bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin attenuates the production and proliferative effects of prolactin induced by medroxyprogesterone acetate during fertility-sparing treatment for endometrial cancer
Authors: Gu Wenjing , Mitsuhashi Akira , Kobayashi Tatsuya , Shozu Makio
Published: July 2022

Background

Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin.

Methods

In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009–2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting.

Results

MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulatedIGFBP-1andPRLmRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-inducedIGFBP-1andPRLmRNA expression during fertility-sparing treatment and significantly inhibited the upregulation ofIGFBP-1andPRLmRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases.

Conclusions

MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment.
Sustainable palm weevil farming as nutrition supplementation at maternity waiting homes in Liberia
Authors: Reynolds Christopher W. , Horton Madison , Anankware Jacob Paarechuga , Perosky Joseph , Lee HaEun , Nyanplu Aloysius , Zogbaye Barsee , Kofa Alphonso , Lori Jody R.
Published: July 2022

Background

Food insecurity is a global health challenge exacerbated by COVID-19. In Liberia, two-thirds of pregnant women are anemic, one-third of children are stunted, and 70% of households experienced food insecurity due to COVID-19. Edible insects are a nutritious, environmentally responsible, and cost-effective dietary supplement used throughout sub-Saharan Africa. Rearing palm weevil insects at maternity waiting homes (MWHs)—residential dwellings near hospitals where pregnant women await childbirth and receive postpartum services—could serve as a nutritious supplement for expectant mothers in Liberia and provide an income generating activity for MWHs.

Methods

Following a one-day training, sixteen participants established palm weevil rearing sites at four MWHs in Liberia. Pre- and post-knowledge scores were assessed immediately prior to and following training. Pre-and post-knowledge scores were analyzed using paired t-test. Participants tracked two palm weevil rearing cycles (four months), using harvest amounts, turnover, barriers to implementation, and income generated as metrics. The number of women attending MWHs was recorded throughout the study period (July-December 2020).

Results

Sixteen participants from four MWHs completed the training and two rearing cycles (four months) successfully. All participants showed statistically significant increases in knowledge scores following the one-day workshop with a pre-test score of 2.31 and post-test score of 7.75 out of 10 (p < 0.001). Over the 6-month study, 217 women stayed in four MWHs. Larval production from the various rearing centers ranged from 120 to 721 larvae, with all four sites producing enough palm weevil to sustain MWH residents who desired to consume the insects. One site successfully commercialized its harvest to sell approximately 50% for a total of 2,000 LD (13 USD) in income. Three of the four sites continued edible insect production beyond the four-month study period.

Conclusions

An edible insect project using palm weevil larva is one promising intervention as a nutrition supplement for expectant mothers at pre-established MWHs in rural Liberia. Edible insect rearing also has potential as an income generating activity for MWHs. Future studies should focus on addressing common barriers of remote implementation and metric tracking during the COVID-19 pandemic and reinforcing infrastructure to protect larvae rearing supplies.
Occlusal features of 5-year-old Greek children: a cross-sectional national study
Authors: Davidopoulou Sotiria , Arapostathis Konstantinos , Berdouses Elias D. , Kavvadia Katerina , Oulis Constantine
Published: July 2022

Background

Occlusal characteristics of the primary dentition are crucial in predicting and determining permanent tooth alignment and occlusion. The aim of our study was to determine the occlusal characteristics of the primary dentition of 5-year-old children in Greece through a national pathfinder survey.

Methods

A stratified cluster sample of 1222 5-year-old children was selected according to the WHO guidelines for national pathfinder surveys. Five occlusal traits were registered clinically in centric occlusion, separately for the left and right sides: sagittal relationships of the second primary molars and primary canines, overjet, overbite, crossbite, and maxillary and mandibular spacing.

Results

Most children showed a flush terminal plane of primary second molars (44.8%), a class I primary canine relationship (52.2%) and normal overjet (46.4%), but a high prevalence of Class II canine relationship (25.6%) and overjet (37.8%) were also observed. A normal overbite was found in 40% of the children and 40% had a deep overbite. Spacing was apparent in both maxilla (71.1% of children) and mandible (56.4%). The prevalence of open bite and distal step molar relationship significantly rose in children with non-nutritive sucking habits.

Conclusions

Νon-nutritive habits were associated to altered occlusal features. No sex significant differences were found in either the sagittal relationships of second primary molars and primary canines, or overjet, overbite, crossbite and spacing.
Communicating with young children who have a parent dying of a life-limiting illness: a qualitative systematic review of the experiences and impact on healthcare, social and spiritual care professionals
Authors: Wickramasinghe Lasitha M. , Yeo Zhi Zheng , Chong Poh Heng , Johnston Bridget
Published: July 2022

Background

Healthcare professionals play a key role in interacting with children who have a parent with a life-limiting illness. While playing such a role can be challenging, not much is known about how such interactions impact these professionals and affect their ability to render support.

