bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactive glass for periodontal regeneration: a systematic review
Authors: Motta Chiara , Cavagnetto Davide , Amoroso Federico , Baldi Ileana , Mussano Federico
Published: May 2023

Background

One of the major clinical challenges of this age could be represented by the possibility to obtain a complete regeneration of infrabony defects. Over the past few years, numerous materials and different approaches have been developed to obtain bone and periodontal healing. Among all biomaterials, bioglasses (BG) are one of the most interesting due to their ability to form a highly reactive carbonate hydroxyapatite layer. Our aim was to systematically review the literature on the use and capability of BG for the treatment of periodontal defects and to perform a meta-analysis of their efficacy.

Methods

A search of MEDLINE/PubMed, Cochrane Library, Embase and DOSS was conducted in March 2021 to identify randomized controlled trials (RCTs) using BG in the treatment of intrabony and furcation defects. Two reviewers selected the articles included in the study considering the inclusion criteria. The outcomes of interest were periodontal and bone regeneration in terms of decrease of probing depth (PD) and gain of clinical attachment level (CAL). A network meta-analysis (NMA) was fitted, according to the graph theory methodology, using a random effect model.

Results

Through the digital search, 46 citations were identified. After duplicate removal and screening process, 20 articles were included. All RCTs were retrieved and rated following the Risk of bias 2 scale, revealing several potential sources of bias. The meta-analysis focused on the evaluation at 6 months, with 12 eligible articles for PD and 10 for CAL. As regards the PD at 6 months, AUTOGENOUS CORTICAL BONE, BIOGLASS and PLATELET RICH FIBRIN were more efficacious than open flap debridement alone, with a statistically significant standardized mean difference (SMD) equal to -1.57, -1.06 and − 2.89, respectively. As to CAL at 6 months, the effect of BIOGLASS is reduced and no longer significant (SMD = -0.19, p-value = 0.4) and curiously PLATELET RICH FIBRIN was more efficacious than OFD (SMD =-4.13, p-value < 0.001) in CAL gain, but in indirect evidence.

Conclusions

The present review partially supports the clinical efficacy of BG in periodontal regeneration treatments for periodontal purposes. Indeed, the SMD of 0.5 to 1 in PD and CAL obtained with BG compared to OFD alone seem clinically insignificant even if it is statistically significant. Heterogeneity sources related to periodontal surgery are multiple, difficult to assess and likely hamper a quantitative assessment of BG efficacy.
Using document phenomenology to investigate academic failure among year 1 undergraduate Malaysian medical students
Authors: Khairul Anhar Holder Nurul Atira , Pallath Vinod , Vadivelu Jamuna , Foong Chan Choong
Published: May 2023

Background

Academic failure is common among medical schools worldwide. However, the process behind this failure itself is underexplored. A deeper understanding of this phenomenon may avert the vicious cycle of academic failure. Hence, this study investigated the process of academic failure among medical students in Year 1.

Methods

This study employed a document phenomenological approach, which is a systematic process to examine documents, interpret them to attain understanding, and develop empirical knowledge of the phenomenon studied. Using document analysis, interview transcripts and reflective essays of 16 Year 1 medical students who experienced academic failure were analysed. Based on this analysis, codes were developed and further reduced into categories and themes. Thirty categories in eight themes were linked to make sense of the series of events leading to academic failure.

Results

One or more critical incidents commenced during the academic year, which led to possible resulting events. The students had poor attitudes, ineffective learning methods, health problems or stress. Students progressed to mid-year assessments and reacted differently to their results in the assessments. Afterwards, the students tried different types of attempts, and they still failed the end-of-year assessments. The general process of academic failure is illustrated in a diagram describing chronological events.

Conclusion

Academic failure may be explained by a series of events (and consequences) of what students experience and do and how they respond to their experiences. Preventing a preceding event may prevent students from suffering these consequences.
Preparedness for dental practice in Australia: a qualitative study on the experiences of final-year students and new graduates
Authors: Mariño Rodrigo , Manton David , Reid Katharine , Delany Clare
Published: May 2023

Background

Limited data exists regarding the perspectives of newly graduated dental practitioners (NGDPs) and final-year students (FYS) about their preparedness for dental practice. This information is crucial to inform developments in ongoing professional development for newly qualified dental practitioners and future reviews and development of accreditation standards, policies, and the professional competencies of newly qualified dental practitioners. Thus, the primary goal of this paper was to describe the perceptions of preparedness for dental practice of NGDPs and FYSs.

