing and sustaining family planning utilization.

Trial Registration

Systematic review registration: Center for Open Science, osf.io/286j5
Prognostic impact of PTK6 expression in triple negative breast cancer
Authors: Chen Yuexia , Qu Wei , Tu Jianhong , Yang Liu , Gui Xingxing
Published: November 2023

Background

The aim of this study was to investigate the expression of PTK6 in different groups of triple negative breast cancer and its impact on prognosis.

Methods

Retrospective study of a total of 209 surgical specimens of breast cancer were identified by IHC or FISH methods as triple negative,and divided into a lymph node metastasis positive (LNM +)group (n = 102) and a lymph node metastasis negative(LNM-) group (n = 107) according to the lymph node status of the surgical specimen. PTK6 expression was detected by IHC technique in all surgical specimens. PTK6 expression and clinicopathological features was explored by Chi-square test. The prognosis of different groups of patients was analyzed by Kaplan–Meier survival analysis and COX analysis.

Results

The incidence of PTK6 expression in the LNM + group (78.4%) was significantly higher than in the LNM- group (28%). Clinicopathological analysis showed that PTK6 expression in the LNM + group was negatively correlated with the 5-year survival of patients. Kaplan–Meier analysis showed that only PTK6 expression in the LNM + group was negatively correlated with OS and DFS. COX analysis also showed that PTK6 expression and N stage were independent prognostic factors for DFS in the LNM + group. No correlation was observed between HER2 and PTK6 expression in any of the groups.

Conclusions

This study suggests that PTK6 promotes tumor development and was associated with poor prognosis in the LNM + group of triple negative breast cancer. Inhibition of PTK6 may be a new approach for the treatment of triple negative breast cancer patients, especially those with metastasis.
RETRACTED ARTICLE: Effect of Oroxylum indicum on hepatocellular carcinoma via the P53 and VEGF pathways based on microfluidic chips
Authors: Luo Xi , Zhao Miao , Liu Sicong , Zheng Yi , Zhang Qiang , Bao Yong-rui , Wang Shuai , Li Tian-jiao , Meng Xian-sheng
Published: November 2023

Background

Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer cell migration, invasion, and neovascularization need to be further studied. Consumption of flavonoid-rich Oroxylum indicum (OI) has been associated with multiple beneficial effects, including anti-inflammatory and anticancer properties, but the potential effects on HCC have not been thoroughly investigated.

Objective

In this study, we aimed to reveal the effect of OI on HCC and its potential mechanism through microfluidic technology.

Methods

We designed microfluidic chips for cell migration, invasion, and neovascularization to evaluate the effect of OI on HepG2 cells. To further explore the mechanism of its anti-liver cancer action, the relevant signaling pathways were studied by microfluidic chips, RT‒qPCR and immunofluorescence techniques. Compared to the control group, cell migration, invasion, and angiogenesis were significantly reduced in each administration group. According to the P53 and VEGF pathways predicted by network pharmacology, RT‒qPCR and immunofluorescence staining experiments were conducted.

Results

The results showed that OI upregulated the expression of Bax, P53 and Caspase-3 and downregulated the expression of Bcl-2 and MDM2. It has been speculated that OI may directly or indirectly induce apoptosis of HepG2 cells by regulating apoptosis-related genes. OI blocks the VEGF signaling pathway by downregulating the expression levels of VEGF, HIF-1α and EGFR and inhibits the migration and invasion of HepG2 cells and the formation of new blood vessels.

Conclusion

Our findings suggest that OI may inhibit the migration, invasion, and neovascularization of HepG2 cells, and its regulatory mechanism may be related to the regulation of the P53 and VEGF pathways.
The pattern of herbal medicines use for breastfeeding mother in Jogonalan, Klaten, Indonesia: a mini survey
Authors: Sayuti Nutrisia Aquariushinta , Atikah Nur
Published: November 2023

Background and objectives

Indonesian society extensively uses herbal medicine due to its abundant natural resources that have been utilized for generations for health purposes. Herbal medicine is also employed by specific community groups, such as breastfeeding mothers, to address issues like low milk production. However, there has yet to be much research conducted on its usage patterns in the Jogonalan District, Klaten Regency, Indonesia. It is crucial to understand this aspect to gain an overview of herbal medicine utilization in the community, thus preserving local’s healthy traditional culture and traditions and continuing their development. This study aims to describe the pattern of herbal medicine usage among breastfeeding mothers in the Jogonalan District, Klaten Regency, Central Java Province, Indonesia.

