bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model
Authors: Oda Yukari , Niimi Kaoru , Yoshida Kosuke , Tamauchi Satoshi , Yokoi Akira , Yasui Yuko , Nishiko Yuki , Shibata Mayu , Shimizu Yusuke , Yoshihara Masato , Ikeda Yoshiki , Yoshikawa Nobuhisa , Nishino Kimihiro , Yamamoto Eiko , Kajiyama Hiroaki
Published: November 2023

Background

Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC.

Methods

Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate.

Results

The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour.

Conclusions

We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.
Non-contact meibography changes according to disease activity in rheumatoid arthritis cases
Authors: Mounir Amr , Anbar Mohamed , Awny Islam , Bakheet Tasneem Mohammed , Mounir Ola , Mateen Mossa Elshimaa A
Published: November 2023

Purpose

To measure dry eye disease (DED) activity in rheumatoid arthritis (RA) patients, correlate it with the activity and duration of RA, and objectively measure the degree extent of DED in RA active cases.

Methods

The paper studied the meibomian gland of 30 RA cases referred by the Rheumatology Department, Sohag University Hospitals to Sohag Cornea and Refractive Center, Sohag, Egypt, by infrared non-contact meibography in the Scheimpflug topographer (Sirius, CSO, Italy) from July 2021 to July 2022. The cases fulfilled the RA classification criteria according to the 2010 American College of Rheumatology and European League and underwent full lab investigations. They were distributed to two groups based on the DAS-28 questionnaire. The patients were distributed into low to moderate activity (3.2 < score <  = 5.1) and high activity groups (score > 5.1).

Results

This study included 60 eyes of 30 RA patients. They scored a mean age of (44 ± 10 years), number of swollen joints (3 ± 3), number of tender joints (5 ± 3), duration of disease (8 ± 4), activity of the disease measured by DAS-28 (4.4 ± 0.9), and sex (males were 9.7% vs females 90.3%). The number of swollen joints, tender joints, ESR and DAS-28 were more in the high activity group with the p-value of (0.018, 0.001, < 0.003 and < 0.004), respectively. There are no statistically significant differences between both groups as regards disease duration (p-value of 3.8). The high activity group showed significant affection regarding the mebioscore of the lower and upper lids, total mebioscore, percentage of meibomian glands in upper and lower lids, first non-invasive break-up time test (NIV-BUT) of the tear film, as well as average non-invasive break-up time test (NIavg-BUT). There were moderate correlations between the activity of the disease represented by (DAS-28) and different parameters evaluating eye dryness (meiboscore of the lower and upper lids, total meiboscore, percentage of meibomian glands in upper and lower lids, NIV-BUT of the tear film, and NIavg-BUT of the tear film).

Conclusion

There was no correlation with duration of RA but moderate correlations between the activity of the disease represented by (DAS-28) and different parameters evaluating eye dryness in RA patients with valuable use of noncontact Meibography to evaluate eye dryness in RA cases. Both Meiboscore and Meiboscale of Non-contact Meibography were found to be useful tools in grading of dry eye disease in different activity grades of Rheumatoid Arthritis.
Retinal layers changes in patients with age-related macular degeneration treated with intravitreal anti-VEGF agents
Authors: Zhou Dan , Hu Yan , Qiu Zhongxi , Liu Zirong , Jiang Hongyang , Kawasaki Ryo , Liu Jiang
Published: November 2023

Background

The purpose of this study was to investigate retinal layers changes in patients with age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response.

Methods

This study included 496 patients with AMD or PCV who were treated with anti-VEGF agents and followed up for at least 6 months. A comprehensive analysis of retinal layers affecting visual acuity was conducted. To eliminate the fact that the average thickness calculated may lead to differences tending to converge towards the mean, we proposed that the retinal layer was divided into different regions and the thickness of the retinal layer was analyzed at the same time. The labeled data will be publicly available for further research.

Results

Compared to baseline, significant improvement in visual acuity was observed in patients at the 6-month follow-up. Statistically significant reduction in central retinal thickness and separate retinal layer thickness was also observed (p < 0.05). Among all retinal layers, the thickness of the external limiting membrane to retinal pigment epithelium/Bruch's membrane (ELM to RPE/BrM) showed the greatest reduction. Furthermore, the subregional assessment revealed that the ELM to RPE/BrM decreased greater than that of other layers in each region.