Methods

Individual semi-structured interviews were conducted between March and July 2020. All interviews were audiotaped, transcribed, and analysed using a thematic analysis.

Results

Eighteen NGDPs and four FYS from across Australia participated in the qualitative interviews. A strong theme from the data was that respondents believed they were well prepared for common challenges in dental practice and patient care. A second prominent theme was participants’ awareness of specific areas of limitation in their knowledge and specific skills including (list them). This data highlights a high level of self-awareness and potential for self-directed learning of NGDPs. It also provides specific content areas for future curriculum developers.

Conclusions

Newly graduated dental practitioner and final-year student participants were satisfied with the theoretical and evidence-based information in their formal learning and teaching activities to begin practicing as dental practitioners. In some areas, NGDPs felt underprepared, mostly attributed to limited clinical treatment exposure, and other contextual elements of clinical practice, and thought transitional support may be required. The research reinforces the value of seeking and learning from students’ and NGDPs’ perspectives.
Time optimization in primary care – chronic prescription cost
Authors: Leite-Costa Tiffany , Rodrigues Daniel , Sá Fernando , Cruz Correia Ricardo
Published: May 2023

Introduction

Time optimization is a common goal to most health information institutions. In several countries, chronic electronic renewal prescriptions were one of the main focuses when implementing information systems. In Portugal, Electronic Medical Prescription (PEM®) software is used for most electronic prescriptions. This study aims to quantify the time spent in chronic prescription renewal appointments (CPRA) in primary care and its impact in the Portuguese National Health System (SNS).

Methods

Eight general practitioners (GP) were included in the study during February 2022. The average duration of 100 CPRA was obtained. To determine the number of CPRA performed every year, a primary care BI-CSP® platform was used. Using Standard Cost Model and average medical doctor hourly rate in Portugal we estimated CPRA global costs.

Results

Each doctor spent on average 1:55 ± 01:07 min per CPRA. There were 8295 GP working in 2022. A total 635 561 CPRA were performed in 2020 and 774 346 in 2021. In 2020, CPRA costs ranged 303 088 ± 179 419€, and in 2021 that number increased to 369 272 ± 218 599€.

Conclusion

This is the first study to quantify CPRA’s real cost in Portugal. A PEM® software update would allow daily savings, ranging from 830€ (± 491€) in 2020 and 1011€ (± 598€) in 2021. That change could allow hiring 8 ± 5 GP in 2020 and 12 ± 7 in 2021.
An assessment of information needs and workflows for emergency service providers and caregivers of children with medical complexity
Authors: Honcoop Aubree , McCulloh Russell J. , Kerns Ellen , Lowndes Bethany , Simon Tiffany , McCawley Natalie , Flores Ricky , Clarke Martina
Published: May 2023

Background

The goal of Project Austin, an initiative to improve emergency care for rural children who are medically complex (CMC), is to provide an Emergency Information Form (EIF) to their parents/caregivers, to local Emergency Medical Services, and Emergency Departments. EIFs are standard forms recommended by the American Academy of Pediatrics that provide pre-planned rapid response instructions, including medical conditions, medications, and care recommendations, for emergency providers. Our objective is to describe the workflows and perceived utility of the provided emergency information forms (EIFs) in the acute medical management of CMC.

Methods

We sampled from two key stakeholder groups in the acute management of CMC: four focus groups with emergency medical providers from rural and urban settings and eight key informant interviews with parents/caregivers enrolled in an emergency medical management program for CMC. Transcripts were thematically analyzed in NVivo© by two coders using a content analysis approach. The thematic codes were combined into a codebook and revised the themes present through combining relevant themes and developing of sub-themes until they reached consensus.

Results

All parents/caregivers interviewed were enrolled in Project Austin and had an EIF. Emergency medical providers and parents/caregivers supported the usage of EIFs for CMC. Parents/caregivers also felt EIFs made emergency medical providers more prepared for their child. Providers identified that EIFs helped provide individualized care, however they were not confident the data was current and so felt unsure they could rely on the recommendations on the EIF.

