bluuebunny/crossref_metadata_2025 huggingface dataset:
Origanum majorana L. protects against neuroinflammation-mediated cognitive impairment: a phyto-pharmacological study
Authors: Wagdy Reham , Abdel-Kader Reham M. , El-Khatib Ahmed H. , Linscheid Michael W. , Handoussa Heba , Hamdi Nabila
Published: May 2023

Background

Neuroinflammation and oxidative stress are critical players in the pathogenesis of numerous neurodegenerative diseases, such as Alzheimer’s disease (AD) which is responsible for most cases of dementia in the elderly. With the lack of curative treatments, natural phenolics are potential candidates to delay the onset and progression of such age-related disorders due to their potent antioxidant and anti-inflammatory effects. This study aims at assessing the phytochemical characteristics of Origanum majorana L. (OM) hydroalcohol extract and its neuroprotective activities in a murine neuroinflammatory model.

Methods

OM phytochemical analysis was done by HPLC/PDA/ESI-MSn. Oxidative stress was induced in vitro by hydrogen peroxide and cell viability was measured using WST-1 assay. Swiss albino mice were injected intraperitoneally with OM extract at a dose of 100 mg/kg for 12 days and with 250 μg/kg LPS daily starting from day 6 to induce neuroinflammation. Cognitive functions were assessed by novel object recognition and Y-maze behavioral tests. Hematoxylin and eosin staining was used to assess the degree of neurodegeneration in the brain. Reactive astrogliosis and inflammation were assessed by immunohistochemistry using GFAP and COX-2 antibodies, respectively.

Results

OM is rich in phenolics, with rosmarinic acid and its derivatives being major constituents. OM extract and rosmarinic acid significantly protected microglial cells against oxidative stress-induced cell death (p < 0.001). OM protected against the LPS-induced alteration of recognition and spatial memory in mice (p < 0.001) and (p < 0.05), respectively. Mice that received OM extract prior to the induction of neuroinflammation showed comparable histology to control brains, with no overt neurodegeneration. Furthermore, OM pre-treatment decreased the immunohistochemistry profiler score of GFAP from positive to low positive and COX-2 from low positive to negative in the brain tissue, compared to the LPS group.

Conclusion

These findings highlight the potential preventive effects of OM phenolics against neuroinflammation and pave the way toward drug discovery and development for neurodegenerative disorders.
Measurement of student engagement in health professions education: a review of literature
Authors: Kassab Salah Eldin , Al-Eraky Mohamed , El-Sayed Walid , Hamdy Hossam , Schmidt Henk
Published: May 2023

Student engagement is a complex multidimensional construct that has attained great interest in health professions education (HPE). Definition and conceptualization of student engagement is an important step that should drive the development of the instruments for its measurement. We have recently proposed a comprehensive framework for student engagement in HPE with a definition of engagement as student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. The dimensions of student engagement in this framework included the cognitive, affective, behavioral, agentic, and socio-cultural. Guided by the student engagement framework, this non-systematic review aims to identify, critically appraise, and summarize the existing methods for measuring student engagement in HPE. Extrapolating from higher education literature, we attempted to link the theoretical perspectives of student engagement with the published methods of its measurement in HPE context. In addition, we have described the different methods of measuring student engagement including self-report surveys, real time measures, direct observation, interviews/focus groups, and the use of multiple instruments. The span of engagement dimensions measured by self-report surveys ranges from one to five dimensions. However, measurement of agentic and sociocultural dimensions of engagement in HPE is still limited and further research is required. We have also reflected on the existing methods of measuring engagement of students as active partners in HPE. The review also describes the advantages, limitations, and psychometric properties of each method for measuring student engagement. We ended the review with a guiding conclusion on how to develop and select an instrument for measuring student engagement in HPE. Finally, we addressed the gaps in the literature about measuring engagement of HPE students and future research plans.
The knock-on effects of COVID-19 pandemic on the supply and availability of generic medicines in Ethiopia: mixed methods study
Authors: Mekonnen Zeleke , Melaku Tsegaye , Tucho Gudina Terefe , Mecha Mohammed , Årdal Christine , Jahre Marianne
Published: May 2023

Background

COVID-19 pandemic posed a major impact on the availability and affordability of essential medicines. This study aimed to assess the knock-on effects of the COVID-19 pandemic on the supply availability of non-communicable chronic disease (NCD) medicines and paracetamol products in Ethiopia.

Methods

A mixed methods study was conducted to assess the supply and availability of twenty-four NCD drugs and four paracetamol products listed on the national essential medicines list for hospitals. Data were collected from twenty-six hospitals located in seven zones of Oromia region in the southwestern part of Ethiopia. We extracted data on drug availability, cost and stock out for these drugs between May 2019 and December 2020. The quantitative data were entered into Microsoft Excel and exported to statistical package software for social science (SPSS) version 22 (IBM Corporation, Armonk, NY, USA) software for analysis.