Conclusion

Treatment with anti-VEGF agents effectively reduced retinal thickness in all separate retinal layers as well as the retina as a whole and anti-VEGF treatment may be more targeted at the edema site. These findings could have implications for the development of more precise and targeted therapies for AMD treatment.
Analysis of EEG features and study of automatic classification in first-episode and drug-naïve patients with major depressive disorder
Authors: Huang Yuanyuan , Yi Yun , Chen Qiang , Li Hehua , Feng Shixuan , Zhou Sumiao , Zhang Ziyun , Liu Chenyu , Li Junhao , Lu Qiuling , Zhang Lida , Han Wei , Wu Fengchun , Ning Yuping
Published: November 2023

Background

Major depressive disorder (MDD) has a high incidence and an unknown mechanism. There are no objective and sensitive indicators for clinical diagnosis.

Objective

This study explored specific electrophysiological indicators and their role in the clinical diagnosis of MDD using machine learning.

Methods

Forty first-episode and drug-naïve patients with MDD and forty healthy controls (HCs) were recruited. EEG data were collected from all subjects in the resting state with eyes closed for 10 min. The severity of MDD was assessed by the Hamilton Depression Rating Scale (HAMD-17). Machine learning analysis was used to identify the patients with MDD.

Results

Compared to the HC group, the relative power of the low delta and theta bands was significantly higher in the right occipital region, and the relative power of the alpha band in the entire posterior occipital region was significantly lower in the MDD group. In the MDD group, the alpha band scalp functional connectivity was overall lower, while the scalp functional connectivity in the gamma band was significantly higher than that in the HC group. In the feature set of the relative power of the ROI in each band, the highest accuracy of 88.2% was achieved using the KNN classifier while using PCA feature selection. In the explanatory model using SHAP values, the top-ranking influence feature is the relative power of the alpha band in the left parietal region.

Conclusions

Our findings reveal that the abnormal EEG neural oscillations may reflect an imbalance of excitation, inhibition and hyperactivity in the cerebral cortex in first-episode and drug-naïve patients with MDD. The relative power of the alpha band in the left parietal region is expected to be an objective electrophysiological indicator of MDD.
Understanding and explaining the link between anthroposophy and vaccine hesitancy: a systematic review
Authors: Herzig van Wees Sibylle , Abunnaja Khadija , Mounier-Jack Sandra
Published: November 2023

Background

Due to low vaccination uptake and measles outbreaks across Europe, public health authorities have paid increasing attention to anthroposophic communities. Public media outlets have further described these communities as vaccine refusers or “anti-vaxxers”. The aim of this review was to understand the scope of the problem and explore assumptions about vaccination beliefs in anthroposophic communities. For the purpose of this review, we define anthroposophic communities as people following some/certain views more or less loosely connected to the philosophies of anthroposophy. The systematic review addresses three research questions and (1) collates evidence documenting outbreaks linked to anthroposophic communities, (2) literature on vaccination coverage in anthroposophic communities, and (3) lastly describes literature that summarizes theories and factors influencing vaccine decision-making in anthroposophic communities.

Methods

This is a systematic review using the following databases: Medline, Web of Science, Psycinfo, and CINAHL. Double-blinded article screening was conducted by two researchers. Data was summarized to address the research questions. For the qualitative research question the data was analysed using thematic analysis with the assistance of Nvivo12.0.

Results

There were 12 articles documenting 18 measles outbreaks linked to anthroposophic communities between the years 2000 and 2012. Seven articles describe lower vaccination uptake in anthroposophic communities than in other communities, although one article describes that vaccination coverage in low-income communities with a migrant background was lower than in the anthroposophic community they studied. We found eight articles examining factors and theories influencing vaccine decision making in anthroposophic communities. The qualitative analysis revealed four common themes. Firstly, there was a very broad spectrum of vaccine beliefs among the anthroposophic communities. Secondly, there was a consistent narrative about problems or concerns with vaccines, including toxicity and lack of trust in the system. Thirdly, there was a strong notion of the importance of making individual and well-informed choices as opposed to simply following the masses. Lastly, making vaccine choices different from public health guidelines was highly stigmatized by those outside of the anthroposophic community but also those within the community.