Conclusion

EIFs are an easy way to engage parents, caregivers, and emergency medical providers about the specifics of a care for CMC during an emergency. Timely updates and electronic access to EIFs could improve their value for medical providers.
CAR-NKT cell therapy: a new promising paradigm of cancer immunotherapy
Authors: Hadiloo Kaveh , Tahmasebi Safa , Esmaeilzadeh Abdolreza
Published: May 2023

Today, cancer treatment is one of the fundamental problems facing clinicians and researchers worldwide. Efforts to find an excellent way to treat this illness continue, and new therapeutic strategies are developed quickly. Adoptive cell therapy (ACT) is a practical approach that has been emerged to improve clinical outcomes in cancer patients. In the ACT, one of the best ways to arm the immune cells against tumors is by employing chimeric antigen receptors (CARs) via genetic engineering. CAR equips cells to target specific antigens on tumor cells and selectively eradicate them. Researchers have achieved promising preclinical and clinical outcomes with different cells by using CARs. One of the potent immune cells that seems to be a good candidate for CAR-immune cell therapy is the Natural Killer-T (NKT) cell. NKT cells have multiple features that make them potent cells against tumors and would be a powerful replacement for T cells and natural killer (NK) cells. NKT cells are cytotoxic immune cells with various capabilities and no notable side effects on normal cells. The current study aimed to comprehensively provide the latest advances in CAR-NKT cell therapy for cancers.
Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials
Authors: Khalaji Amirmohammad , Behnoush Amir Hossein , Alilou Sanam , Rezaee Malihe , Peiman Soheil , Sahebkar Amirhossein
Published: May 2023

Background

Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs).

Methods

We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted.

Results

Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation.

Conclusion

Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.
Extracellular vesicles and COPD: foe or friend?
Authors: Wu Jiankang , Ma Yiming , Chen Yan
Published: May 2023

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease characterized by progressive airflow limitation. The complex biological processes of COPD include protein hydrolysis tissue remodeling, innate immune inflammation, disturbed host-pathogen response, abnormal cellular phenotype conversion, and cellular senescence. Extracellular vesicles (EVs) (including apoptotic vesicles, microvesicles and exosomes), are released by almost all cell types and can be found in a variety of body fluids including blood, sputum and urine. EVs are key mediators in cell-cell communication and can be used by using their bioactive substances (DNA, RNA, miRNA, proteins and other metabolites) to enable cells in adjacent and distant tissues to perform a wide variety of functions, which in turn affect the physiological and pathological functions of the body. Thus, EVs is expected to play an important role in the pathogenesis of COPD, which in turn affects its acute exacerbations and may serve as a diagnostic marker for it. Furthermore, recent therapeutic approaches and advances have introduced EVs into the treatment of COPD, such as the modification of EVs into novel drug delivery vehicles. Here, we discuss the role of EVs from cells of different origins in the pathogenesis of COPD and explore their possible use as biomarkers in diagnosis, and finally describe their role in therapy and future prospects for their application.
Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects
Authors: Nasiri Kamyar , Mohammadzadehsaliani Saman , Kheradjoo Hadis , Shabestari Alireza Mohammadzadeh , Eshaghizadeh Parisa , Pakmehr Azin , Alsaffar Marwa Fadhil , Al-Naqeeb Bashar Zuhair Talib , Yasamineh Saman , Gholizadeh Omid
Published: May 2023

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc.
CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn
Authors: Wang Jie , Yin Chengyu , Pan Yushuang , Yang Yunqin , Li Wei , Ni Huadong , Liu Boyu , Nie Huimin , Xu Ruoyao , Wei Huina , Zhang Yunwen , Li Yuanyuan , Hu Qimiao , Tai Yan , Shao Xiaomei , Fang Jianqiao , Liu Boyi
Published: May 2023

Background

Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients’ life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics.

Methods

The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice.

Results

CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5−/−) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5−/− mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice.

Conclusions

These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.
Health and economic implications of the ongoing coronavirus disease (COVID-19) pandemic on women and children in Africa
Authors: Yeboah Helena , Yaya Sanni
Published: May 2023

The coronavirus disease (COVID-19) pandemic continues to pose major health and economic challenges for many countries worldwide. Particularly for countries in the African region, the existing precarious health status resulting from weak health systems have made the impact of the pandemic direr. Although the number of the COVID-19 infections in Africa cannot be compared to that of Europe and other parts of the world, the economic and health ramifications cannot be overstated. Significant impacts of the lockdowns during the onset of the pandemic caused disruptions in the food supply chain, and significant declines in income which decreased the affordability and consumption of healthy diets among the poor and most vulnerable. Access and utilization of essential healthcare services by women and children were also limited because of diversion of resources at the onset of the pandemic, limited healthcare capacity, fear of infection and financial constraint. The rate of domestic violence against children and women also increased, which further deepened the inequalities among these groups. While all African countries are out of lockdown, the pandemic and its consequent impacts on the health and socio-economic well-being of women and children persist. This commentary discusses the health and economic impact of the ongoing pandemic on women and children in Africa, to understand the intersectional gendered implications within socio-economic and health systems and to highlight the need for a more gender-based approach in response to the consequences of the pandemic in the Africa region.
Predictive values of procalcitonin for coinfections in patients with COVID-19: a systematic review and meta-analysis
Authors: Wei Shanchen , Wang Lina , Lin Lianjun , Liu Xinmin
Published: May 2023