Results

The overall mean availability of selected basket medicines was 63.4% (range 16.7% to 80.3%) during the pre-COVID-19 time. It was 46.3% (range 2.8% to 88.7) during the pandemic. There was a relative increase in the availability of two paracetamol products [paracetamol 500 mg tablet (67.5% versus 88.7%) and suppository (74.5% versus 88%)] during the pandemic. The average monthly orders fill rates for the selected products range from 43 to 85%. Pre-COVID-19, the average order fill rate was greater or equal to 70%. However, immediately after the COVID-19 case notification, the percentage of order(s) filled correctly in items and quantities began decreasing. Political instability, shortage of trained human resources, currency inflation, and limited drug financing were considered as the major challenges to medicine supply.

Conclusion

The overall stock out situation in the study area has worsened during COVID-19 compared to pre-COVID-19 time. None of the surveyed chronic disease basket medicines met the ideal availability benchmark of 80% in health facilities. However, availability of paracetamol 500 mg tablet surprisingly improved during the pandemic. A range of policy frameworks and options targeting inevitable outbreaks should exist to enable governments to ensure that medicines for chronic diseases are consistently available and affordable.
Identification of genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous cell carcinoma
Authors: Liu Shaokun , Wang Shuning , Wang Zhenlin
Published: May 2023

Objective

To identify the genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous carcinoma (HNSC).

Materials and methods

RNA sequencing data and clinical characteristics of HNSC patients were procured from The Cancer Genome Atlas (TCGA) database. Lipid metabolism-related genes were collected from KEGG and MSigDB databases. Immune cells and immune-related genes were obtained from the TISIDB database. The differentially expressed genes (DEGs) in HNSC were identified and weighted correlation network analysis (WGCNA) was performed to identify the significant gene modules. Lasso regression analysis was performed to identify hub genes. The differential gene expression pattern, diagnostic values, relationships with clinical features, prognostic values, relationships with tumor mutation burden (TMB), and signaling pathways involved, were each investigated.

Results

One thousand six hundred sixty-eight DEGs were identified as dysregulated between HNSC tumor samples and healthy control head and neck samples. WGCNA analysis and Lasso regression analysis identified 8 hub genes, including 3 immune-related genes (PLA2G2D, TNFAIP8L2 and CYP27A1) and 5 lipid metabolism-related genes (FOXP3, IL21R, ITGAL, TRAF1 and WIPF1). Except CYP27A1, the other hub genes were upregulated in HNSC as compared with healthy control samples, and a low expression of these hub genes indicated a higher risk of death in HNSC. Except PLA2G2D, all other hub genes were significantly and negatively related with TMB in HNSC. The hub genes were implicated in several immune-related signaling pathways including T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity.

Conclusion

Three immune genes (PLA2G2D, TNFAIP8L2, and CYP27A1) and immune-related pathways (T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity) were predicted to play significant roles in the lipid metabolism-mediated tumor immunity in HNSC.
Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study
Authors: Vultaggio Alessandra , Aliani Maria , Altieri Elena , Bracciale Pietro , Brussino Luisa , Caiaffa Maria Filomena , Cameli Paolo , Canonica Giorgio Walter , Caruso Cristiano , Centanni Stefano , D’Amato Maria , De Michele Fausto , Del Giacco Stefano , Di Marco Fabiano , Menzella Francesco , Pelaia Girolamo , Rogliani Paola , Romagnoli Micaela , Schino Pietro , Senna Gianenrico , Benci Marco , Boarino Silvia , Schroeder Jan Walter
Published: May 2023

Background

The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks.

Methods

ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only.

Results

Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430–890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: − 94.9%; severe AER: − 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: − 95.9%; severe AER: − 97.5%) and bio-experienced patients (any AER: − 92.4%; severe AER: − 94.0%).

Conclusions

Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients’ eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results.

Trial registration: ClinicalTrials.gov Identifier: NCT04272463.
The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer
Authors: Entrialgo-Cadierno Rodrigo , Cueto-Ureña Cristina , Welch Connor , Feliu Iker , Macaya Irati , Vera Laura , Morales Xabier , Michelina Sandra Vietti , Scaparone Pietro , Lopez Ines , Darbo Elodie , Erice Oihane , Vallejo Adrian , Moreno Haritz , Goñi-Salaverri Ainhoa , Lara-Astiaso David , Halberg Nils , Cortes-Dominguez Ivan , Guruceaga Elizabeth , Ambrogio Chiara , Lecanda Fernando , Vicent Silve
Published: May 2023

Background

The discovery of functionally relevant KRAS effectors in lung and pancreatic ductal adenocarcinoma (LUAD and PDAC) may yield novel molecular targets or mechanisms amenable to inhibition strategies. Phospholipids availability has been appreciated as a mechanism to modulate KRAS oncogenic potential. Thus, phospholipid transporters may play a functional role in KRAS-driven oncogenesis. Here, we identified and systematically studied the phospholipid transporter PITPNC1 and its controlled network in LUAD and PDAC.