Conclusion

Continuing to further knowledge of vaccine beliefs in anthroposophic communities is particularly important in view of increasing measles rates and potential sudden reliance on vaccines for emerging diseases. However, popular assumptions about vaccine beliefs in anthroposophic communities are challenged by the data presented in this systematic review.
Comparison of different fibula procedures in tibiotalocalcaneal arthrodesis with a retrograde intramedullary nail: a mid-term retrospective study
Authors: He Wenbao , Zhou Haichao , Li Zhendong , Zhao Youguang , Xia Jiang , Li Yongqi , Chen Cheng , Huang Hui , Zhang Yi , Li Bing , Yang Yunfeng
Published: November 2023

Background

Tibiotalocalcaneal (TTC) arthrodesis with a retrograde intramedullary nail for severe tibiotalar and talocalcaneal arthritis has a high fusion rate; however, no studies have focused on how to handle the fibula intraoperatively to achieve better results. This study aimed to compare the efficacies of various fibular procedures.

Methods

We retrospectively reviewed the cases of severe tibiotalar and talocalcaneal arthritis in adults treated with TTC arthrodesis using a retrograde intramedullary nail between January 2012 and July 2017. The patients were divided into three groups according to different fibular procedures: Fibular osteotomy (FO), fibular strut (FS), and fibular preservation (FP). Functional outcomes and pain were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analog scales (VAS), respectively. The operation time, fusion time, radiographic evaluation, and complications were also recorded.

Results

Fifty-eight patients with an average age of 53.2 (range, 32–69) years were enrolled in the final analysis. The numbers of patients enrolled in the three groups were 21, 19, and 18 in the FO, FS, and FP groups, respectively. The mean postoperative follow-up time was 66.0 (range, 60–78) months. All groups showed a high fusion rate (90.5% for FO, 94.7% for FS, and 94.4% for FP) and significant improvement in AOFAS ankle and hindfoot scores and VAS scores at the latest follow-up. There were no significant differences in these parameters among the three groups. The mean operation time of FS (131.3 ± 17.1 min) was longer than that of FO (119.3 ± 11.7 min) and FS (112.2 ± 12.6 min), but the fusion time was shorter (15.1 ± 2.8 weeks for FS, 17.2 ± 1.9 weeks for FO, and 16.8 ± 1.9 weeks for FP). Statistically significant differences were observed in these parameters.

Conclusions

TTC arthrodesis using a retrograde intramedullary nail is an effective procedure with a high rate of fusion to treat severe tibiotalar and talocalcaneal arthritis in adults; however, FSs can shorten fusion time when compared with FO and FP.

Level of clinical evidence

Level 3.
Oral erythroplakia and oral erythroplakia-like oral squamous cell carcinoma – what’s the difference?
Authors: Öhman Jenny , Zlotogorski-Hurvitz Ayelet , Dobriyan Alex , Reiter Shoshana , Vered Marilena , Willberg Jaana , Lajolo Carlo , Siponen Maria
Published: November 2023

Background

Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In particular, lesions that look clinically like erythroplakias, but are histopathologically diagnosed as squamous cell carcinomas are still sometimes called erythroplakias. The purpose of this study is to present demographic and clinicopathologic features of a series of OEs and clinically oral erythroplakia -like squamous cell carcinomas (OELSCC), to study their differences and to discuss the definition of OE.

Methods

A multicenter retrospective case series of OEs and OELSCCs. Descriptive statistics were used to analyze the data.

Results

11 cases of OEs and 9 cases of OELSCCs were identified. The mean age of the OE patients was 71 years and 72.7% were female, while the mean age of the OELSCC patients was 69 years, and all were female. 9% of the OE and 22% of the OELSCC patients had smoked or were current smokers. 72.7% of the OEs and 55.5% of OELSCCs were uniformly red lesions. 63.6% of the OE and 22% of the OELSCC patients had a previous diagnosis of oral lichenoid disease (OLD). The malignant transformation rate of OE was 9% in a mean of 73 months.

Conclusions

OE and OELSCC may arise de novo or in association with OLD. Tobacco and alcohol use were not prevalent in the present cases. The clinical features of OEs and OELSCC are similar, but symptoms, uneven surface and ulceration may be more common in OELSCCs than in OEs. Clinical recognition of OE is important since it may mimic other, more innocuous red lesions of the oral mucosa. The diagnosis of OE requires biopsy and preferably an excision. Clarification of the definition of OE would aid in clinical diagnostics.
Adhesive bond strength of monolithic zirconia ceramic finished with various surface treatments
Authors: Sarıkaya Işıl , Hayran Yeliz
Published: November 2023

Background

This study aimed to investigate different surface treatments thought to increase the bond strength between zirconia ceramic and adhesive resin cement.