Objectives

To assess the ability of procalcitonin (PCT)—a promising marker for coinfections—to predict coinfections in patients with COVID-19.

Methods

In this systematic review and meta-analysis, PubMed, Embase, Web of Science, Cochrane, the China National Knowledge Infrastructure (CNKI), and Wanfang were searched to identify eligible studies (up to August 30, 2021). Articles that reported the predictive value of PCT for coinfections in patients with COVID-19 were included. Individual and pooled sensitivities and specificities were reported, and I2 was used to test heterogeneity. This study was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42021283344).

Results

Five studies involving a total of 2775 patients reported the predictive value of PCT for coinfections in patients with COVID-19. The sensitivity, specificity, and area under the curve of PCT in predicting coinfections in the pooled studies were 0.60 (95% CI 0.35–0.81, I2 = 88.85), 0.71 (95% CI 0.58–0.81, I2 = 87.82), and 0.72(95% CI 0.68–0.76) respectively.

Conclusions

Although PCT has limited predictive value for coinfections in patients with COVID-19, lower PCT levels seem to indicate a decreased probability of having a coinfection.
Automatic segmentation of vestibular schwannomas from T1-weighted MRI with a deep neural network
Authors: Wang Hesheng , Qu Tanxia , Bernstein Kenneth , Barbee David , Kondziolka Douglas
Published: May 2023

Background

Long-term follow-up using volumetric measurement could significantly assist in the management of vestibular schwannomas (VS). Manual segmentation of VS from MRI for treatment planning and follow-up assessment is labor-intensive and time-consuming. This study aims to develop a deep learning technique to fully automatically segment VS from MRI.

Methods

This study retrospectively analyzed MRI data of 737 patients who received gamma knife radiosurgery for VS. Treatment planning T1-weighted isotropic MR and manually contoured gross tumor volumes (GTV) were used for model development. A 3D convolutional neural network (CNN) was built on ResNet blocks. Spatial attenuation and deep supervision modules were integrated in each decoder level to enhance the training for the small tumor volume on brain MRI. The model was trained and tested on 587 and 150 patient data, respectively, from this institution (n = 495) and a publicly available dataset (n = 242). The model performance were assessed by the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), average symmetric surface (ASSD) and relative absolute volume difference (RAVD) of the model segmentation results against the GTVs.

Results

Measured on combined testing data from two institutions, the proposed method achieved mean DSC of 0.91 ± 0.08, ASSD of 0.3 ± 0.4 mm, HD95 of 1.3 ± 1.6 mm, and RAVD of 0.09 ± 0.15. The DSCs were 0.91 ± 0.09 and 0.92 ± 0.06 on 100 testing patients of this institution and 50 of the public data, respectively.

Conclusions

A CNN model was developed for fully automated segmentation of VS on T1-Weighted isotropic MRI. The model achieved good performance compared with physician clinical delineations on a sizeable dataset from two institutions. The proposed method potentially facilitates clinical workflow of radiosurgery for VS patient management.
Neural network and spline-based regression for the prediction of salivary hypofunction in patients undergoing radiation therapy
Authors: Smith Derek K. , Clark Haley , Hovan Allan , Wu Jonn
Published: May 2023

Background

This study leverages a large retrospective cohort of head and neck cancer patients in order to develop machine learning models to predict radiation induced hyposalivation from dose-volume histograms of the parotid glands.

Methods

The pre and post-radiotherapy salivary flow rates of 510 head and neck cancer patients were used to fit three predictive models of salivary hypofunction, (1) the Lyman-Kutcher-Burman (LKB) model, (2) a spline-based model, (3) a neural network. A fourth LKB-type model using literature reported parameter values was included for reference. Predictive performance was evaluated using a cut-off dependent AUC analysis.