Methods

Genetic modulation of KRAS expression as well as pharmacological inhibition of canonical effectors was completed. PITPNC1 genetic depletion was performed in in vitro and in vivo LUAD and PDAC models. PITPNC1-deficient cells were RNA sequenced, and Gene Ontology and enrichment analyses were applied to the output data. Protein-based biochemical and subcellular localization assays were run to investigate PITPNC1-regulated pathways. A drug repurposing approach was used to predict surrogate PITPNC1 inhibitors that were tested in combination with KRASG12C inhibitors in 2D, 3D, and in vivo models.

Results

PITPNC1 was increased in human LUAD and PDAC, and associated with poor patients’ survival. PITPNC1 was regulated by KRAS through MEK1/2 and JNK1/2. Functional experiments showed PITPNC1 requirement for cell proliferation, cell cycle progression and tumour growth. Furthermore, PITPNC1 overexpression enhanced lung colonization and liver metastasis. PITPNC1 regulated a transcriptional signature which highly overlapped with that of KRAS, and controlled mTOR localization via enhanced MYC protein stability to prevent autophagy. JAK2 inhibitors were predicted as putative PITPNC1 inhibitors with antiproliferative effect and their combination with KRASG12C inhibitors elicited a substantial anti-tumour effect in LUAD and PDAC.

Conclusions

Our data highlight the functional and clinical relevance of PITPNC1 in LUAD and PDAC. Moreover, PITPNC1 constitutes a new mechanism linking KRAS to MYC, and controls a druggable transcriptional network for combinatorial treatments.

Graphical Abstract
Serum lipidomics reveals phosphatidylethanolamine and phosphatidylcholine disorders in patients with myocardial infarction and post-myocardial infarction-heart failure
Authors: Rong Jidong , He Tianmu , Zhang Jianyong , Bai Zhixun , Shi Bei
Published: May 2023

Background

Myocardial infarction (MI) and post-MI-heart failure (pMIHF) are a major cause of death worldwide, however, the underlying mechanisms of pMIHF from MI are not well understood. This study sought to characterize early lipid biomarkers for the development of pMIHF disease.

Methods

Serum samples from 18 MI and 24 pMIHF patients were collected from the Affiliated Hospital of Zunyi Medical University and analyzed using lipidomics with Ultra High Performance Liquid Chromatography and Q-Exactive High Resolution Mass Spectrometer. The serum samples were tested by the official partial least squares discriminant analysis (OPLS-DA) to find the differential expression of metabolites between the two groups. Furthermore, the metabolic biomarkers of pMIHF were screened using the subject operating characteristic (ROC) curve and correlation analysis.

Results

The average age of the 18 MI and 24 pMIHF participants was 57.83 ± 9.28 and 64.38 ± 10.89 years, respectively. The B-type natriuretic peptide (BNP) level was 328.5 ± 299.842 and 3535.96 ± 3025 pg/mL, total cholesterol(TC) was 5.59 ± 1.51 and 4.69 ± 1.13 mmol/L, and blood urea nitrogen (BUN) was 5.24 ± 2.15 and 7.20 ± 3.49 mmol/L, respectively. In addition, 88 lipids, including 76 (86.36%) down-regulated lipids, were identified between the patients with MI and pMIHF. ROC analysis showed that phosphatidylethanolamine (PE) (12:1e_22:0) (area under the curve [AUC] = 0.9306) and phosphatidylcholine (PC) (22:4_14:1) (AUC = 0.8380) could be potential biomarkers for the development of pMIHF. Correlation analysis showed that PE (12:1e_22:0) was inversely correlated with BNP and BUN, but positively correlated with TC. In contrast, PC (22:4_14:1) was positively associated with both BNP and BUN, and was negatively associated with TC.

Conclusions

Several lipid biomarkers were identified that could potentially be used to predict and diagnose patients with pMIHF. PE (12:1e_22:0) and PC (22:4_14:1) could sufficiently differentiate between patients with MI and pMIHF.
Noninvasive right ventricular work in patients with atrial septal defects: a proof-of-concept study
Authors: Wu Jian , Huang Xinyi , Chen Weibin , Tang Yiruo , Chen Xu , Wang Xinyu , Jing Bo , Sun Yuanyuan , Huang Kunhui , Gao Qiumei , Liu Xueming , Su Maolong
Published: May 2023

Background

Noninvasive right ventricular (RV) myocardial work (RVMW) determined by echocardiography is a novel indicator used to estimate RV systolic function. To date, the feasibility of using RVMW has not been verified in assessing RV function in patients with atrial septal defect (ASD).

Methods

Noninvasive RVMW was analysed in 29 ASD patients (median age, 49 years; 21% male) and 29 age- and sex-matched individuals without cardiovascular disease. The ASD patients underwent echocardiography and right heart catheterization (RHC) within 24 h.