Methods

The samples were prepared in 15 × 10 × 2 mm dimensions by cutting off monolithic zirconia ceramic blocks (Incoris TZI; Sirona, Germany). Surface roughness measurements were made with a profilometer, the average surface roughness (Ra1) was recorded, and five different surface treatments were applied. Group 1: Control group. No surface treatment was applied. Group 2: Sandblasted with Al2O3 under pressure of 50 μm. Group 3: Sandblasted with 30 μm Al2O3 - SiOx under pressure, then tribochemical silica coating, silane bonding agent, and ceramic primer were applied. Group 4: Samples were etched in a hot acid solution containing methanol, HCl, and chloride at 100 °C. Group 5: Samples were coated in a solution containing Grade C Aluminum Nitrite at 75 °C for 15 Sects. 12,000 thermal aging was carried out to all samples. Then, samples were bonded to a composite surface (Filtek Z250) with two different types of adhesive cement (Panavia F 2.0, Rely X U200) (n = 10). A load was applied to the samples attached to the Universal Test Device for the SBS, and the SBS was recorded. The surface roughness measurements of all samples were made again, and the average surface roughness Ra2 was recorded. The data was analyzed with a two-way ANOVA test. Bonferroni correction was used for multiple comparisons of the groups. p = 0.005 was accepted as the statistically significant value.

Results

There was no statistically significant difference between the groups in the Ra1 measurements (p = 0.031). There was a statistically significant difference between the Ra2 values of Groups 4 and 5 and the Ra2 values of Groups 1,2 and 3 in the Ra2 measurements (p < 0.001). There was no statistically significant difference between the SBS values of the groups (p > 0.005). Also, there was no statistically significant difference in the SBS values of all groups for the two different cements tested (p > 0.005).

Conclusions

None of the surface treatments applied to monolithic zirconia ceramic samples increased the SBS between ceramic and adhesive resin cement.
Induced abortions among Chinese adolescent girls
Authors: Wang Tian , Si Lei , Jiang Quanbao
Published: November 2023

Background

Induced abortion among adolescent girls is a global public health issue and a serious challenge in China, but still remains under-examined. We aimed to examine the overall trend and characteristics of induced abortions among Chinese adolescent girls and to investigate the factors associated with induced abortion.

Study design

Based on the 2017 China Fertility Survey, this study examined the trend and characteristics of induced abortions among adolescent girls with statistical analysis and multiple indicators of descriptive statistics from period and cohort perspectives, including induced abortion proportion and rate, age-specific cumulative proportion, and age-specific cumulative number of induced abortions in adolescent girls.

Results

Between 1996 and 2016, the proportion and rate of adolescent induced abortions first increased and then decreased, and the mean age at the time of induced abortions among adolescent girls declined. The cumulative proportion of women who had experienced induced abortion at the age of 15–19 in a cohort is less than 2.5% but shows an upward trend. Over 70% of all adolescent induced abortions are premarital. The proportion of women with unintended pregnancy experiences increased and is higher among rural, less educated, and ethnic minority women. Similarly, the prevalence of induced abortion is higher among adolescent girls who live in rural areas, are less educated, and come from ethnic minorities. The cumulative number of induced abortions and premarital abortions increased with later cohorts.

Conclusions

This study shows an upward trend in adolescent-induced abortion and a decline in the age at the time of the induced abortion. Women in later birth cohort have a higher proportion of having experienced adolescent induced abortion. Adolescent girls who live in rural areas, who are less educated, or who are from ethnic minorities, are more likely to undergo induced abortions at the age of 15–19. More appropriate educational efforts and interventions are urgently needed to reduce the incidence of adolescent induced abortions.
Integrated network pharmacology and cellular assay reveal the biological mechanisms of Limonium sinense (Girard) Kuntze against Breast cancer
Authors: Zhao Hualong , Wang Siyuan , Williamson Philip T.F. , Ewing Rob M. , Tang Xinhui , Wang Jialian , Wang Yihua
Published: November 2023

Background

Limonium Sinense (Girard) Kuntze (L. sinense) has been widely used for the treatment of anaemia, bleeding, cancer, and other disorders in Chinese folk medicine. The aim of this study is to predict the therapeutic effects of L. sinense and investigate the potential mechanisms using integrated network pharmacology methods and in vitro cellular experiments.

Methods

The active ingredients of L. sinense were collected from published literature, and the potential targets related to L. sinense were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and DisGeNET enrichment analyses were performed to explore the underlying mechanisms. Molecular docking, cellular experiments, RNA-sequencing (RNA-seq) and Gene Expression Omnibus (GEO) datasets were employed to further evaluate the findings.