Methods

The quantitative descriptive study conducted as a mini survey to breastfeeding mothers who used herbs, visited minimal three (3) times in integrated service posts for babies/toddlers in the Jogonalan sub-district and agree to overcome the research. Calculating the frequency distribution was used to analyze the study's findings. The advantages and disadvantages of these results are evaluated in relation to the findings of earlier investigations.

Results and conclusions

The respondents were dominated housewives (84.4%), aged 20–35 years (71.1%), had secondary education (60.0%), and multiparous (66.7%). The daily use ofuyub-uyubas a breast milk enhancer dominates the pattern of herbal medicine use. Papaya leaves, turmeric, and aromatic ginger are further herbal remedies. Nursing mothers’ health and fitness and breastfed children’s health is other advantages. The only adverse effects reported by three respondents (6.7%) were nausea and dizziness. Breastfeeding mothers can safely utilize evidence-based herbal medicines by increasing their knowledge, consulting with health professionals, and using them under supervision to preserve their use.
Construct validity of a questionnaire for measuring student engagement in problem-based learning tutorials
Authors: Kassab Salah Eldin , El-Baz Amany , Hassan Nahla , Hamdy Hossam , Mamede Silvia , Schmidt Henk G.
Published: November 2023

Background

Student engagement is student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. Although previous studies provided some evidence of measuring student engagement in PBL tutorials, there are no existing quantitative studies in which cognitive, behavioral, and emotional engagement of students in PBL tutorials is measured. Therefore, this study aims to develop and examine the construct validity of a questionnaire for measuring cognitive, behavioral, and emotional engagement of students in PBL tutorials.

Methods

A 15-item questionnaire was developed guided by a previously published conceptual framework of student engagement. Focus group discussion (n = 12) with medical education experts was then conducted and the questionnaire was piloted with medical students. The questionnaire was then distributed to year 2 and 3 medical students (n = 176) in problem-based tutorial groups at the end of an integrated course, where PBL is the main strategy of learning. The validity of the internal structure of the questionnaire was tested by confirmatory factor analysis using structural equation modeling assuming five different models. Predictive validity evidence of the questionnaire was studied by examining the correlations between students’ engagement and academic achievement.

Results

Confirmatory factor analysis indicates a good fit between the measurement and structural model of an 11-item questionnaire composed of a three-factor structure: behavioral engagement (3 items), emotional engagement (4 items), and cognitive engagement (4 items). Models in which the three latent factors were considered semi-independent provided the best fit. The construct reliabilities of behavioral, cognitive, and emotional factors were 0.82, 0.82, and 0.76, respectively. We failed however to find significant relationships between academic achievement and engagement.

Conclusions

We found a strong evidence to support the construct validity of a three-factor structure of student engagement in PBL tutorial questionnaire. Further studies are required to test the validity of this instrument in other educational settings. The predictive validity is another area needing further scrutiny.
Analysis of the Doctor of Public Health (DrPH) training and identity needs in the United States: a qualitative study
Authors: Park Chulwoo , Delgado Cindy
Published: November 2023

Background

The Doctor of Public Health (DrPH) is the highest attainable degree in the field of public health, specifically designed to prepare professionals to address complex public health challenges in practical settings. This study was designed to explore the importance of achieving a shared and uniform understanding of DrPH education, assess the optimal direction for DrPH training, and investigate the specific curriculum requirements by gathering insights from current DrPH students and alumni in the United States.

Methods

A total of 13 focus group discussions and two in-depth interviews (total participants: 50) were conducted through Zoom to see how DrPH students and alumni assessed their DrPH educational programs.