Results

The neural network model dominated the LKB models demonstrating better predictive performance at every cutoff with AUCs ranging from 0.75 to 0.83 depending on the cutoff selected. The spline-based model nearly dominated the LKB models with the fitted LKB model only performing better at the 0.55 cutoff. The AUCs for the spline model ranged from 0.75 to 0.84 depending on the cutoff chosen. The LKB models had the lowest predictive ability with AUCs ranging from 0.70 to 0.80 (fitted) and 0.67 to 0.77 (literature reported).

Conclusion

Our neural network model showed improved performance over the LKB and alternative machine learning approaches and provided clinically useful predictions of salivary hypofunction without relying on summary measures.
Arthroscopic reconstruction of the medial patellofemoral ligament in skeletally immature patients using the modified sling procedure: a novel technique for MPFL reconstruction
Authors: Zhang Qingguo , Ying Liwei , Han Dawei , Ye Lingchao , Tung Tao-Hsin , Liang Junbo , Liu Peihong , Zhou Xiaobo
Published: May 2023

Background

Patellar dislocation is common in young people. Although isolated anatomic double-bundle reconstruction of the MPFL is a common and effective surgical treatment for patellofemoral instability, concerns about the risk of injury to the epiphysis remain.

Methods

A total of 21 children and adolescents (9 males, 12 females; mean age: 10.7 years; range: 8 to 13 years) with recurrent patella dislocation or symptomatic instability following a primary dislocation were enrolled in the study. In all patients, double-bundle medial patellofemoral ligament (MPFL) reconstruction and femoral sling procedure were performed under arthroscopy, using an anterior half peroneus longus tendon (AHPLT) autograft. Functional outcomes were evaluated preoperatively and during follow-ups based on Kujala and Lysholm scores. Radiological examinations including radiographs, 3D-CT, and MRI were performed pre- and post-operatively.

Results

Among two-year postoperative follow-up (range: 24–42 months) showed significant improvement in functional scores (p < 0.01). The Lysholm score increased from 68 (44.5) to 100 (0) and the Kujala score increased from 26 (34.5) to 100 (2) The patellar tilt angel improved significantly (p < 0.01) from 24.3° ± 10.4 preoperatively to 11.9° ± 7.0 postoperatively. MRIs performed 6- and 12-months post operation did not show any signs of dysfunction of the reconstructed MPFL or cartilage degeneration.

Study design

Case Series; Level of evidence, 4.

Conclusion

Arthroscopic reconstruction of the MPFL using the modified sling procedure is an effective procedure for the treatment of patellar instability in skeletally immature patients.
Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway
Authors: Wu Jianxin , Yu Lei , Liu Yi , Xiao Bing , Ye Xiaojian , Zhao Hong , Xi Yanhai , Shi Zhicai , Wang Weiheng
Published: May 2023

Objective

Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation.

Method

ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions.

Result

The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed.

Conclusion

Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.
Determining the relationship between over-care burden and coping styles, and resilience in mothers of children with autism spectrum disorder
Authors: Rasoulpoor Shabnam , Salari Nader , Shiani Amir , Khaledi-Paveh Behnam , Mohammadi Masoud
Published: May 2023

Background

Stress and over-care burden are problems for mothers of children with Autism Spectrum Disorder (ASD). Therefore, it seems necessary to evaluation of coping with stress according to the burden of care for these mothers. This study aimed to determine the relationship between care burden with coping styles and resilience of mothers of children with ASD.

Methods

The present study is a descriptive-analytical study performed on mothers of children with ASD in Kermanshah, Iran. Participants in the study were selected by convenience sampling. A Demographic questionnaire, Caregiver Burden Inventory (CBI), Connor-Davidson Resilience Scale (CD-RISC), and Coping strategies questionnaire (CSQ) were used for collecting data. Then it was analyzed through an independent t-test, ANOVA, and Pearson correlation test.

Results

The mean total score of the burden of care was 95.5 ± 9.1, resilience was 52.7 ± 8.7, and coping styles were 92.4 ± 8.4. Mothers of children with autism experience a severe burden of care and moderate levels of resiliency. There was also a significant negative correlation between the burden of care and resilience) p < 0.001, r = -0.536), but no significant correlation was found between burden of care and coping style) p = 0.937, r = -0.010).