Results

A total of 15 active ingredients of L. sinense and their corresponding 389 targets were obtained. KEGG enrichment analysis revealed that the biological effects of L. sinense were primarily associated with “Pathways in cancer”. DisGeNET enrichment analysis highlighted the potential role of L. sinense in the treatment of breast cancer. Apigenin within L. sinense showed promising potential against cancer. Cellular experiments demonstrated that the L. sinense ethanol extract (LSE) exhibited a significant growth inhibitory effect on multiple breast cancer cell lines in both 2D and 3D cultures. RNA-seq analysis revealed a potential impact of LSE on breast cancer. Additionally, analysis of GEO datasets verified the significant enrichment of breast cancer and several cancer-related pathways upon treatment with Apigenin in human breast cancer cells.

Conclusion

This study predicts the biological activities of L. sinense and demonstrates the inhibitory effect of LSE on breast cancer cells, highlighting the potential application of L. sinense in cancer treatment.
A digital educational resource to support and enhance effective mentorship practices of nursing students in nursing homes: a qualitative study
Authors: Frøiland Christina T. , Husebø Anne Marie Lunde , Aase Ingunn , Akerjordet Kristin , Laugaland Kristin
Published: November 2023

Background

There is a grooving body of evidence emphasising the need to support and enhance effective mentorship practices for nursing students in nursing home placements, including strengthening of the pedagogical competence of registered nurse mentors. Owing to the necessity for multifaceted mentoring competence and the challenges of workload registered nurses are facing, the use of flexible digital educational resources has been suggested. However, current knowledge on the effectiveness of digital educational resources in enhancing mentorship practices in nursing homes is scarce. This study aimed to explore the perception of registered nurse mentors regarding the effectiveness of a digital educational resource, particular its usability and value-in-use in supporting and enhancing mentorship practices in nursing homes.

Methods

The study applied an exploratory descriptive qualitative design. Pre- and post-mentoring semi-structured focus group interviews were conducted among a total of 23 registered nurse mentors across three Norwegian nursing homes. The transcribed interviews were thematically analysed. Standards for reporting qualitative research were followed.

Results

The analysis yielded one pre-mentoring theme: (1) predominant enthusiasm and satisfaction and three post-mentoring themes: (2) enhanced confidence and motivation, (3) enhanced mentoring competence in supporting the nursing students’ learning process, and (4) factors influencing the value-in-use of the digital educational resource.

Conclusions

Digital educational resources support effective mentorship practices by enhancing the confidence and motivation in the mentor role and by enabling more goal-oriented supervision and assessment tailored to the learning goals of students. The implementation of digital educational resources to support and enhance effective mentorship practices is an important avenue for further research towards achieving high-quality learning environments in clinical nursing education in general and nursing homes. Based on the study findings, nursing educational institutions should consider offering digital educational resources to develop, support, and advance mentorship training, which may more effectively impact and improve the quality of clinical nursing education.
Occurrence of mosaic trisomy 22 and pericentric inversion of chromosome 9 in a patient with a good prognosis
Authors: Nardelli Aline , Laskoski Larissa Valéria , Luiz Andressa Fernanda , Silveira Maruhen Amir Datsch , d’Arce Luciana Paula Grégio
Published: November 2023

Complete trisomy 22 is a rare chromosomal condition that is incompatible with life. However, mosaic trisomy 22 usually has prolonged survival compatibility and may present a good prognosis depending on the tissues affected. Herein, we described a male patient with the occurrence of mosaic trisomy 22 associated with the inversion of chromosome 9, with karyotype 47, XY, inv (9) (p11q13), + 22 [5] / 46, XY, inv(9) (p11q13) [45] and arr 22q11.1 ~ q13.33(16,417008-51,219,009)x2 ~ 3. It is not possible to infer, in general, the clinical characteristics associated with mosaic trisomy 22. However, the patient presented common clinical features observed in reported cases (in parentheses the percentage observed comparing all reported cases): facial dysmorphia (100%), delay in motor development/growth (82%), cardiac abnormalities (73%), ear abnormalities (55%) and facial and/or body asymmetry (55%), in addition to hypotonia, skin spots, hypoplastic nails. Given the survival and quality of life associated with multidisciplinary treatment, it can be concluded that the patient has a good prognosis. Conclusively, we’re presenting the occurrence of mosaic trisomy 22 and chromosome 9 inversion in the patient with favorable prognosis. Thus, this study proposed a guide which should be inserted in databases of rare genetic conditions to help genetic counselors define mosaic trisomy 22 diagnosis.
Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial
Authors: Afolabi Muhammed O. , Sow Doudou , Agbla Schadrac C. , Fall El Hadji Babacar , Sall Fatimata Bintou , Seck Amadou , Manga Isaac Akhénaton , Mbaye Ibrahima Marietou , Loum Mor Absa , Camara Baba , Niang Diatou , Gueye Babacar , Sene Doudou , Kane Ndéye M’backé , Diop Boubacar , Diouf Awa , Gaye Ndéye Aida , Diouf Marie Pierre , Lo Aminata Colle , Greenwood Brian , Ndiaye Jean Louis A.
Published: November 2023

Background

The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal.