Results

Three overarching findings emerged from the analysis of focus group discussions and in-depth interviews. First, participants expressed a preference against a national DrPH board examination, but advocated for a standardized common core curriculum that extends across the entire nation. Second, the ideal direction for DrPH training was perceived to involve a practice-based approach, emphasizing the importance of multi-, inter-, and trans-disciplinary instruction delivered by faculty with practical experience. Last, there was a demand for a DrPH-specific unique curriculum encompassing areas such as mixed method analysis, leadership and management, applied communication, crisis and change management, proficiency in addressing contemporary topics, and tailored applied and integrative learning requirements specific to the DrPH program.

Conclusions

We explored a range of DrPH training and identity needs among 50 participants, comprised of students and alumni who directly benefit from DrPH education. By considering these inputs, individuals from institutions that offer the DrPH degree can further enhance the quality of public health practice training and make significant contributions to the overall advancement of the field of public health.
Real-world outcomes of concomitant antidepressant and statin use in primary care patients with depression: a population-based cohort study
Authors: De Giorgi Riccardo , De Crescenzo Franco , Cowen Philip J. , Harmer Catherine J. , Cipriani Andrea
Published: November 2023

Background

Antidepressants are licensed for use in depressive disorders, but non-response and poor adherence to treatment affect a considerable number of patients. Pre-clinical and clinical evidence suggest that statins can augment the effects of antidepressants. However, the acceptability and tolerability of combining statins with antidepressants are unclear, and their add-on efficacy has only been shown in small, short-term clinical trials. Observational data can provide complementary information about treatment effects on larger samples over longer follow-ups. In this study, we therefore assessed the real-world acceptability, tolerability, and efficacy of concomitant antidepressant and statin treatment in depression.

Methods

We conducted a population-based cohort study investigating QResearch primary care research database, which comprises the anonymised electronic healthcare records of 35 + million patients over 1574 English general practices. Patients aged 18–100 years, registered between January 1998 and August 2020, diagnosed with a new episode of depression, and commencing an antidepressant were included. Using a between-subject design, we identified two study groups: antidepressant + statin versus antidepressant-only prescriptions.

Outcomes of interest included the following: antidepressant treatment discontinuations due to any cause (acceptability) and due to any adverse event (tolerability) and effects on depressive symptoms (efficacy) measured as response, remission, and change in depression score on the Patient Health Questionnaire-9. All outcomes were assessed at 2, 6, and 12 months using multivariable regression analyses, adjusted for relevant confounders, to calculate adjusted odds ratios (aORs) or mean differences (aMDs) with 99% confidence intervals (99% CIs).

Results

Compared to antidepressant-only (N 626,335), antidepressant + statin (N 46,482) was associated with higher antidepressant treatment acceptability (aOR2months 0.88, 99% CI 0.85 to 0.91; aOR6months 0.81, 99% CI 0.79 to 0.84; aOR12months 0.78, 99% CI 0.75 to 0.81) and tolerability (aOR2months 0.92, 99% CI 0.87 to 0.98; aOR6months 0.94, 99% CI 0.89 to 0.99, though not long term aOR12 months 1.02, 99% CI 0.97 to 1.06). Efficacy did not differ between groups (range aOR2-12 months 1.00 and 1.02 for response and remission, range aOR2-12 months − 0.01 and − 0.02 for change in depression score).

Conclusions

On real-world data, there is a positive correlation between antidepressant treatment adherence and statin use, partly explained by fewer dropouts due to adverse events. The main limitation of our study is its observational design, which restricts the potential to make causal inferences.
Effect of fluralaner on the biology, survival, and reproductive fitness of the neotropical malaria vector Anopheles aquasalis
Authors: Alcântara João Arthur , de Araújo Francys Sayara Andrade , da Costa Paz Andréia , Alencar Rodrigo Maciel , de Albuquerque Caldas Berta Yoná , Godoy Raquel Soares Maia , Lacerda Marcus Vinicius Guimarães , de Melo Gisely Cardoso , Monteiro Wuelton Marcelo , de Souza Sampaio Vanderson , Secundino Nágila Francinete Costa , Duarte Ana Paula Marques , Santana Rosa Amélia Gonçalves , Pimenta Paulo Filemon Paolucci
Published: November 2023

Background

Reducing mosquito abundance or interfering with its ability to support the parasite cycle can help to interrupt malaria in areas of significant risk of malaria transmission. Fluralaner is a safe and effective drug for veterinary use indicated for the treatment against fleas and ticks which acts as an antagonist of chloride ion channels mediated by γ-aminobutyric acid (GABA), preventing the entry of these ions into the postsynaptic neuron, leading to hyperexcitability of the postsynaptic neuron of the central nervous system of arthropods. Fluralaner demonstrated insecticidal activity against different insect species.