Methods

Four databases were searched with the intention to conduct a qualitative systematic review. Articles were selected based on pre-determined inclusion and exclusion criteria. Their quality was assessed using the tool "Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields”. Findings were analysed using thematic analysis techniques outlined by Thomas and Harden as well as Sandelowski and Barroso. Review was registered with the Review Registry database.

Results

Three themes emerged – healthcare professionals’ discomfort; their assumptions and actions; and potentiating workplace factors. The discomfort had several dimensions: fear of making a situation worse, concern of not being able to cope with emotionally charged situations, and internal conflict that arose when their values clashed with family dynamics.

Conclusion

Healthcare professionals’ sense of discomfort was very pronounced. This discomfort, together with their assumptions, could impact their ability to support children. The organisation played an important role, which was reflected in the work culture, workflow and ability to collaborate with other agencies involved in supporting children. The discomfort was mitigated by having more professional experience, workplace support systems and training on communicating with children. It was apparent that the individual professional did not work alone when supporting children but alongside others within an organisation. As such, issues raised in this review will benefit from multi-faceted solutions.
Barthel Index is a valid and reliable tool to measure the functional independence of cancer patients in palliative care
Authors: dos Santos Barros Vinício , Bassi-Dibai Daniela , Guedes César Leonardo Ribeiro , Morais Daniel Nunes , Coutinho Sabrina Marinho , de Oliveira Simões Gabriel , Mendes Letícia Padilha , da Cunha Leal Plínio , Dibai-Filho Almir Vieira
Published: July 2022

Background

Our objective was to verify the reliability, internal consistency and construct validity of the Barthel Index in Brazilian cancer patients in palliative care.

Methods

We included patients with cancer, both sexes, and age greater than or equal to 18 years. We used to evaluate patients the Barthel Index, Karnofsky Performance Scale (KPS), and European Organization for Research in the Treatment of Cancer Questionnaire-core 15 (EORTC-QLQ-C15-PAL). The measurement properties evaluated in this study were test–retest and inter-rater reliability and construct validity (tested by means of correlations with other instruments).

Results

We included 220 patients for construct validity and a subsample of 27 patients for reliability analyses. We observed adequate reliability (intraclass correlation coefficient ≥ 0.962) and internal consistency (Cronbach’s alpha = 0.942). There were adequate correlations between the Barthel Index and the KPS (rho = 0.766), and the functional capacity domain of the EORTC-QLQ-C15-PAL (rho = -0.698).

Conclusion

The Brazilian version of the Barthel Index presents adequate test–retest and inter-rater reliability, acceptable internal consistency, and valid construct for measuring functional independence in cancer patients.
A cohort study for the development and validation of a reflective inventory to quantify diagnostic reasoning skills in optometry practice
Authors: Edgar Amanda K. , Ainge Lucinda , Backhouse Simon , Armitage James A.
Published: July 2022

Background

Diagnostic reasoning is an essential skill for optometry practice and a vital part of the curriculum for optometry trainees but there is limited understanding of how diagnostic reasoning is performed in optometry or how this skill is best developed. A validated and reliable self-reflective inventory for diagnostic reasoning in optometry, would enable trainees and registered practitioners to benchmark their diagnostic reasoning skills, identify areas of strength and areas for improvement.

Methods

A 41 item self-reflective inventory, the Diagnostic Thinking Inventory, used extensively in the medical field was adapted for use in optometry and called the Diagnostic Thinking Inventory for Optometry (DTI-O). The inventory measures two subdomains of diagnostic reasoning, flexibility in thinking and structured memory. Context based changes were made to the original inventory and assessed for face and content validity by a panel of experts. The inventory was administered to two groups, experienced (qualified) optometrists and second-year optometry students to establish validity and reliability of the self-reflective tool in optometry.

Results

Exploratory Factor Analysis uncovered 13 domain specific items were measuring a single construct, diagnostic reasoning. One misfitting item was removed following Rasch analysis. Two unidimensional subdomains were confirmed in the remaining 12 items: Flexibility in Thinking (χ2 = 12.98, P = 0.37) and Structured Memory (χ2 = 8.74, P = 0.72). The ‘Diagnostic Thinking Inventory for Optometry Short’ (DTI-OS) tool was formed from these items with the total and subdomain scores exhibiting strong internal reliability; Total score Cα = 0.92. External reliability was established by test-retest methodology (ICC 0.92, 95% CI 0.83–0.96, P < .001) and stacked Rasch analysis (one-way ANOVA, F = 0.07, P = 0.80). Qualified optometrists scored significantly higher (P < .001) than students, demonstrating construct validity.

Conclusion

This study showed that the DTI-O and DTI-OS are valid and reliable self-reflective inventories to quantify diagnostic reasoning ability in optometry. With no other validated tool to measure this metacognitive skill underpinning diagnostic reasoning a self-reflective inventory could support the development of diagnostic reasoning in practitioners and guide curriculum design in optometry education.
The perception of health care quality by primary health care managers in Ukraine
Authors: Anufriyeva Valentyna , Pavlova Milena , Stepurko Tetiana , Groot Wim
Published: July 2022

Background

Ukraine is reforming its health care system to improve quality of health care. Insight into how primary health care managers perceive quality is important for the ongoing reform as well as for the improvement of medical services.

