bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions
Authors: Proust Alizé , Queval Christophe J. , Harvey Ruth , Adams Lorin , Bennett Michael , Wilkinson Robert J. 
Published: August 2023

Abstract
Background
Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear.

Methods
We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood–brain barrier model were infected with the wild-type form of SARS-CoV-2, Alpha, Beta, Delta, Eta, or Omicron (BA.1) variants at various MOI. Cells and supernatant were used to evaluate cell susceptibility to the virus using a microscopic assay as well as effects of infection on (i) cell metabolic activity using a colorimetric MTS assay; (ii) viral cytopathogenicity using the xCELLigence system; (iii) extracellular glutamate concentration by fluorometric assay; and (iv) modulation of blood–brain barrier permeability.

Results
We demonstrate that productive infection of brain cells is SARS-CoV-2 variant dependent and that all the variants induce stress to CNS cells. The wild-type virus was cytopathic to all cell types except astrocytes, whilst Alpha and Beta variants were only cytopathic for pericytes, and the Omicron variant cytopathic for endothelial cells and pericytes. Lastly wild-type virus increases blood–brain barrier permeability and all variants, except Beta, modulate extracellular glutamate concentration, which can lead to excitotoxicity or altered neurotransmission.

Conclusions
These results suggest that SARS-CoV-2 is neurotropic, with deleterious consequences for the blood–brain barrier integrity and central nervous system cells, which could underlie neurological disorders following SARS-CoV-2 infection.
Feasibility of force myography for the direct control of an assistive robotic hand orthosis in non-impaired individuals
Authors: Gantenbein Jessica , Ahmadizadeh Chakaveh , Heeb Oliver , Lambercy Olivier , Menon Carlo 
Published: August 2023

Abstract
Background
Assistive robotic hand orthoses can support people with sensorimotor hand impairment in many activities of daily living and therefore help to regain independence. However, in order for the users to fully benefit from the functionalities of such devices, a safe and reliable way to detect their movement intention for device control is crucial. Gesture recognition based on force myography measuring volumetric changes in the muscles during contraction has been previously shown to be a viable and easy to implement strategy to control hand prostheses. Whether this approach could be efficiently applied to intuitively control an assistive robotic hand orthosis remains to be investigated.

Methods
In this work, we assessed the feasibility of using force myography measured from the forearm to control a robotic hand orthosis worn on the hand ipsilateral to the measurement site. In ten neurologically-intact participants wearing a robotic hand orthosis, we collected data for four gestures trained in nine arm configurations, i.e., seven static positions and two dynamic movements, corresponding to typical activities of daily living conditions. In an offline analysis, we determined classification accuracies for two binary classifiers (one for opening and one for closing) and further assessed the impact of individual training arm configurations on the overall performance.

Results
We achieved an overall classification accuracy of 92.9% (averaged over two binary classifiers, individual accuracies 95.5% and 90.3%, respectively) but found a large variation in performance between participants, ranging from 75.4 up to 100%. Averaged inference times per sample were measured below 0.15 ms. Further, we found that the number of training arm configurations could be reduced from nine to six without notably decreasing classification performance.

Conclusion
The results of this work support the general feasibility of using force myography as an intuitive intention detection strategy for a robotic hand orthosis. Further, the findings also generated valuable insights into challenges and potential ways to overcome them in view of applying such technologies for assisting people with sensorimotor hand impairment during activities of daily living.
Withania somnifera extracts induced attenuation of HIV-1: a mechanistic approach to restrict viral infection
Authors: Jadaun Pratiksha , Harshithkumar R , Gaikwad Shraddha Y , Seniya Chandrabhan , Borse Swapnil , Gawai Ashish A , Chavan-Gautam Preeti , Tillu Girish , Mukherjee Anupam 
Published: August 2023

Abstract
Background
Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules.

Methods
The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes.

Results
The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies.

Conclusions
Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.
A nomogram model based on the combination of the systemic immune-inflammation index, body mass index, and neutrophil/lymphocyte ratio to predict the risk of preoperative deep venous thrombosis in elderly patients with intertrochanteric femoral fracture: a retrospective cohort study
Authors: Zeng Guowei , Li Xu , Li Wencai , Wen Zhijia , Wang Shenjie , Zheng Shaowei , Lin Xia , Zhong Haobo , Zheng Jianping , Sun Chunhan 
Published: August 2023

Abstract
Objectives
Deep vein thrombosis (DVT) has been considered as a frequent and serious consequence of intertrochanteric femoral fractures in the elderly. Several negative repercussions of DVT can be considerably mitigated by its timely recognition and treatment. The current work was aimed at exploring the factors independently predicting DVT among cases suffering from intertrochanteric femoral fractures and validate their predictive usefulness in diagnosing DVT.

Methods
Between April 2017 and July 2022, clinical information from 209 cases showing preoperative DVT for femoral intertrochanteric fractures were retrospectively evaluated. In patients with femoral intertrochanteric fractures, logistic regression analysis with a backward stepwise method was adopted for detecting independent predictors for the diagnosis of preoperative DVT. Using multivariate logistic regression, a nomogram prediction model was developed and verified with the testing group.

Results
According to multivariate logistic regression model, body mass index (BMI) (OR 0.79, 95% CI 0.63–0.99, P = 0.042), neutrophil/lymphocyte ratio (NLR) (OR 7.29, 95% CI 1.53, 34.64, P = 0.0012), and systemic immune-inflammation index (SII) (OR 6.61, 95% CI 2.35, 18.59, P = 0.001) were independent predictors for DVT before surgery among cases developing intertrochanteric femoral fracture. AUC values were 0.862 and 0.767 for training and testing groups, separately, while their mean errors in the calibration curve were 0.027 and 0.038 separately. Decision curve analysis (DCA) curve revealed a high value of clinical application for both groups.