Methods

Female and male children aged 1–14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1–3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1–3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1–3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed.

Results

From 9 to 22 June 2022, 627 children aged 1–14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13–5.00, p = 0.63).

Conclusions

Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model.

Trial registration: The study is registered at Clinical Trial.gov NCT05354258.
Understanding integrated HPV testing and treatment of pre-cancerous cervical cancer in Burkina Faso, Cote d’Ivoire, Guatemala and Philippines: study protocol
Authors: Kabue Mark , Gauvreau Cindy L. , Daceney Nemdia , Bertram Margaret Mary , Shissler Tracey , Reis Veronica , Dodo Mathurin , Garces Ana , Llave Cecilia , Dao Blami , Mohan Diwakar , Huang Lisa
Published: November 2023

Background

Many low- and-middle-income countries are disproportionately burdened by cervical cancer, resulting in high morbidity and mortality. HPV-DNA testing coupled with treatment with thermal ablation is a recommended screening and precancer treatment strategy, but not enough is known about how this can be effectively implemented in the context of integrated services. The (Scale Up Cervical Cancer Elimination by Secondary prevention Strategy, (SUCCESS) project is conducting a study to understand this approach, integrated into existing women’s health services in Burkina Faso, Cote d’Ivoire, Guatemala, and the Philippines (2020–2024).

Methods

A hybrid effectiveness-implementation type III mixed-methods observational study design is used to assess feasibility, acceptability, and costs of integrated service delivery in 10 sites per country, selected considering urban/rural location, facility level, onsite/offsite laboratories, and health services type. In each country, a sample size of 2227 women aged 25–49 years will be enrolled with about 20% being women living with HIV. The primary outcome is proportion of HPV positive women completing precancer treatment, if eligible, within three months of screening. Data collection and analysis includes; facility and client exit surveys, key informant and client interviews, registries and project records extractions, and costing data analysis. Analysis includes descriptive statistics, context description, thematic analysis, and document analysis. Quantitative analyses will be stratified by participant’s HIV status.

Discussion

Recruitment of study participants started in April 2022 (Burkina Faso and Côte d’Ivoire) and August 2022 (Guatemala and the Philippines). Enrolment targets for women screened, client exit, in-depth and key informant interviews conducted were reached in Burkina Faso and Cote d’Ivoire in November 2022. Guatemala and Philippines are expected to complete enrolment by June 2023. Follow-up of study Participants 12-months post-treatment is ongoing and is expected to be completed for all countries by August 2024. In LMICs, integrating cervical cancer secondary prevention services into other health services will likely require specific rather than incidental recruitment of women for screening. Reconfiguration of laboratory infrastructure and planning for sample management must be made well in advance to meet induced demand for screening.

Trail Registration ClinicalTrials.Gov ID: NCT05133661 (24/11/2021).
Modulation of the vitamin D/vitamin D receptor system in osteoporosis pathogenesis: insights and therapeutic approaches
Authors: Li Yanqi , Zhao Pengfei , Jiang Biyun , Liu Kangyong , Zhang Lei , Wang Haotian , Tian Yansheng , Li Kun , Liu Guoqi
Published: November 2023