Methods

An online survey was conducted as part of the Ukrainian-Swiss project “Medical Educational Development” in April–May 2019 based on the contact list of USAID project “Health Reform Support”, and additionally on the database of the National Health Service of Ukraine and other channels. Data were analyzed using descriptive statistics and qualitative data analysis.

Results

In total, 302 health care managers took part in the study. The majority of primary health care managers perceive quality in health care as process quality. They associate quality mostly with compliance to standards. At the same time, primary health care managers prefer to assess outcome quality via a system of indicators and feedback. There appears to be a lack of consensus about health care quality. This may be due to a lack of awareness of the national strategy for better quality of health care service.

Conclusions

Our study provides new insights into primary care managers' perceptions of health care quality in Ukraine. The absence of a clear consensus about quality complicates the discussion about quality and how to measure quality in health care. This appears to be one of the obstacles to system-wide quality improvement.
Reliability and validity of the Psychiatric Inpatient Patient Experience Questionnaire – Continuous Electronic Measurement (PIPEQ-CEM)
Authors: Iversen Hilde Hestad , Haugum Mona , Bjertnaes Oyvind
Published: July 2022

Background

The increasing emphasis on patient-centred care has accelerated the demand for high-quality assessment instruments, but the development and application of measures of the quality of care provided for mental health have lagged behind other areas of medicine. The main objective of this study was to determine the psychometric properties of the Psychiatric Inpatient Patient Experience Questionnaire – Continuous Electronic Measurement (PIPEQ-CEM), which consists of large-scale measurements from a Norwegian population. The change from cross-sectional surveys to continuous measurements necessitated further validation of the instrument. The secondary objective was to develop a short version of the PIPEQ-CEM.

Methods

The data included responses from the first year of continuous measurement, and included adult inpatients (age ≥ 18 years) who received specialized mental healthcare from 191 different sections in Norway (n = 3,249). Missing data, ceiling effects, factor structure and internal consistency levels were assessed. The short scale was developed by exploring missing items, ceiling effects, results from exploratory factor analysis (EFA) and item performance from item response theory (IRT) analyses.

Results

Psychometric testing supported previous results and illustrated that the PIPEQ-CEM comprises three empirically based scales with good internal consistency, reliability and validity, and covers structure and facilities, patient-centred interactions, and outcomes. A seven-item short form was developed, which provides an efficient approach for brief yet comprehensive measurements that can be applied in the future.

Conclusion

The PIPEQ-CEM can be recommended for use in future national surveys that assess patient experience with inpatient psychiatric care in Norway and in other countries with similar healthcare systems. The short form can be applied where respondent burden and cognitive load are crucial issues.
Identification of a broad-spectrum lytic Myoviridae bacteriophage using multidrug resistant Salmonella isolates from pig slaughterhouses as the indicator and its application in combating Salmonella infections
Authors: Zhao Mengfei , Xie Rui , Wang Shuang , Huang Xi , Yang Hao , Wu Wenqing , Lin Lin , Chen Hongjian , Fan Jie , Hua Lin , Liang Wan , Zhang Jianmin , Wang Xiangru , Chen Huanchun , Peng Zhong , Wu Bin
Published: July 2022

Background

Salmonella is a leading foodborne and zoonotic pathogen, and is widely distributed in different nodes of the pork supply chain. In recent years, the increasing prevalence of antimicrobial resistant Salmonella poses a threat to global public health. The purpose of this study is to the prevalence of antimicrobial resistant Salmonella in pig slaughterhouses in Hubei Province in China, and explore the effect of using lytic bacteriophages fighting against antimicrobial resistant Salmonella.

Results

We collected a total of 1289 samples including anal swabs of pigs (862/1289), environmental swabs (204/1289), carcass surface swabs (36/1289) and environmental agar plates (187/1289) from eleven slaughterhouses in seven cities in Hubei Province and recovered 106 Salmonella isolates. Antimicrobial susceptibility testing revealed that these isolates showed a high rate of antimicrobial resistance; over 99.06% (105/106) of them were multidrug resistant. To combat these drug resistant Salmonella, we isolated 37 lytic phages using 106 isolates as indicator bacteria. One of them, designated ph 2–2, which belonged to the Myoviridae family, displayed good capacity to kill Salmonella under different adverse conditions (exposure to different temperatures, pHs, UV, and/or 75% ethanol) and had a wide lytic spectrum. Evaluation in mouse models showed that ph 2–2 was safe and saved 80% (administrated by gavage) and 100% (administrated through intraperitoneal injection) mice from infections caused by Salmonella Typhimurium.