Conclusion

According to the results of this study, it is necessary to pay more attention to the factors affecting resiliency. Also, considering the significant relationship between burden of care and resiliency, teaching strategies to increase resiliency can be used in the educational program for mothers with autistic children.
Fukushima study for Engaging people with type 2 Diabetes in Behaviour Associated Change (FEEDBACK): study protocol for a cluster randomised controlled trial
Authors: Rouyard Thomas , Endo Mei , Nakamura Ryota , Moriyama Michiko , Stanyon Maham , Kanke Satoshi , Nakamura Koki , Chen Cynthia , Hara Yasushi , Ii Masako , Kassai Ryuki
Published: May 2023

Background

The growing burden of type 2 diabetes mellitus (T2DM) and the rising cost of healthcare worldwide make it imperative to identify interventions that can promote sustained self-management behaviour in T2DM populations while minimising costs for healthcare systems. The present FEEDBACK study (Fukushima study for Engaging people with type 2 Diabetes in Behaviour Associated Change) aims to evaluate the effects of a novel behaviour change intervention designed to be easily implemented and scaled across a wide range of primary care settings.

Methods

A cluster randomised controlled trial (RCT) with a 6-month follow-up will be conducted to evaluate the effects of the FEEDBACK intervention. FEEDBACK is a personalised, multi-component intervention intended to be delivered by general practitioners during a routine diabetes consultation. It consists of five steps aimed at enhancing doctor-patient partnership to motivate self-management behaviour: (1) communication of cardiovascular risks using a ‘heart age’ tool, (2) goal setting, (3) action planning, (4) behavioural contracting, and (5) feedback on behaviour. We aim to recruit 264 adults with T2DM and suboptimal glycaemic control from 20 primary care practices in Japan (cluster units) that will be randomly assigned to either the intervention or control group. The primary outcome measure will be the change in HbA1c levels at 6-month follow-up. Secondary outcome measures include the change in cardiovascular risk score, the probability to achieve the recommended glycaemic target (HbA1c <7.0% [53mmol/mol]) at 6-month follow-up, and a range of behavioural and psychosocial variables. The planned primary analyses will be carried out at the individual level, according to the intention-to-treat principle. Between-group comparisons for the primary outcome will be analysed using mixed-effects models. This study protocol received ethical approval from the research ethics committee of Kashima Hospital, Fukushima, Japan (reference number: 2022002).

Discussion

This article describes the design of a cluster RCT that will evaluate the effects of FEEDBACK, a personalised, multicomponent intervention aimed at enhancing doctor-patient partnership to engage adults with T2DM more effectively in self-management behaviour.

Trial registration

The study protocol was prospectively registered in the UMIN Clinical Trials Registry (UMIN-CTR ID UMIN000049643 assigned on 29/11/2022). On submission of this manuscript, recruitment of participants is ongoing.
Analytical quality-by-design approach for development and validation of HPLC method for the simultaneous estimation of omarigliptin, metformin, and ezetimibe: application to human plasma and dosage forms
Authors: Magdy Galal , Al-enna Amira A. , Belal Fathalla , El-Domany Ramadan A. , Abdel-Megied Ahmed M.
Published: May 2023

A simple, selective, and sensitive RP-HPLC method was proposed for the simultaneous determination of two co-administered antidiabetic drugs (omarigliptin and metformin) with an anti-hyperlipidemic drug (ezetimibe) in a medicinally-recommended ratio of 2.5:50:1, respectively. The proposed procedure was optimized by adopting a quality-by-design approach. The influence of different factors on chromatographic responses was optimized by applying the two-level full factorial design (25). The optimum chromatographic separation was achieved using Hypersil BDS C18 column at 45 °C, and the mobile phase pumped isocratically composed of methanol: potassium dihydrogen phosphate buffer (6.6 mM; pH 7, 67:33% v/v) at a flow rate of 0.814 mL/min using 235 nm as a detection wavelength. The developed method was capable of separating this novel mixture in less than 8 min. The calibration plots of omarigliptin, metformin, and ezetimibe showed acceptable linearity over the ranges of 0.2-2.0, 0.5–25.0, and 0.1-2.0 µg/mL with quantitation limits of 0.06, 0.50, and 0.06 µg/mL, respectively. The proposed method was successfully applied to determine the studied drugs in their commercial tablets with high % recoveries (96.8-102.92%) and low % RSD values (less than 2%). The applicability of the method was extended to the in-vitro assay of the drugs in spiked human plasma samples with high % recoveries (94.3-105.7%). The suggested method was validated in accordance with ICH guidelines.
Comprehensive de novo mutation discovery with HiFi long-read sequencing
Authors: Kucuk Erdi , van der Sanden Bart P. G. H. , O’Gorman Luke , Kwint Michael , Derks Ronny , Wenger Aaron M. , Lambert Christine , Chakraborty Shreyasee , Baybayan Primo , Rowell William J. , Brunner Han G. , Vissers Lisenka E. L. M. , Hoischen Alexander , Gilissen Christian
Published: May 2023