Osteoporosis is a prevalent bone disorder characterized by low bone mineral density (BMD) and deteriorated bone microarchitecture, leading to an increased risk of fractures. Vitamin D (VD), an essential nutrient for skeletal health, plays a vital role in maintaining bone homeostasis. The biological effects of VD are primarily mediated through the vitamin D receptor (VDR), a nuclear receptor that regulates the transcription of target genes involved in calcium and phosphate metabolism, bone mineralization, and bone remodeling. In this review article, we conduct a thorough literature search of the PubMed and EMBASE databases, spanning from January 2000 to September 2023. Utilizing the keywords “vitamin D,” “vitamin D receptor,” “osteoporosis,” and “therapy,” we aim to provide an exhaustive overview of the role of the VD/VDR system in osteoporosis pathogenesis, highlighting the most recent findings in this field. We explore the molecular mechanisms underlying VDR’s effects on bone cells, including osteoblasts and osteoclasts, and discuss the impact of VDR polymorphisms on BMD and fracture risk. Additionally, we examine the interplay between VDR and other factors, such as hormonal regulation, genetic variants, and epigenetic modifications, that contribute to osteoporosis susceptibility. The therapeutic implications of targeting the VDR pathway for osteoporosis management are also discussed. By bringing together these diverse aspects, this review enhances our understanding of the VD/VDR system’s critical role in the pathogenesis of osteoporosis and highlights its significance as a potential therapeutic target.
Integrative transcriptomic and network pharmacology analysis reveals the neuroprotective role of BYHWD through enhancing autophagy by inhibiting Ctsb in intracerebral hemorrhage mice
Authors: Cai Yiqing , Yu Zhe , Yang Xueping , Luo Weikang , Hu En , Li Teng , Zhu Wenxin , Wang Yang , Tang Tao , Luo Jiekun
Published: November 2023

Background

In this study, we aimed to combine transcriptomic and network pharmacology to explore the crucial mRNAs and specific regulatory molecules of Buyang Huanwu Decoction (BYHWD) in intracerebral hemorrhage (ICH) treatment.

Methods

C57BL/6 mice were randomly divided into three groups: sham, ICH, and BYHWD. BYHWD (43.29 g/kg) was administered once a day for 7 days. An equal volume of double-distilled water was used as a control. Behavioural and histopathological experiments were conducted to confirm the neuroprotective effects of BYHWD. Brain tissues were collected for transcriptomic detection. Bioinformatics analysis were performed to illustrate the target gene functions. Network pharmacology was used to predict potential targets for BYHWD. Next, transcriptomic assays were combined with network pharmacology to identify the potential differentially expressed mRNAs. Immunofluorescence staining, real-time polymerase chain reaction, western blotting, and transmission electron microscopy were performed to elucidate the underlying mechanisms.

Results

BYHWD intervention in ICH reduced neurological deficits. Network pharmacology analysis identified 203 potential therapeutic targets for ICH, whereas transcriptomic assay revealed 109 differentially expressed mRNAs post-ICH. Among these, cathepsin B, ATP binding cassette subfamily B member 1, toll-like receptor 4, chemokine (C–C motif) ligand 12, and baculoviral IAP repeat-containing 5 were identified as potential target mRNAs through the integration of transcriptomics and network pharmacology approaches. Bioinformatics analysis suggested that the beneficial effects of BYHWD in ICH may be associated with apoptosis, animal autophagy signal pathways, and PI3K-Akt and mTOR biological processes. Furthermore, BYHWD intervention decreased Ctsb expression levels and increased autophagy levels in ICH.

Conclusions

Animal experiments in combination with bioinformatics analysis confirmed that BYHWD plays a neuroprotective role in ICH by regulating Ctsb to enhance autophagy.
Pseudo-allergic reactions induced by Chinese medicine injections: a review
Authors: Zou Fanmei , Du Qiuzheng , Zhang Yuanyuan , Zuo Lihua , Sun Zhi
Published: November 2023

Traditional Chinese medicine injections (TCMIs) is a new dosage form of Chinese medicine, which plays a unique role in rescuing patients with critical illnesses that are difficult to replace. With the rapid development and widespread application of TCMIs in recent years, their adverse events have emerged and attracted much attention. Among them, pseudo-allergic reactions, i.e., the most significant adverse reactions occurring with the first dose without immunoglobulin E mediated conditions. Currently, studies on the types of TCMIs and antibiotic mechanisms that cause pseudo-allergic reactions are incomplete, and standard models and technical guidelines for assessing TCMIs have not been established. First, this review describes the causes of pseudo-allergic reactions, in which the components and structures responsible for pseudo-allergic reactions are summarized. Second, the mechanisms by which pseudo-allergic reactions are discussed, including direct stimulation of mast cells and complement activation. Then, research models of pseudo-allergic reaction diseases are reviewed, including animal models and cellular models. Finally, the outlook and future challenges for the development of pseudo-allergic reactions in traditional Chinese medicine (TCM) are outlined. This shed new light on the assessment and risk prevention of pseudo-allergic reactions in TCM and the prevention of clinical adverse reactions in TCM.
Assessing the cardiovascular effects of levothyroxine use in an ageing United Kingdom population (ACEL-UK) protocol: a cohort and target trial emulation study
Authors: Holley Mia , Razvi Salman , Dew Rosie , Maxwell Ian , Wilkes Scott
Published: November 2023

Background

Subclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over.