Conclusions

The data presented herein demonstrated that Salmonella contamination remains a problem in some pig slaughter houses in China and Salmonella isolates recovered in slaughter houses displayed a high rate of antimicrobial resistance. In addition, broad-spectrum lytic bacteriophages may represent a good candidate for the development of anti-antimicrobial resistant Salmonella agents.
Does the socioeconomic status predict health service utilization in persons with enhanced health care needs? Results from a population-based survey in persons with spinal cord lesions from Switzerland
Authors: Fekete Christine , Debnar Caroline , Scheel-Sailer Anke , Gemperli Armin
Published: July 2022

Background

Evidence suggests that the socioeconomic status (SES) affects individuals’ health service utilization. Spinal cord injury is a condition that often leads to physical impairments and enhanced health care needs. It therefore presents an informative and yet under-researched case in point to investigate social inequalities in health service utilization. This study aims to describe associations between SES and health service utilization in adults with spinal cord injury from Switzerland.

Methods

We use cross-sectional data from 1,294 participants of the Swiss Spinal Cord Injury Cohort Study community survey 2017. SES was operationalized with education, household income, perceived financial hardship, subjective status, and granting of supplementary financial benefits. Health service utilization was assessed with information on visits to 13 different health care providers and four health care institutions (inpatient stays, outpatient clinics, emergency departments, specialized spinal cord centers) during the past 12 months. The dichotomized outcomes on service utilization (visited vs. not visited) were regressed on SES indicators, including adjustments for sociodemographics, lesion characteristics, and health status.

Results

Persons with higher SES reported higher likelihood for specialist, dentist, and dental hygienist visits and reported utilizing a larger number of different care providers. Further, specific SES indicators were associated with certain care provider visits (i.e., higher education and subjective status: higher odds for pharmacist visits; higher income: higher odds for natural healer visits; higher subjective status: higher odds for chiropractor visits; supplementary benefit granting: higher odds for general practitioner and home care service visits). We found statistically non-significant trends towards lower likelihood for inpatient stays, outpatient clinic and emergency department visits and enhanced likelihood for specialized spinal cord-center visits in higher SES groups.

Conclusions

This study generally supports the claim that basic health care provision is guaranteed for all patients with spinal cord injury in Switzerland, independently of their SES. However, social inequalities were still observed for the utilization of specific providers, such as oral health care providers. Given that oral health is key for health maintenance in persons with spinal cord injury, specific interventions to enhance regular dental check-ups in lower SES groups are highly recommended.
Retraction Note to: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation
Authors: Han Mingli , Gu Yuanting , Lu Pengwei , Li Jingyi , Cao Hui , Li Xiangke , Qian Xueke , Yu Chao , Yang Yunqing , Yang Xue , Han Na , Dou Dongwei , Hu Jianguo , Dong Huaying
Published: July 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-020-1145-5.
Psychometric properties of the 12-item WHODAS applied through phone survey: an experience in PERSIAN Traffic Cohort
Authors: Shahedifar Nasrin , Sadeghi-Bazargani Homayoun , Asghari-Jafarabadi Mohammad , Farahbakhsh Mostafa , Bazargan-Hejazi Shahrzad
Published: July 2022

Background

Due to limited capability to function in post-injury daily life injury, survivors need to be reliably assessed without need to commute more than necessary. The key action is to determine the level of functioning difficulties. Having the opportunity of conducting a national post-crash traffic safety and health cohort study, we aimed to translate into Persian and assess the psychometric properties of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) through phone surveys six month post injury.

Methods

First, having World Health Organization permission, we tested the translation validity by forward translation, expert panel evaluation, back-translation, pre-testing and cognitive interviewing, and finalizing the Persian WHODAS. Then, through a psychometric study within a national cohort platform, the validity, reliability and applicability of the 12-item WHODAS was assessed through phone surveys. We included data of 255 road traffic injury patients enrolled from the cohort at six-month follow-up. The psychometric assessment (internal consistency reliability and stability reliability) was conducted on test–retest data of 50 patients with an average 7-day time span. An exploratory factor analysis tested the construct validity using extraction method of principal component factor and oblique rotation on data from 255 patients. Regarding the multiple criteria including an eigenvalue > 0.9, Cattell’s scree test, cumulative variance, and the theoretical basis, the minimum number of factors were retained. Data were analyzed using STATA statistical software package.

Results

The respondents were mostly male (81%), employed (71%), educated (87%), and with a mean age of 37.7(14.9). The Persian version had high internal consistency reliability (Cronbach’s α = 0.93) and excellent stability reliability (ICC = 0.97, 95% CI: 0.92–0.98). An exploratory factor analysis retained four factors defining 86% of all the variance. Factors of Self-care, Mobility, and Cognition were completely retained.

Conclusions

The brief Pesrian WHODAS 2.0 was highly reliable and valid to be applied through phone interviews post injury.
The efficient circulating immunoscore predicts prognosis of patients with advanced gastrointestinal cancer
Authors: Zhao Yamei , Tang Yan , Qin Hanlin , Feng Kehai , Hu Changlu
Published: July 2022

Background

Immunoscore from tumor tissues was initially established to evaluate the prognosis of solid tumor patients. However, the feasibility of circulating immune score (cIS) for the prognosis of advanced gastrointestinal cancers (AGC) has not been reported.