Background

Long-read sequencing (LRS) techniques have been very successful in identifying structural variants (SVs). However, the high error rate of LRS made the detection of small variants (substitutions and short indels < 20 bp) more challenging. The introduction of PacBio HiFi sequencing makes LRS also suited for detecting small variation. Here we evaluate the ability of HiFi reads to detect de novo mutations (DNMs) of all types, which are technically challenging variant types and a major cause of sporadic, severe, early-onset disease.

Methods

We sequenced the genomes of eight parent–child trios using high coverage PacBio HiFi LRS (~ 30-fold coverage) and Illumina short-read sequencing (SRS) (~ 50-fold coverage). De novo substitutions, small indels, short tandem repeats (STRs) and SVs were called in both datasets and compared to each other to assess the accuracy of HiFi LRS. In addition, we determined the parent-of-origin of the small DNMs using phasing.

Results

We identified a total of 672 and 859 de novo substitutions/indels, 28 and 126 de novo STRs, and 24 and 1 de novo SVs in LRS and SRS respectively. For the small variants, there was a 92 and 85% concordance between the platforms. For the STRs and SVs, the concordance was 3.6 and 0.8%, and 4 and 100% respectively. We successfully validated 27/54 LRS-unique small variants, of which 11 (41%) were confirmed as true de novo events. For the SRS-unique small variants, we validated 42/133 DNMs and 8 (19%) were confirmed as true de novo event. Validation of 18 LRS-unique de novo STR calls confirmed none of the repeat expansions as true DNM. Confirmation of the 23 LRS-unique SVs was possible for 19 candidate SVs of which 10 (52.6%) were true de novo events. Furthermore, we were able to assign 96% of DNMs to their parental allele with LRS data, as opposed to just 20% with SRS data.

Conclusions

HiFi LRS can now produce the most comprehensive variant dataset obtainable by a single technology in a single laboratory, allowing accurate calling of substitutions, indels, STRs and SVs. The accuracy even allows sensitive calling of DNMs on all variant levels, and also allows for phasing, which helps to distinguish true positive from false positive DNMs.
Long-lasting complete remission in a patient with systemic metastases of recurrent breast cancer treated with cyclin-dependent kinases 4/6 inhibitors: a case report
Authors: Yoneto Toshihiko , Hasumi Kenichiro , Takahashi Nobukazu , Seki Nastuki , Takeda Yasutaka , Yoshimoto Takayuki
Published: May 2023

Background

The prognosis for recurrence cases of hormone receptor-positive HER2-negative breast cancer remains poor, and treatment strategies that emphasize quality of life have often been chosen, with few physicians aiming for a cure. Our objective is to assess the validity of such current treatment strategies.

Case presentation

A 74-year-old Asian woman with multiple lung and liver metastases after local recurrence of breast cancer was treated with two different cyclin-dependent kinases 4/6 inhibitors sequentially in combination with endocrine therapy. Flow cytometric analysis of the patient’s peripheral blood mononuclear cells was also performed to evaluate the host’s immune status. Complete remission was achieved without cytotoxic agents and the patient remains disease free to this day, 6 years after the initial relapse. Additionally, no increase in the population of the immunosenescent T cells with a phenotype of CD8+CD28− was observed in the patient’s peripheral blood mononuclear cells, suggesting that the immune system was well maintained.

Conclusions

We present this case study to develop new treatment strategies for recurrent breast cancer that is not only bound to misinterpretations of the Hortobagyi algorithm, but also aim for a cure with noncytotoxic agents to maintain the host’s immune system and early detection of recurrence.
A forged ‘chimera’ including the second specimen of the protostegid sea turtle Santanachelys gaffneyi and shell parts of the pleurodire Araripemys from the Lower Cretaceous Santana Group of Brazil
Authors: Scheyer Torsten M. , Oliveira Gustavo R. , Romano Pedro S. R. , Bastiaans Dylan , Falco Lisa , Ferreira Gabriel S. , Rabi Márton
Published: May 2023