Results

The RV global work index (RVGWI), RV global constructive work (RVGCW), and RV global wasted work (RVGWW) were significantly higher in the ASD patients than in the controls, while there was no significant difference in RV global work efficiency (RVGWE). RV global longitudinal strain (RV GLS), RVGWI, RVGCW, and RVGWW demonstrated significant correlations with RHC-derived stroke volume (SV) and SV index. The RVGWI (area under receiver operating characteristic curve [AUC] = 0.895), RVGCW (AUC = 0.922), and RVGWW (AUC = 0.870) could be considered good predictors of ASD and were superior to RV GLS (AUC = 0.656).

Conclusion

The RVGWI, RVGCW, and RVGWW could be used to assess RV systolic function and are correlated with RHC-derived SV and SV index in patients with ASD.

Graphical Abstract
CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach
Authors: Zhang Xiaofei , Hu Qin , He Xuesong , Cui Xinyue , Liang Zhaoyuan , Wang Li , Deng Xiongwei , Zhang Ze , Sheng Wang , Han Xiaodong D.
Published: May 2023

Background

Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG.

Results

In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3+CD8+ murine T cells.

Conclusion

Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine.
Quality of routine health data at the onset of the COVID-19 pandemic in Ethiopia, Haiti, Laos, Nepal, and South Africa
Authors: Ayele Wondimu , Gage Anna , Kapoor Neena R. , Kassahun Gelaw Solomon , Hensman Dilipkumar , Derseh Mebratie Anagaw , Nega Adiam , Asai Daisuke , Molla Gebeyaw , Mehata Suresh , Mthethwa Londiwe , Mfeka-Nkabinde Nompumelelo Gloria , Joseph Jean Paul , Pierre Daniella Myriam , Thermidor Roody , Arsenault Catherine
Published: May 2023

Background

During the COVID-19 pandemic, governments and researchers have used routine health data to estimate potential declines in the delivery and uptake of essential health services. This research relies on the data being high quality and, crucially, on the data quality not changing because of the pandemic. In this paper, we investigated those assumptions and assessed data quality before and during COVID-19.

Methods

We obtained routine health data from the DHIS2 platforms in Ethiopia, Haiti, Lao People’s Democratic Republic, Nepal, and South Africa (KwaZulu-Natal province) for a range of 40 indicators on essential health services and institutional deaths. We extracted data over 24 months (January 2019–December 2020) including pre-pandemic data and the first 9 months of the pandemic. We assessed four dimensions of data quality: reporting completeness, presence of outliers, internal consistency, and external consistency.

Results

We found high reporting completeness across countries and services and few declines in reporting at the onset of the pandemic. Positive outliers represented fewer than 1% of facility-month observations across services. Assessment of internal consistency across vaccine indicators found similar reporting of vaccines in all countries. Comparing cesarean section rates in the HMIS to those from population-representative surveys, we found high external consistency in all countries analyzed.

Conclusions

While efforts remain to improve the quality of these data, our results show that several indicators in the HMIS can be reliably used to monitor service provision over time in these five countries.
Study on wild medicinal plant resources and their applied ethnology in multiethnic areas of the Gansu–Ningxia–Inner Mongolia intersection zone
Authors: Xie Jian , Luo Chaoqun , Yang Xingwu , Ren Yan , Zhang Xingsheng , Chen Haoran , Zhao Yongxia , Liu Sha , Wu Faming
Published: May 2023

Introduction

This study conducted an ethnobotanical survey of wild medicinal plants in the multi-ethnic areas of Gansu–Ningxia–Inner Mongolia intersection zone. Traditional knowledge of medicinal plant use in the region was compiled to identify important medicinal plants currently used for treating relevant diseases and to determine species with potential for development.

Methods

Key informant interviews, semi-structured interviews, participatory rural appraisal methods, and ethnobotanical quantitative evaluation were used to investigate and study the traditional knowledge of local residents' use of wild medicinal plants in the region. The relative importance of the referenced plants was assessed, as well as the prominent species widely used in medicinal applications.

Results

The study found that the region has a total of 204 wild medicinal plant resources, belonging to 149 genera of 51 families. Among these resources, a total of 50 commonly used plants were identified (44 of which were herbs, some of which were multi-origin), belonging to 27 families, with the most species found in the Asteraceae family, with 11 species. These herbs are mainly used for preventing and treating colds and nourishing health, followed by treatment of fever, stomach problems, and bleeding. The most frequently used medicinal plant in the region is “Ai”, which includes Artemisia argyi Lévl. et Van. and Artemisia kanashiroi Kitam. All respondents provided information about the use of this medicinal plant to varying degrees, followed by Artemisia annua Linn., Ephedra sinica Stapf, Taraxacum mongolicum Hand.-Mazz., Sonchus arvensis Linn., Artemisia capillaris Thunb., among others.