Material and methods

Peripheral venous blood was collected from 64 untreated AGC patients. We utilized flow cytometry to determine several immune cell subpopulations, including CD8+ and CD4+ T cells, NK cells, and CD4 + CD25 + CD127low Tregs. The circulating immune score 1 (cIS1) was assessed according to the proportions of CD4+, CD8+ T cells, and NK cell, whereas circulating immune score 2 (cIS2) was derived from the proportions of CD4+, CD8+ T cell, and CD4 + CD25 + CD127low Tregs. The prognostic role of cIS for progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan–Meier curves and Cox multivariate models. Receiver operating characteristic (ROC) curves were depicted to compare the prognostic values of cIS1 and cIS2.

Results

AGC patients with high cIS1(≥ 2) and cIS2(≥ 2) had significantly longer PFS (cIS1: median PFS, 11 vs. 6.7 months, P = 0.001; cIS2: 12 vs. 5.8 months, P < 0.0001) and OS (cIS1: median OS, 12 vs. 7.9 months, P = 0.0004; cIS2: 12.8 vs. 7.4 months, P < 0.0001) than those with low cIS1 and low cIS2. The areas under ROC curves (AUROCs) of cIS1 and cIS2 for OS were 0.526 (95% confidence interval; 95% CI 0.326–0.726) and 0.603 (95% CI 0.427–0.779, P = 0.332), whereas AUROC of cIS2 for PFS was larger than that of cIS1 0.735 (95% CI 0.609–0.837) vs 0.625 (95% CI 0.495–0.743) (P = 0.04)).

Conclusion

The cIS can be applied to predict the prognosis of untreated AGC patients. Compared with cIS1, cIS2 displayed superior prognostic value for PFS prediction.
Modulation of C5a–C5aR1 signaling alters the dynamics of AD progression
Authors: Carvalho Klebea , Schartz Nicole D. , Balderrama-Gutierrez Gabriela , Liang Heidi Y. , Chu Shu-Hui , Selvan Purnika , Gomez-Arboledas Angela , Petrisko Tiffany J. , Fonseca Maria I. , Mortazavi Ali , Tenner Andrea J.
Published: July 2022

Background

The complement system is part of the innate immune system that clears pathogens and cellular debris. In the healthy brain, complement influences neurodevelopment and neurogenesis, synaptic pruning, clearance of neuronal blebs, recruitment of phagocytes, and protects from pathogens. However, excessive downstream complement activation that leads to generation of C5a, and C5a engagement with its receptor C5aR1, instigates a feed-forward loop of inflammation, injury, and neuronal death, making C5aR1 a potential therapeutic target for neuroinflammatory disorders. C5aR1 ablation in the Arctic (Arc) model of Alzheimer’s disease protects against cognitive decline and neuronal injury without altering amyloid plaque accumulation.

Methods

To elucidate the effects of C5a–C5aR1 signaling on AD pathology, we crossed Arc mice with a C5a-overexpressing mouse (ArcC5a+) and tested hippocampal memory. RNA-seq was performed on hippocampus and cortex from Arc, ArcC5aR1KO, and ArcC5a+ mice at 2.7–10 months and age-matched controls to assess mechanisms involved in each system. Immunohistochemistry was used to probe for protein markers of microglia and astrocytes activation states.

Results

ArcC5a+ mice had accelerated cognitive decline compared to Arc. Deletion of C5ar1 delayed or prevented the expression of some, but not all, AD-associated genes in the hippocampus and a subset of pan-reactive and A1 reactive astrocyte genes, indicating a separation between genes induced by amyloid plaques alone and those influenced by C5a–C5aR1 signaling. Biological processes associated with AD and AD mouse models, including inflammatory signaling, microglial cell activation, and astrocyte migration, were delayed in the ArcC5aR1KO hippocampus. Interestingly, C5a overexpression also delayed the increase of some AD-, complement-, and astrocyte-associated genes, suggesting the possible involvement of neuroprotective C5aR2. However, these pathways were enhanced in older ArcC5a+ mice compared to Arc. Immunohistochemistry confirmed that C5a–C5aR1 modulation in Arc mice delayed the increase in CD11c-positive microglia, while not affecting other pan-reactive microglial or astrocyte markers.