Methods

The study aimed to evaluate the effects of fluralaner on the biology, survival, and reproductive fitness of Anopheles aquasalis. The following lethal concentrations (LC) were determined for An. aquasalis: LC5 = 0.511 µM; LC25 = 1.625 µM; LC50 = 3.237 µM.

Results

A significant decrease (P < 0.001) was evident in the number of eggs, larvae, and pupae in the group exposed to a sublethal dose of fluralaner when compared to a control group (without the drug). Using blood from dogs after administration of fluralaner, it was observed that the drug causes 100% mortality in An. aquasalis in less than 24 h after feeding; this effect remains even after 90 days in all samples.

Discussion

Fluralaner showed the same result for up to 60 days, and after that, there was a slight reduction in its effect, evidenced by a decrease in the percentage of dead females; however, still significant when compared to the control group.

Conclusion

Fluralaner affects the biology and reduction of survival in An. aquasalis in a lasting and prolonged period, and its fecundity with lower dosages, is a strong candidate for controlling disease vectors.
Systematic analysis of various RNA transcripts and construction of biological regulatory networks at the post-transcriptional level for chronic obstructive pulmonary disease
Authors: Li Beibei , Zhang Jiajun , Dong Hui , Feng Xueyan , Yu Liang , Zhu Jinyuan , Zhang Jin
Published: November 2023

Background

Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs.

Methods

All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels.

Results

Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD.

Conclusions

We identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.
Effects of high-intensity gait training with and without soft robotic exosuits in people post-stroke: a development-of-concept pilot crossover trial
Authors: Porciuncula Franchino , Arumukhom Revi Dheepak , Baker Teresa C. , Sloutsky Regina , Walsh Conor J. , Ellis Terry D. , Awad Louis N.
Published: November 2023

Introduction

High-intensity gait training is widely recognized as an effective rehabilitation approach after stroke. Soft robotic exosuits that enhance post-stroke gait mechanics have the potential to improve the rehabilitative outcomes achieved by high-intensity gait training. The objective of this development-of-concept pilot crossover study was to evaluate the outcomes achieved by high-intensity gait training with versus without soft robotic exosuits.

Methods

In this 2-arm pilot crossover study, four individuals post-stroke completed twelve visits of speed-based, high-intensity gait training: six consecutive visits of Robotic Exosuit Augmented Locomotion (REAL) gait training and six consecutive visits without the exosuit (CONTROL). The intervention arms were counterbalanced across study participants and separated by 6 + weeks of washout. Walking function was evaluated before and after each intervention using 6-minute walk test (6MWT) distance and 10-m walk test (10mWT) speed. Moreover, 10mWT speeds were evaluated before each training visit, with the time-course of change in walking speed computed for each intervention arm. For each participant, changes in each outcome were compared to minimal clinically-important difference (MCID) thresholds. Secondary analyses focused on changes in propulsion mechanics and associated biomechanical metrics.

Results

Large between-group effects were observed for 6MWT distance (d = 1.41) and 10mWT speed (d = 1.14). REAL gait training resulted in an average pre-post change of 68 ± 27 m (p = 0.015) in 6MWT distance, compared to a pre-post change of 30 ± 16 m (p = 0.035) after CONTROL gait training. Similarly, REAL training resulted in a pre-post change of 0.08 ± 0.03 m/s (p = 0.012) in 10mWT speed, compared to a pre-post change of 0.01 ± 06 m/s (p = 0.76) after CONTROL. For both outcomes, 3 of 4 (75%) study participants surpassed MCIDs after REAL training, whereas 1 of 4 (25%) surpassed MCIDs after CONTROL training. Across the training visits, REAL training resulted in a 1.67 faster rate of improvement in walking speed. Similar patterns of improvement were observed for the secondary gait biomechanical outcomes, with REAL training resulting in significantly improved paretic propulsion for 3 of 4 study participants (p < 0.05) compared to 1 of 4 after CONTROL.