Fossils of Cretaceous sea turtles adapted to an open marine lifestyle remain rare finds to date. Furthermore, the relationships between extant sea turtles, chelonioids, and other Mesozoic marine turtles are still contested, with one key species being Santanachelysgaffneyi Hirayama, 1998, long considered the earliest true sea turtle. The species is an Early Cretaceous member of Protostegidae, a controversial clade either placed within or closely related to Chelonioidea or, alternatively, along the stem lineage of hidden-neck turtles (Cryptodira) and representing an independent open marine radiation. Santanachelysgaffneyi is one of the most completely preserved early protostegids and is therefore critical for establishing the global phylogenetic position of the group. However, the single known specimen of this taxon is yet to be described in detail. Here we describe a second specimen of Santanachelysgaffneyi from its type horizon, the Romualdo Formation (late Aptian) of the Santana Group of the Araripe basin, NE Brazil. The skeletal elements preserved include the posterior part of the skull, neck vertebrae, shoulder girdle, anterior-most and left/central part of the carapace with few peripherals, and plastron lacking most of the hyoplastra. The remaining part of the carapace was apparently completed by fossil dealers using an anterior part of the pleurodiran Araripemydidae, tentatively identified as a shell portion of cf. Araripemysbarretoi, a more common Santana fossil turtle, among other indeterminate turtle shell fragments. The purpose of this paper is to report the repatriation of the specimen to Brazil and to provide a preliminary description.
Prehabilitation for patients with colorectal cancer: a snapshot of current daily practice in Dutch hospitals
Authors: Molenaar Charlotte J. L. , Reudink Muriël , Sabajo Charissa R. , Janssen Loes , Roumen Rudi M. H. , Klaase Joost M. , Slooter Gerrit D.
Published: May 2023

Background

Multimodal prehabilitation programmes are increasingly being imbedded in colorectal cancer (CRC) pathways to enhance the patient’s recovery after surgery. However, there is no (inter)national consensus on the content or design of such a programme. This study aimed to evaluate the current practice and opinion regarding preoperative screening and prehabilitation for patients undergoing surgery for CRC throughout the Netherlands.

Methods

All regular Dutch hospitals offering colorectal cancer surgery were included. An online survey was sent to one representative colorectal surgeon per hospital. Descriptive statistics were used for analyses.

Results

Response rate was 100% (n = 69). Routine preoperative screening of patients with CRC for frailty, diminished nutritional status and anaemia was the standard of care in nearly all Dutch hospitals (97%, 93% and 94%, respectively). Some form of prehabilitation was provided in 46 hospitals (67%) of which more than 80% addressed nutritional status, frailty, physical status and anaemia. All but two of the remaining hospitals were willing to adopt prehabilitation. The majority of the hospitals offered prehabilitation to specific subgroups of patients with CRC, such as the elderly (41%), the frail (71%) or high-risk patients (57%). There was high variability in the setting, design and content of the prehabilitation programmes.

Conclusions

Whereas preoperative screening is sufficiently incorporated in Dutch hospitals, standardised enhancement of the patient’s condition in the context of multimodal prehabilitation seems to be challenging. This study presents an overview of current clinical practice in the Netherlands. Uniform clinical prehabilitation guidelines are vital to diminish heterogeneity in programmes and to produce useful data to enable a nationwide implementation of an evidence-based prehabilitation programme.
Microtubule acetylation dyshomeostasis in Parkinson’s disease
Authors: Naren Padmashri , Samim Khan Sabiya , Tryphena Kamatham Pushpa , Vora Lalitkumar K. , Srivastava Saurabh , Singh Shashi Bala , Khatri Dharmendra Kumar
Published: May 2023

The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule (MT)-mediated axonal transport system. This mechanistically regulated system delivers cargos (proteins, mRNAs and organelles such as mitochondria) back and forth from the soma to the synapse. Motor proteins like kinesins and dynein mechanistically regulate polarized anterograde (from the soma to the synapse) and retrograde (from the synapse to the soma) commute of the cargos, respectively. Proficient axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications (PTMs) of α- and β-tubulin heterodimers, core components constructing the MTs. Occurring within the lumen of MTs, K40 acetylation of α-tubulin via α-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible, which in turn promotes their lifespan. The movement of various motor proteins, including kinesin-1 (responsible for axonal mitochondrial commute), is enhanced by this PTM, and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions, including Alzheimer’s disease and Parkinson’s disease (PD). PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation levels. Although the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question, our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in PD. The enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly explored. Moving towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it.

Graphical abstract