Conclusion

C5a–C5aR1 signaling in AD largely exerts its effects by enhancing microglial activation pathways that accelerate disease progression. While C5a may have neuroprotective effects via C5aR2, engagement of C5a with C5aR1 is detrimental in AD models. These data support specific pharmacological inhibition of C5aR1 as a potential therapeutic strategy to treat AD.
Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone
Authors: Norton Emily S. , Whaley Lauren A. , Ulloa-Navas María José , García-Tárraga Patricia , Meneses Kayleah M. , Lara-Velazquez Montserrat , Zarco Natanael , Carrano Anna , Quiñones-Hinojosa Alfredo , García-Verdugo José Manuel , Guerrero-Cázares Hugo
Published: July 2022

Background

Glioblastoma (GBM) is the most aggressive and common type of primary brain tumor in adults. Tumor location plays a role in patient prognosis, with tumors proximal to the lateral ventricles (LVs) presenting with worse overall survival, increased expression of stem cell genes, and increased incidence of distal tumor recurrence. This may be due in part to interaction of GBM with factors of the subventricular zone (SVZ), including those contained within the cerebrospinal fluid (CSF). However, direct interaction of GBM tumors with CSF has not been proved and would be hindered in the presence of an intact ependymal cell layer.

Methods

Here, we investigate the ependymal cell barrier and its derived extracellular matrix (ECM) fractones in the vicinity of a GBM tumor. Patient-derived GBM cells were orthotopically implanted into immunosuppressed athymic mice in locations distal and proximal to the LV. A PBS vehicle injection in the proximal location was included as a control. At four weeks post-xenograft, brain tissue was examined for alterations in ependymal cell health via immunohistochemistry, scanning electron microscopy, and transmission electron microscopy.

Results

We identified local invading GBM cells within the LV wall and increased influx of CSF into the LV-proximal GBM tumor bulk compared to controls. In addition to the physical disruption of the ependymal cell barrier, we also identified increased signs of compromised ependymal cell health in LV-proximal tumor-bearing mice. These signs include increased accumulation of lipid droplets, decreased cilia length and number, and decreased expression of cell channel proteins. We additionally identified elevated numbers of small fractones in the SVZ within this group, suggesting increased indirect CSF-contained molecule signaling to tumor cells.

Conclusions

Our data is the first to show that LV-proximal GBMs physically disrupt the ependymal cell barrier in animal models, resulting in disruptions in ependymal cell biology and increased CSF interaction with the tumor bulk. These findings point to ependymal cell health and CSF-contained molecules as potential axes for therapeutic targeting in the treatment of GBM.
Binning long reads in metagenomics datasets using composition and coverage information
Authors: Wickramarachchi Anuradha , Lin Yu
Published: July 2022

Background

Advancements in metagenomics sequencing allow the study of microbial communities directly from their environments. Metagenomics binning is a key step in the species characterisation of microbial communities. Next-generation sequencing reads are usually assembled into contigs for metagenomics binning mainly due to the limited information within short reads. Third-generation sequencing provides much longer reads that have lengths similar to the contigs assembled from short reads. However, existing contig-binning tools cannot be directly applied on long reads due to the absence of coverage information and the presence of high error rates. The few existing long-read binning tools either use only composition or use composition and coverage information separately. This may ignore bins that correspond to low-abundance species or erroneously split bins that correspond to species with non-uniform coverages. Here we present a reference-free binning approach, LRBinner, that combines composition and coverage information of complete long-read datasets. LRBinner also uses a distance-histogram-based clustering algorithm to extract clusters with varying sizes.

Results

The experimental results on both simulated and real datasets show that LRBinner achieves the best binning accuracy in most cases while handling the complete datasets without any sampling. Moreover, we show that binning reads using LRBinner prior to assembly reduces computational resources required for assembly while attaining satisfactory assembly qualities.

Conclusion

LRBinner shows that deep-learning techniques can be used for effective feature aggregation to support the metagenomics binning of long reads. Furthermore, accurate binning of long reads supports improvements in metagenomics assembly, especially in complex datasets. Binning also helps to reduce the resources required for assembly. Source code for LRBinner is freely available at https://github.com/anuradhawick/LRBinner.
DUB1 suppresses Hippo signaling by modulating TAZ protein expression in gastric cancer
Authors: Wang Dehai , Li Zhongbo , Li Xin , Yan Cheng , Yang Huijie , Zhuang Ting , Wang Xiao , Zang Yifeng , Liu Ziping , Wang Tianshi , Jiang Rixia , Su Peng , Zhu Jian , Ding Yinlu
Published: July 2022

Background

The Hippo pathway functions as a tumor suppressor pathway in human cancers, while dysfunction of the Hippo pathway is frequently observed in malignancies. Although YAP/TAZ activity is tightly controlled by the phosphorylation cascade of the MST-LATS-YAP/TAZ axis, it is still unclear why the YAP/TAZ proteins are activated in human cancers despite Hippo pathway activation. Recent studies have suggested that in addition to phosphorylation, several other posttranslational modifications, including ubiquitination, also play critical roles in modulating TAZ function.

Methods

We used several gastric cancer cell lines and performed western blot analysis, real-time PCR, immunoprecipitation assays, and in vitro ubiquitination assays and established a xenograft mouse model.

Results

Here, by screening a DUB (deubiquitinase) siRNA library, we discovered that DUB1 functions as a critical modulator that facilitates gastric cancer stemness and progression by deubiquitinating and activating the TAZ protein. We also found that DUB1 expression was elevated in gastric cancer and that elevated DUB1 expression correlated with TAZ activation and poor survival. DUB1 associates with the TAZ protein and deubiquitinates TAZ at several lysine residues, which subsequently stabilizes TAZ and facilitates its function.