Conclusion

Soft robotic exosuits have the potential to enhance the rehabilitative outcomes produced by high-intensity gait training after stroke. Findings of this development-of-concept pilot crossover trial motivate continued development and study of the REAL gait training program.
Top-level leaders and implementation strategies to support organizational diversity, equity, inclusion, and belonging (DEIB) interventions: a qualitative study of top-level DEIB leaders in healthcare organizations
Authors: Hogan Tory H. , O’Rourke Brian P. , Weeks Eddie , Silvera Geoffrey A. , Choi Seongwon
Published: November 2023

Background

The Black Lives Matter movement and COVID-19 pandemic motivated the wide-scale adoption of diversity, equity, inclusion, and belonging (DEIB) initiatives within healthcare organizations and the creation of DEIB top-level leader positions. The next step is to understand how these leaders contribute to the implementation of DEIB interventions, a task with notable salience due to not only the historical difficulties associated with DEIB strategy execution, but also the substantial evidence that leadership plays a significant role in implementation processes. Therefore, the objective of this qualitative study is to understand the role of top-level DEIB leaders in the implementation of healthcare organizational DEIB interventions.

Methods

A qualitative research approach which used an in-depth semi-structured interview approach was employed. We conducted thirty-one 60–90-min semi-structured interviews with DEIB top-level leaders between February 2022 and October 2022 over Zoom. An iterative coding process was used to identify the key implementation strategies and activities of DEIB top-level leaders.

Results

Interviewees were mostly Black, majority female, and mostly heterosexual and had a variety of educational backgrounds. We identified the DEIB top-level leader as the DEIB strategy implementation champion. These leaders drive five DEIB implementation strategies: (1) People, (2) Health Equity, (3) Monitoring and Feedback, (4) Operational Planning and Communication, and (5) External Partners. Within these, we identified 19 significant activities that describe the unique implementation strategies supported by the DEIB top-level leaders.

Conclusions

To move toward sustained commitment to DEIB, the organization must focus on not only establishing DEIB interventions, but on their successful implementation. Our findings help explicate the implementation activities that drive the DEIB initiatives of healthcare organizations and the role of DEIB leaders. Our work can help healthcare organizations systematically identify how to support the success of DEIB organizational interventions.
The association of osteoprotegerin and RANKL with osteoporosis: a systematic review with meta-analysis
Authors: Chi Guanghao , Qiu Longshun , Ma Jian , Wu Wei , Zhang Yuxin
Published: November 2023

Objectives

The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis.

Methods

The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I2 values. Subgroup analysis was performed based on different bone turnover.

Results

A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD =  − 1.17; 95% CI − 1.77 to 0.57; P value < 0.01) in subanalysis. Furthermore, the OPG/RANKL ratio was significant lower in the osteoporosis group than in the control group (SMD =  − 0.29; 95% CI − 0.57 to − 0.02; P value < 0.05), and the statistical heterogeneity was very low (Chi2 = 0.20, P = 0.66, I2 = 0%).

Conclusions

Our meta-analysis study supported OPG and RANKL were important modulatory factors of bone formation and resorption in bone turnover, respectively. Although the serum level of both OPG and RANKL were not associated with osteoporosis, but the OPG/RANKL ratio was associated with osteoporosis. In future, standardizing the test method and unit was good to clinical application.
Investigation of androgen receptor CAG repeats length in polycystic ovary syndrome diagnosed using the new international evidence-based guideline
Authors: Yan Xueqi , Gao Xueying , Shang Qian , Yang Ziyi , Wang Yuteng , Liu Li , Liu Wei , Liu Dan , Cheng Fang , Zhao Shigang , Zhao Han , Zhao Junli , Chen Zi-Jiang
Published: November 2023

Background

To study whether CAG repeat polymorphism of androgen receptor (AR) contributes to the risk of polycystic ovarian morphology (PCOM) with antral follicle count (AFC) ≥ 20 in the context of new international guideline of polycystic ovary syndrome (PCOS).