Conclusion

Our investigation gained a wealth of traditional knowledge about the use of wild herbs, using wild herbs, which plays an important role in the lives of local residents. Especially, the herbs and application methods used for treating colds, bleeding, and stomach problems are worthy of further research and development.
Study protocol for a multicenter, multinational, observational registry of epidemiology, treatment and outcome of patients with Robin sequence
Authors: Oechsle Anna-Lisa , Wiechers Cornelia , Abadie Veronique , Abel Francois , Breugem Corstiaan , Poets Christian F.
Published: May 2023

Background

Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis and upper airway obstruction. Diagnosis and treatment are characterized by heterogeneity, resulting in a lack of uniformly collected data.

Methods

We have set up a prospective, observational, multicenter, multinational registry aimed at obtaining routine clinical data from RS patients receiving different treatment approaches and enabling an assessment of outcomes obtained through different therapeutic approaches. Patient enrolment has started in January 2022. Disease characteristics, adverse events and complications depending on the different diagnostic and treatment approaches and their effects on neurocognition, growth, speech development and hearing outcome are evaluated using routine clinical data. In addition to characterizing the patient population and comparing outcomes achieved with different treatment approaches, the registry will evolve to focus on endpoints such as quality of life and long-term developmental status.

Discussion

This registry will provide data on different treatment approaches collected during routine care with diverse framework conditions and will allow assessing diagnostic and therapeutic outcomes of children with RS. These data, urgently demanded by the scientific community, may contribute to refining and personalizing existing therapeutic approaches and increase knowledge about the long-term outcome of children born with this rare condition.

Trial registration

DRKS00025365.
Effectiveness of oral famotidine in reducing the hematologic complications of radiotherapy in patients with esophageal and cardia cancers: a randomized controlled trial
Authors: Rostami Mina , Yelghi Omid , Moghaddam Zhaleh Karimi , Zeraatchi Alireza , Rezaeejam Hamed , Sadeghi Alireza
Published: May 2023

Background

Chemoradiotherapy complications has always been of great concern to both clinicians and patients during the course of treatment. The purpose of the present study was to examine the effectiveness of oral famotidine on the reduction of hematologic complications of patients with esophageal and gastric cardia cancers undergoing radiotherapy.

Methods

A single-blind controlled trial was conducted on 60 patients with esophageal and cardia cancers, who were undergoing chemoradiotherapy. Patients were randomly assigned to 2 groups with 30 patients to receive either 40 mg of oral famotidine (daily and 4 h before each session) or placebo. Complete blood count with differential, platelet counts, and hemoglobin levels were obtained weekly during treatment. The main outcome variables were lymphocytopenia, granulocytopenia, thrombocytopenia, and anemia.

Results

The findings indicated a significant effect of famotidine on reduction of thrombocytopenia among intervention group compared to control group (P < 0.0001). Even so, the effect of intervention was not significant for other outcome variables (All, P ≥ 0.05). The lymphocyte (P = 0.007) and platelet (P = 0.004) counts were also significantly greater in famotidine group in comparison with placebo group at the end of the study.

Conclusion

As evidenced by the findings of the current study, famotidine might be recommended as an effective radioprotective agent among patients with esophageal and gastric cardia cancers to prevent Leukocyte and platelet reduction to some extent.

Trial registration This study was prospectively registered at irct.ir (Iranian Registry of Clinical Trials) with the code IRCT20170728035349N1, 2020-08-19.
Development of machine learning models aiming at knee osteoarthritis diagnosing: an MRI radiomics analysis
Authors: Cui Tingrun , Liu Ruilong , Jing Yang , Fu Jun , Chen Jiying
Published: May 2023

Background

To develop and assess the performance of machine learning (ML) models based on magnetic resonance imaging (MRI) radiomics analysis for knee osteoarthritis (KOA) diagnosis.

Methods

This retrospective study analysed 148 consecutive patients (72 with KOA and 76 without) with available MRI image data, where radiomics features in cartilage portions were extracted and then filtered. Intraclass correlation coefficient (ICC) was calculated to quantify the reproducibility of features, and a threshold of 0.8 was set. The training and validation cohorts consisted of 117 and 31 cases, respectively. Least absolute shrinkage and selection operator (LASSO) regression method was employed for feature selection. The ML classifiers were logistic regression (LR), K-nearest neighbour (KNN) and support vector machine (SVM). In each algorithm, ten models derived from all available planes of three joint compartments and their various combinations were, respectively, constructed for comparative analysis. The performance of classifiers was mainly evaluated and compared by receiver operating characteristic (ROC) analysis.

Results

All models achieved satisfying performances, especially the Final model, where accuracy and area under ROC curve (AUC) of LR classifier were 0.968, 0.983 (0.957–1.000, 95% CI) in the validation cohort, and 0.940, 0.984 (0.969–0.995, 95% CI) in the training cohort, respectively.