Conclusions

Our study revealed a novel deubiquitinase in the Hippo/TAZ axis and identified one possible therapeutic target for Hippo-driven gastric cancer.
Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance
Authors: Wang Xiaolin , Zhang Jiahui , Cao Guozhen , Hua Jinghan , Shan Ge , Lin Wenchu
Published: July 2022

Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis, primarily caused by metastatic lesions. Improved understanding of GC metastasis at the molecular level yields meaningful insights into potential biomarkers and therapeutic targets. Covalently closed circular RNAs (circRNAs) have emerged as crucial regulators in diverse human cancers including GC. Furthermore, accumulating evidence has demonstrated that circRNAs exhibit the dysregulated patterns in GC and have emerged as crucial regulators in GC invasion and metastasis. However, systematic knowledge regarding the involvement of circRNAs in metastatic GC remains obscure. In this review, we outline the functional circRNAs related to GC metastasis and drug resistance and discuss their underlying mechanisms, providing a comprehensive delineation of circRNA functions on metastatic GC and shedding new light on future therapeutic interventions for GC metastases.
New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches
Authors: Zarenezhad Elham , Montazer Mohammad Nazari , Tabatabaee Masoumeh , Irajie Cambyz , Iraji Aida
Published: July 2022

The simple and greener one-pot approach for the synthesis of biscoumarin derivatives using catalytic amounts of nano-MoO3catalyst under mortar-pestle grinding was described. The use of non-toxic and mild catalyst, cost-effectiveness, ordinary grinding, and good to the excellent yield of the final product makes this procedure a more attractive pathway for the synthesis of biologically remarkable pharmacophores. Accordingly, biscoumarin derivatives were successfully extended in the developed protocols.Next, a computational investigation was performed to identify the potential biological targets of this set of compounds. In this case, first, a similarity search on different virtual libraries was performed to find an ideal biological target for these derivatives. Results showed that the synthesized derivatives can be α-glucosidase inhibitors. In another step, molecular docking studies were carried out against human lysosomal acid-alpha-glucosidase (PDB ID: 5NN8) to determine the detailed binding modes and critical interactions with the proposed target. In silico assessments showed the gold score value in the range of 17.56 to 29.49. Additionally, molecular dynamic simulations and the MM-GBSA method of the most active derivative against α-glucosidase were conducted to study the behavior of selected compounds in the biological system. Ligand 1 stabilized after around 30 ns and participated in various interactions with Trp481, Asp518, Asp616, His674, Phe649, and Leu677 residues.
The IMD and Toll canonical immune pathways of Triatoma pallidipennis are preferentially activated by Gram-negative and Gram-positive bacteria, respectively, but cross-activation also occurs
Authors: Alejandro Alvarado-Delgado , Lilia Juárez-Palma , Jesús Maritinez-Bartneche , Henry Rodriguez Mario
Published: July 2022

Background

Antimicrobial peptides (AMPs) participate in the humoral immune response of insects eliminating invasive microorganisms. The immune deficiency pathway (IMD) and Toll are the main pathways by which the synthesis of these molecules is regulated in response to Gram-negative (IMD pathway) or Gram-positive (Toll pathway) bacteria. Various pattern-recognition receptors (PRRs) participate in the recognition of microorganisms, such as pgrp-lc and toll, which trigger signaling cascades and activate NF-κB family transcription factors, such as relish, that translocate to the cell nucleus, mainly in the fat body, inducing AMP gene transcription.

Methods

T. pallidipennis inhibited in Tppgrp-lc, Tptoll, and Tprelish were challenged with E. coli and M. luteus to analyze the expression of AMPs transcripts in the fat body and to execute survival assays.

Results

In this work we investigated the participation of the pgrp-lc and toll receptor genes and the relish transcription factor (designated as Tppgrp-lc, Tptoll, and Tprelish), in the transcriptional regulation of defensin B, prolixicin, and lysozyme B in Triatoma pallidipennis, one of the main vectors of Chagas disease. AMP transcript abundance was higher in the fat body of blood-fed than non-fed bugs. Challenge with Escherichia coli or Micrococcus luteus induced differential increases in AMP transcripts. Additionally, silencing of Tppgrp-lc, Tptoll, and Tprelish resulted in reduced AMP transcription and survival of bugs after a bacterial challenge.

Conclusions

Our findings demonstrated that the IMD and Toll pathways in T. pallidipennis preferentially respond to Gram-negative and Gram-positive bacteria, respectively, by increasing the expression of AMP transcripts, but cross-induction also occurs.

Graphical Abstract
Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report
Authors: Ruver-Martins Ana Carolina , Bicca Maíra Assunção , de Araujo Fabiano Soares , de Noronha Sales Maia Beatriz Helena Lameiro , Pamplona Fabrício Alano , da Silva Elton Gomes , Nascimento Francisney Pinto
Published: July 2022

Background

Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer’s disease, and cannabinoid-based therapy appears to be a feasible possibility.