Methods

Blood of 109 PCOS cases and 61 controls were collected for the measurement of AR CAG repeats length by sequencing. The mean number and frequency distribution of CAG repeats length were observed. Detailed analysis was conducted by dividing PCOS cases into low AFC group (L-AFC, AFC < 20) and high AFC group (H-AFC, AFC ≥ 20) according to the new international evidence-based guideline.

Results

The portion of individuals with lower CAG repeats length in H-AFC group was significantly larger than those with higher CAG repeats length. Logistic model revealed individuals with lower CAG length tended to develop H-AFC.

Conclusion

Lower CAG repeats length in the AR gene of PCOS cases increases risk of PCOM.
Upregulation of RSPO3 via targeted promoter DNA demethylation inhibits the progression of cholangiocarcinoma
Authors: Wu Guanhua , Wang Da , Xiong Fei , Liu Wenzheng , Wang Qi , Chen Junsheng , Wang Bing , Chen Yongjun
Published: November 2023

Background

Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research.

Results

Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression.

Conclusions

Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA.
Subject classification and cross-time prediction based on functional connectivity and white matter microstructure features in a rat model of Alzheimer’s using machine learning
Authors: Diao Yujian , Lanz Bernard , Jelescu Ileana Ozana
Published: November 2023

Background

The pathological process of Alzheimer’s disease (AD) typically takes decades from onset to clinical symptoms. Early brain changes in AD include MRI-measurable features such as altered functional connectivity (FC) and white matter degeneration. The ability of these features to discriminate between subjects without a diagnosis, or their prognostic value, is however not established.

Methods

The main trigger mechanism of AD is still debated, although impaired brain glucose metabolism is taking an increasingly central role. Here, we used a rat model of sporadic AD, based on impaired brain glucose metabolism induced by an intracerebroventricular injection of streptozotocin (STZ). We characterized alterations in FC and white matter microstructure longitudinally using functional and diffusion MRI. Those MRI-derived measures were used to classify STZ from control rats using machine learning, and the importance of each individual measure was quantified using explainable artificial intelligence methods.

Results

Overall, combining all the FC and white matter metrics in an ensemble way was the best strategy to discriminate STZ rats, with a consistent accuracy over 0.85. However, the best accuracy early on was achieved using white matter microstructure features, and later on using FC. This suggests that consistent damage in white matter in the STZ group might precede FC. For cross-timepoint prediction, microstructure features also had the highest performance while, in contrast, that of FC was reduced by its dynamic pattern which shifted from early hyperconnectivity to late hypoconnectivity.

Conclusions

Our study highlights the MRI-derived measures that best discriminate STZ vs control rats early in the course of the disease, with potential translation to humans.
Management of traumatic cervical epidural hematoma in patients on Xa-inhibitors: a case report and review of the literature
Authors: Dang Robert , Issagholian Leo , Schmidt Tegan , Raoufi Pasha , Neeki Cameron C. , Neeki Michael M.
Published: November 2023

Background

Cervical epidural hematoma (CEH) is defined as a collection of blood in the suprameningeal space. Mechanisms of this rare pathology include spontaneous, postsurgical, and traumatic as the main subtypes. This unique case of traumatic CEH represents an even smaller subset of these cases. Management varies by symptom presentation, mechanism of injury, and other contraindications.

Case presentation

This case presents a 32 year old African American female on an oral anticoagulant sustaining traumatic cervical hematoma after a motor vehicle collision. Patient complained of neck, abdominal, and back pain. Imaging revealed a cervical spinal hematoma at the level of C3–C6. This case discusses the management of CEH for the general population and in the setting of anticoagulation.

Conclusion

Management of each case of CEH must be carefully considered and tailored based on their symptom presentation and progression of disease. As the use of anticoagulation including factor Xa inhibitors becomes more prevalent, there is greater need to understand the detailed pathophysiological aspect of the injuries. Targeted reversal agents such as Prothrombin Concentrate can be used for conservative treatment. Adjunct testing such as thromboelastogram can be used to help guide management.