Methods

This project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage.

Discussion

There needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population.

Trial registration

Not applicable.
Prevalence of plantar ulcer and its risk factors in leprosy: a systematic review and meta‐analysis
Authors: Govindasamy Karthikeyan , Darlong Joydeepa , Watson Samuel I. , Gill Paramjit
Published: November 2023

Background

Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy and its risk factors are scant impeding the development of targeted interventions to prevent and promote healing of ulcers. The aim of this review is to generate evidence on the prevalence of plantar ulcer and its risk factors in leprosy.

Methods

Databases (Medline, Embase, Web of Science, CINAHL, BVS), conference abstracts and reference lists were searched for eligible studies. Studies were included that reported a point prevalence of plantar ulcer and/or its “risk factors” associated with development of ulcers (either causatively or predictively), including individual level, disease related and bio‐mechanical factors. We followed PRISMA guidelines for this review. Random‐effects meta‐analysis was undertaken to estimate the pooled point prevalence of ulcers. Reported risk factors in included studies were narratively synthesised. This review is registered in PROSPERO: CRD42022316726.

Results

Overall, 15 studies (8 for prevalence of ulcer and 7 for risk factors) met the inclusion criteria. The pooled point prevalence of ulcer was 34% (95% CIs: 21%, 46%) and 7% (95% CIs: 4%, 11%) among those with foot anaesthesia and among all people affected by leprosy, respectively. Risk factors for developing ulcers included: unable to feel 10 g of monofilament on sensory testing, pronated/hyper‐pronated foot, foot with peak plantar pressure, foot with severe deformities, and those with lower education and the unemployed.

Conclusions

The prevalence of plantar ulceration in leprosy is as high as 34% among those with loss of sensation in the feet. However, the incidence and recurrence rates of ulceration are least reported. The inability to feel 10 g of monofilament appears to be a strong predictor of those at risk of developing ulcers. However, there is a paucity of evidence on identifying those at risk of developing plantar ulcers in leprosy. Prospective studies are needed to estimate the incidence of ulcers. Identifying individuals at risk of ulcers will help design targeted interventions to minimize risk factors, prevent ulcers and promote ulcer healing.
Differential usage of DNA modifications in neurons, astrocytes, and microglia
Authors: Tooley Kyla B. , Chucair-Elliott Ana J. , Ocañas Sarah R. , Machalinski Adeline H. , Pham Kevin D. , Hoolehan Walker , Kulpa Adam M. , Stanford David R. , Freeman Willard M.
Published: November 2023

Background

Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. In this study, we developed an in vivo tagging mouse model (Camk2a-NuTRAP) for paired isolation of neuronal DNA and RNA without cell sorting and then used this model to assess epigenomic regulation, DNA modifications in particular, of gene expression between neurons and glia.

Results

After validating the cell-specificity of the Camk2a-NuTRAP model, we performed TRAP-RNA-Seq and INTACT-whole genome oxidative bisulfite sequencing (WGoxBS) to assess the neuronal translatome and epigenome in the hippocampus of young mice (4 months old). WGoxBS findings were validated with enzymatic methyl-Seq (EM-Seq) and nanopore sequencing. Comparing neuronal data to microglial and astrocytic data from NuTRAP models, microglia had the highest global mCG levels followed by astrocytes and then neurons, with the opposite pattern observed for hmCG and mCH. Differentially modified regions between cell types were predominantly found within gene bodies and distal intergenic regions, rather than proximal promoters. Across cell types there was a negative correlation between DNA modifications (mCG, mCH, hmCG) and gene expression at proximal promoters. In contrast, a negative correlation of gene body mCG and a positive relationship between distal promoter and gene body hmCG with gene expression was observed. Furthermore, we identified a neuron-specific inverse relationship between mCH and gene expression across promoter and gene body regions.

Conclusions

Neurons, astrocytes, and microglia demonstrate different genome-wide levels of mCG, hmCG, and mCH that are reproducible across analytical methods. However, modification-gene expression relationships are conserved across cell types. Enrichment of differential modifications across cell types in gene bodies and distal regulatory elements, but not proximal promoters, highlights epigenomic patterning in these regions as potentially greater determinants of cell identity. These findings also demonstrate the importance of differentiating between mC and hmC in neuroepigenomic analyses, as up to 30% of what is conventionally interpreted as mCG can be hmCG, which often has a different relationship to gene expression than mCG.