Conclusion

The MRI radiomics analysis represented promising performance in noninvasive and preoperative KOA diagnosis, especially when considering all available planes of all three compartments of knee joints.
Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions
Authors: Yu Yi-xuan , Wang Shuo , Liu Zhe-ning , Zhang Xu , Hu Zi-xin , Dong Hui-jing , Lu Xing-yu , Zheng Jia-bin , Cui Hui-juan
Published: May 2023

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.
Estimating biomass and soil carbon change at the level of forest stands using repeated forest surveys assisted by airborne laser scanner data
Authors: Strîmbu Victor F. , Næsset Erik , Ørka Hans Ole , Liski Jari , Petersson Hans , Gobakken Terje
Published: May 2023

Background

Under the growing pressure to implement mitigation actions, the focus of forest management is shifting from a traditional resource centric view to incorporate more forest ecosystem services objectives such as carbon sequestration. Estimating the above-ground biomass in forests using airborne laser scanning (ALS) is now an operational practice in Northern Europe and is being adopted in many parts of the world. In the boreal forests, however, most of the carbon (85%) is stored in the soil organic (SO) matter. While this very important carbon pool is “invisible” to ALS, it is closely connected and feeds from the growing forest stocks. We propose an integrated methodology to estimate the changes in forest carbon pools at the level of forest stands by combining field measurements and ALS data.

Results

ALS-based models of dominant height, mean diameter, and biomass were fitted using the field observations and were used to predict mean tree biophysical properties across the entire study area (50 km2) which was in turn used to estimate the biomass carbon stocks and the litter production that feeds into the soil. For the soil carbon pool estimation, we used the Yasso15 model. The methodology was based on (1) approximating the initial soil carbon stocks using simulations; (2) predicting the annual litter input based on the predicted growing stocks in each cell; (3) predicting the soil carbon dynamics of the annual litter using the Yasso15 soil carbon model. The estimated total carbon change (standard errors in parenthesis) for the entire area was 0.741 (0.14) Mg ha−1 yr−1. The biomass carbon change was 0.405 (0.13) Mg ha−1 yr−1, the litter carbon change (e.g., deadwood and leaves) was 0.346 (0.027) Mg ha−1 yr−1, and the change in SO carbon was − 0.01 (0.003) Mg ha−1 yr−1.

Conclusions

Our results show that ALS data can be used indirectly through a chain of models to estimate soil carbon changes in addition to changes in biomass at the primary level of forest management, namely the forest stands. Having control of the errors contributed by each model, the stand-level uncertainty can be estimated under a model-based inferential approach.
The experience of living with Niemann–Pick type C: a patient and caregiver perspective
Authors: Golden Emma , van Gool Raquel , Cay Mariesa , Goodlett Benjamin , Cao Amanda , Al-Hertani Walla , Upadhyay Jaymin
Published: May 2023

Background

Niemann–Pick disease type C (NPC) is a rare inherited lysosomal storage disease typified by accumulation of cholesterol and other lipids in late endosomes/lysosomes, thereby resulting in a spectrum of neurological, psychiatric, and systemic symptoms (notably liver disease). Though it is well-known that NPC exacts a physical and emotional toll on both patients and caregivers, the burden of NPC can vary between patients, while the challenges of living with NPC can evolve over time (i.e., from time of diagnosis to the present day). To further grasp patient and caregiver perceptions and experiences with NPC, we carried out focus group discussions with pediatric and adult individuals with NPC (N = 19), with partial or full representation of the patient by their caregiver. Furthermore, we utilized our NPC focus group discussion to provide guidance on study design parameters and feasibility of prospective investigations aiming to characterize the central manifestations of NPC using neuroimaging, specifically, magnetic resonance imaging (MRI) methodology.

Results

Focus group discussions revealed that neurological signs, including declining cognition, memory loss, and psychiatric symptoms, as well as increasingly impaired mobility and motor function, are among the most pressing past and current concerns for patients and caregivers. Moreover, several participants also expressed concern over a loss of independence, social exclusion, and uncertainty for what the future holds. Caregivers described the challenges that participation in research poses, which included logistical difficulties mainly due to traveling with medical equipment and the need for sedation in a minority of patients when undergoing MRI.

Conclusions

The findings derived from focus group discussions highlight the outstanding challenges that NPC patients and their caregivers face daily, while also providing direction on the potential scope and feasibility of future studies focusing on the central phenotypes of NPC.
The first year of the COVID-19 pandemic in humanitarian settings: epidemiology, health service utilization, and health care seeking behavior in Bangui and surrounding areas, Central African Republic
Authors: Altare Chiara , Kostandova Natalya , Gankpe Gbètoho Fortuné , Nalimo Patricia , Almoustapha Abaradine Abdoul Azizi ,   IMPACT CAR Team, Bruneau Sophie , Antoine Caroline , Spiegel Paul B.
Published: May 2023

Background

Despite increasing evidence on COVID-19, few studies have been conducted in humanitarian settings and none have investigated the direct and indirect effects of the pandemic in the Central African Republic. We studied the COVID-19 epidemiology, health service utilization, and health care seeking behavior in the first year of the pandemic in Bangui and surrounding areas.