Case presentation

This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer’s disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-Cognitive Subscale were performed.

Conclusions

Here we provide original evidence that cannabinoid microdosing could be effective as an Alzheimer’s disease treatment while preventing major side effects. This is an important step toward dissociating cannabinoids’ health-improving effects from potential narcotic-related limitations.
Transjugular intrahepatic portosystemic shunt, local thrombaspiration, and lysis for management of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vector-vaccine-induced thrombotic thrombocytopenia: a case report
Authors: Stoll Sandra Emily , Werner Patrick , Wetsch Wolfgang A. , Dusse Fabian , Bunck Alexander C. , Kochanek Matthias , Popp Felix , Schmidt Thomas , Bruns Christiane , Böttiger Bernd W.
Published: July 2022

Introduction

Recombinant adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2 have been observed to be associated with vaccine-induced immune thrombotic thrombocytopenia. Though vaccine-induced immune thrombotic thrombocytopenia is a rare complication after vaccination with recombinant adenoviral vector vaccines, it can lead to severe complications. In vaccine-induced immune thrombotic thrombocytopenia, the vector vaccine induces heparin-independent production of platelet factor 4 autoantibodies, resulting in platelet activation and aggregation. Therefore, patients suffering from vaccine-induced immune thrombotic thrombocytopenia particularly present with signs of arterial or venous thrombosis, often at atypical sites, but also signs of bleeding due to disseminated intravascular coagulation and severe thrombocytopenia. We describe herein a rare case of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia.

Case summary (main symptoms and therapeutic interventions)

This case report presents the diagnosis and treatment of a healthy 29-year-old male Caucasian patient suffering from an extended portomesenteric thrombosis associated with atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia after the first dose of an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 [ChAdOx1 nCoV-19 (AZD1222)]. Therapeutic management of vaccine-induced immune thrombotic thrombocytopenia initially focused on systemic anticoagulation avoiding heparin and the application of steroids and intravenous immune globulins as per the recommendations of international societies of hematology and hemostaseology. Owing to the atraumatic splenic rupture and extended portomesenteric thrombosis, successful management of this case required splenectomy with additional placement of a transjugular intrahepatic portosystemic shunt to perform local thrombaspiration, plus repeated local lysis to reconstitute hepatopetal blood flow.

Conclusion

The complexity and wide spectrum of the clinical picture in patients suffering from vaccine-induced immune thrombotic thrombocytopenia demand an early interdisciplinary diagnostic and therapeutic approach. Severe cases of portomesenteric thrombosis in vaccine-induced immune thrombotic thrombocytopenia, refractory to conservative management, may require additional placement of a transjugular intrahepatic portosystemic shunt, thrombaspiration, thrombolysis, and surgical intervention for effective management.
Pooled coverage of community based health insurance scheme enrolment in Ethiopia, systematic review and meta-analysis, 2016–2020
Authors: Tahir Ahmed , Abdilahi Abdulahi Omer , Farah Abdifatah Elmi
Published: July 2022

Background

Community Based Health Insurance (CBHI) is a type of health insurance program that provides financial protection against the cost of illness and improving access to health care services for communities engaged in the informal sector. In Ethiopia, the coverage of CBHI enrolment varies across regions and decision of household enrolment is affected by different factors. There are pocket studies on CBHI scheme with different coverage in Ethiopia and there is no pooled study on CBHI enrolment coverage in Ethiopia for better understanding the scheme and decision making. The aim of this systematic review and meta-analysis was to identify the pooled coverage of CBHI enrolment in Ethiopia to understand its policy implications.

Methods

The systematic review and meta-analysis was done by adhering the PRISMA guideline with exhaustive search in PubMed/Medline, HINARI, SCOPUS and Google scholar complemented by manual search. Two authors independently selected studies, extracted data, and assessed quality of studies. The I2 test statistic was used to test heterogeneity among studies. The overall coverage of CBHI scheme was estimated by using random-effects model.

Result

Among 269 identified, 17 studies were included in this meta-analysis and the overall coverage of CBHI scheme was 45% (95% CI 35%, 55%) in Ethiopia. The sub-group analysis shows higher enrolment rate 55.97 (95%CI: 41.68, 69.77) in earlier (2016–2017) studies than recent 37.33 (95%CI: 24.82, 50.77) studies (2018–2020).

Conclusion

The pooled coverage of CBHI enrolment is low in Ethiopia compared the national target of 80% set for 2020. It is also concentrated in only major regions of the country. The finding of the study helps national decision making for CBHI scheme service improvement. Due attention to be given to improving geographic expansion of CBHI and to the declining coverages with in the CBHI implementing regions by addressing the main bottlenecks restraining coverages.

Trial registration

The protocol of this systematic review and meta-analysis was published in PROSPERO with registration number: CRD42021252762.