Methods

This mixed-methods study encompasses four components: descriptive epidemiological analysis of reported COVID-19 cases data; interrupted time series analysis of health service utilization using routine health service data; qualitative analysis of health care workers’ perceptions of how health services were affected; and health care seeking behavior of community members with a household survey and focus group discussions.

Results

The COVID-19 epidemiology in CAR aligns with that of most other countries with males representing most of the tested people and positive cases. Testing capacity was mainly concentrated in Bangui and skewed towards symptomatic cases, travelers, and certain professions. Test positivity was high, and many cases went undiagnosed. Decreases in outpatient department consultations, consultations for respiratory tract infections, and antenatal care were found in most study districts. Cumulative differences in districts ranged from − 46,000 outpatient department consultations in Begoua to + 7000 in Bangui 3; − 9337 respiratory tract infections consultations in Begoua to + 301 in Bangui 1; and from − 2895 antenatal care consultations in Bimbo to + 702 in Bangui 2. Consultations for suspected malaria showed mixed results while delivery of BCG vaccine doses increased. Fewer community members reported seeking care at the beginning of the pandemic compared to summer 2021, especially in urban areas. The fear of testing positive and complying with related restrictions were the main obstacles to seeking care.

Conclusions

A large underestimation of infections and decreased health care utilization characterized the first year of the COVID-19 pandemic in Bangui and surrounding area. Improved decentralized testing capacity and enhanced efforts to maintain health service utilization will be crucial for future epidemics. A better understanding of health care access is needed, which will require strengthening the national health information system to ensure reliable and complete data. Further research on how public health measures interact with security constraints is needed.
Improving access to early intervention for autism: findings from a proof-of-principle cascaded task-sharing naturalistic developmental behavioural intervention in South Africa
Authors: Rieder Amber D. , Viljoen Marisa , Seris Noleen , Shabalala Nokuthula , Ndlovu Minkateko , Turner Elizabeth L. , Simmons Ryan , de Vries Petrus J. , Franz Lauren
Published: May 2023

Background

Despite the high number of children living with neurodevelopmental disabilities in sub–Saharan Africa, access to early intervention is almost non-existent. It is therefore important to develop feasible, scalable early autism intervention that can be integrated into systems of care. While Naturalistic Developmental Behavioural Intervention (NDBI) has emerged as an evidence-based intervention approach, implementation gaps exist globally, and task-sharing approaches may address access gaps. In this South African proof-of-principle pilot study, we set out to answer two questions about a 12-session cascaded task-sharing NDBI—whether the approach could be delivered with fidelity, and whether we could identify signals of change in child and caregiver outcomes.

Methods

We utilized a single-arm pre-post design. Fidelity (non-specialists, caregivers), caregiver outcomes (stress, sense of competence), and child outcomes (developmental, adaptive) were measured at baseline (T1) and follow-up (T2). Ten caregiver-child dyads and four non-specialists participated. Pre-to-post summary statistics were presented alongside individual trajectories. Non-parametric Wilcoxon signed rank test for paired samples was used to compare group medians between T1 and T2.

Results

Caregiver implementation fidelity increased in 10/10 participants. Non-specialists demonstrated a significant increase in coaching fidelity (increases in 7/10 dyads). Significant gains were seen on two Griffiths-III subscales (Language/Communication—9/10 improved, Foundations of Learning—10/10 improved) and on the General Developmental Quotient (9/10 improved). Significant gains were also seen on two Vineland Adaptive Behaviour Scales (Third Edition) subscales (Communication—9/10 improved, Socialization—6/10 improved) and in the Adaptive Behaviour Standard Score (9/10 improved). Caregiver sense of competence improved in 7/10 caregivers and caregiver stress in 6/10 caregivers.

Conclusions

This proof-of-principle pilot study of the first cascaded task-sharing NDBI in Sub-Saharan Africa provided fidelity and intervention outcome data which supported the potential of such approaches in low-resource contexts. Larger studies are needed to expand on the evidence-base and answer questions on intervention effectiveness and implementation outcomes.
Interneuronal GluK1 kainate receptors control maturation of GABAergic transmission and network synchrony in the hippocampus
Authors: Ojanen Simo , Kuznetsova Tatiana , Kharybina Zoia , Voikar Vootele , Lauri Sari E. , Taira Tomi
Published: May 2023

Kainate type glutamate receptors (KARs) are strongly expressed in GABAergic interneurons and have the capability of modulating their functions via ionotropic and G-protein coupled mechanisms. GABAergic interneurons are critical for generation of coordinated network activity in both neonatal and adult brain, yet the role of interneuronal KARs in network synchronization remains unclear. Here, we show that GABAergic neurotransmission and spontaneous network activity is perturbed in the hippocampus of neonatal mice lacking GluK1 KARs selectively in GABAergic neurons. Endogenous activity of interneuronal GluK1 KARs maintains the frequency and duration of spontaneous neonatal network bursts and restrains their propagation through the hippocampal network. In adult male mice, the absence of GluK1 in GABAergic neurons led to stronger hippocampal gamma oscillations and enhanced theta-gamma cross frequency coupling, coinciding with faster spatial relearning in the Barnes maze. In females, loss of interneuronal GluK1 resulted in shorter sharp wave ripple oscillations and slightly impaired abilities in flexible sequencing task. In addition, ablation of interneuronal GluK1 resulted in lower general activity and novel object avoidance, while causing only minor anxiety phenotype. These data indicate a critical role for GluK1 containing KARs in GABAergic interneurons in regulation of physiological network dynamics in the hippocampus at different stages of development.
Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo
Authors: Liu Junmei , Zhang Ranran , Su Tong , Zhou Qianqian , Gao Lin , He Zongyue , Wang Xin , Zhao Jian , Xing Yuanxin , Sun Feifei , Cai Wenjie , Wang Xinpei , Han Jingying , Qin Ruixi , Désaubry Laurent , Han Bo , Chen Weiwen
Published: May 2023

Background

Castration-resistant prostate cancer (CRPC) is currently the main challenge for prostate cancer (PCa) treatment, and there is an urgent need to find novel therapeutic targets and drugs. Prohibitin (PHB1) is a multifunctional chaperone/scaffold protein that is upregulated in various cancers and plays a pro-cancer role. FL3 is a synthetic flavagline drug that inhibits cancer cell proliferation by targeting PHB1. However, the biological functions of PHB1 in CRPC and the effect of FL3 on CRPC cells remain to be explored.

Methods

Several public datasets were used to analyze the association between the expression level of PHB1 and PCa progression as well as outcome in PCa patients. The expression of PHB1 in human PCa specimens and PCa cell lines was examined by immunohistochemistry (IHC), qRT-PCR, and Western blot. The biological roles of PHB1 in castration resistance and underlying mechanisms were investigated by gain/loss-of-function analyses. Next, in vitro and in vivo experiments were conducted to investigate the anti-cancer effects of FL3 on CRPC cells as well as the underlying mechanisms.

Results

PHB1 expression was significantly upregulated in CRPC and was associated with poor prognosis. PHB1 promoted castration resistance of PCa cells under androgen deprivation condition. PHB1 is an androgen receptor (AR) suppressive gene, and androgen deprivation promoted the PHB1 expression and its nucleus-cytoplasmic translocation. FL3, alone or combined with the second-generation anti-androgen Enzalutamide (ENZ), suppressed CRPC cells especially ENZ-sensitive CRPC cells both in vitro and in vivo. Mechanically, we demonstrated that FL3 promoted trafficking of PHB1 from plasma membrane and mitochondria to nucleus, which in turn inhibited AR signaling as well as MAPK signaling, yet promoted apoptosis in CRPC cells.

Conclusion

Our data indicated that PHB1 is aberrantly upregulated in CRPC and is involved in castration resistance, as well as providing a novel rational approach for treating ENZ-sensitive CRPC.
Resuscitative transesophageal echocardiography in the emergency department: a single-centre case series
Authors: Kegel Fraser , Chenkin Jordan
Published: May 2023

Background

Transesophageal echocardiography (TEE) is an emerging tool that can aid emergency physicians in treating patients in cardiac arrest and undifferentiated shock. TEE can aid in diagnosis, resuscitation, identify cardiac rhythms, guide chest compression vectors, and shorten sonographic pulse checks. This study evaluated the proportion of patients who underwent a change in their resuscitation management as a result of emergency department resuscitative TEE.

Methods

This was a single-centre case series of 25 patients who underwent ED resuscitative TEE from 2015 to 2019. The objective of this study is to evaluate the feasibility and clinical impact of resuscitative TEE in critically ill patients in the emergency department. Data including changes in working diagnosis, complications, patient disposition, and survival to hospital discharge were also collected.

Results

25 patients (median age 71, 40% female) underwent ED resuscitative TEE. All patients were intubated prior to probe insertion and adequate TEE views were obtained for every patient. The most common indications for resuscitative TEE were cardiac arrest (64%) and undifferentiated shock (28%). Resuscitation management changed in 76% (N = 19) and working diagnosis changed in 76% (N = 19) of patients. Ten patients died in the ED, 15 were admitted to hospital, and eight survived to hospital discharge. There were no immediate complications (0/15) and two delayed complications (2/15), both of which were minor gastrointestinal bleeding.

Conclusions

The use of ED resuscitative TEE is a practical modality that provides useful diagnostic and therapeutic information for critically ill patients in the emergency department, with an excellent rate of adequate cardiac visualization, and a low complication rate.