Conclusion
Upon admission, BMI, NLR, and SII are independent predictors of DVT before surgery among cases developing intertrochanteric femoral fractures. Additionally, the nomogram based on the BMI, NLR, and SII can assist clinicians in determining if preventive and symptomatic therapies are required to improve DVT prognosis and reduce its associated mortality.
Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction
Authors: Zhang Zhi-yu , Shi Wei-li , Bai Wen-bin , Meng Ling-yu , Meng Qing-yang , Wang Jian-quan , Wang Cheng 
Published: August 2023

Abstract
Background
The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR.

Methods
A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS).

Results
No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group.

Conclusion
Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group.
Level of evidence Level III.
A novel animal model of osteonecrosis of the femoral head based on 3D printing technology
Authors: Li Yiyang , Zhang Jiewen , Zhao Yiwei , Tian Run , Yang Pei 
Published: August 2023

Abstract
Background
Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic condition characterized by the disruption of blood supply to the femoral head, leading to ischemia of internal tissues, subchondral bone fractures, necrosis, and eventual collapse of the weight-bearing portion of the femoral head. This condition results in severe functional impairment, pain, and even disability of the hip joint. Existing animal models of ONFH have limitations in replicating the natural disease progression accurately. Thus, there is a critical need to develop a novel animal model capable of better simulating localized pressure on the human femoral head to facilitate ONFH-related research.

Methods
In this study, we present a novel approach for modeling ONFH, which involves integrating stress factors into the modeling process through the utilization of 3D printing technology and principles of biomechanics. A total of 36 animals were randomly assigned to six groups, where they received either the novel modeling technique or the traditional hormone induction method. Subsequently, an 8-week treatment period was implemented, followed by conducting micro-CT scans and histological evaluations to assess tissue outcomes.

Results
The study evaluated the cytotoxicity of the material used in the new model, and it was observed that the material did not exhibit any cytotoxic effects on cells. Additionally, the novel model successfully replicated the pathological features of ONFH, including femoral head collapse, along with a substantial presence of empty bone lacunae, cartilage defects, and subchondral bone fractures in the subchondral bone region.

Conclusion
In conclusion, our study provides evidence that the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem.
A systematic review of the research progress of traditional Chinese medicine against pulmonary fibrosis: from a pharmacological perspective
Authors: Qin Shanbo , Tan Peng , Xie Junjie , Zhou Yongfeng , Zhao Junning 
Published: August 2023

AbstractPulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the lung tissue structure, severely affecting respiratory function and posing a serious threat to human health. Currently, glucocorticoids and immunosuppressants are the main drugs used in the clinical treatment of pulmonary fibrosis, but their efficacy is limited and they can cause serious adverse effects. Traditional Chinese medicines have important research value and potential for clinical application in anti-pulmonary fibrosis. In recent years, more and more scientific researches have been conducted on the use of traditional Chinese medicine to improve or reduce pulmonary fibrosis, and some important breakthroughs have been made. This review paper systematically summarized the research progress of pharmacological mechanism of traditional Chinese medicines and their active compounds in improving or reducing pulmonary fibrosis. We conducted a systematic search in several main scientific databases, including PubMed, Web of Science, and Google Scholar, using keywords such as idiopathic pulmonary fibrosis, pulmonary fibrosis, interstitial pneumonia, natural products, herbal medicine, and therapeutic methods. Ultimately, 252 articles were included and systematically evaluated in this analysis. The anti-fibrotic mechanisms of these traditional Chinese medicine studies can be roughly categorized into 5 main aspects, including inhibition of epithelial-mesenchymal transition, anti-inflammatory and antioxidant effects, improvement of extracellular matrix deposition, mediation of apoptosis and autophagy, and inhibition of endoplasmic reticulum stress. The purpose of this article is to provide pharmaceutical researchers with information on the progress of scientific research on improving or reducing Pulmonary fibrosis with traditional Chinese medicine, and to provide reference for further pharmacological research.
Barriers to prophylactic treatment among patients with haemophilia A in Shandong Province, China: a qualitative study
Authors: Liu Ziyu , Feng Junchao , Fang Yunhai , Cheng Yan , Li Shunping 
Published: August 2023

Abstract
Background
Haemophilia A is a rare, hereditary haemorrhagic disease that manifests as induced spontaneous bleeding and leads to disability or premature death in severe cases. Prophylactic treatment is optimal for patients to prevent uncontrolled bleeding and reduce the severity of the injury. However, little is known about the use of prophylactic treatment among patients with haemophilia A in China, especially barriers that predispose them to low or non-adherence. In this study, we explore the barriers to the prophylactic treatment of patients with haemophilia A.

Method
We used personal interviews and focus groups to collect the data and analysed the data through thematic analysis. Purposive sampling was employed to recruit our participants. We continued recruiting participants until data saturation was reached from the thematic analysis. Ultimately, we obtained 37 participants, among whom 19 participated in personal interviews and 18 participated in focus groups (i.e., 3 focus groups with 6 participants each).

Results
Three themes and nine subthemes were identified from the thematic analysis. Nine subthemes (i.e., perceived barriers) emerged from the analysis, which were further clustered into three themes: (1) poor primary health care, (2) inadequate financial support, and (3) a lack of patient-centred care.

Conclusion
The findings presented in this descriptive qualitative study offer a unique view of Chinese patients with haemophilia A and their barriers to prophylactic treatment. Our findings not only provide an in-depth understanding of barriers to prophylactic treatment encountered by Chinese patients with haemophilia A but also address the urgent need to strengthen primary care, provide adequate financial support, and establish patient-centred care for these suffering patients.
How to START? Four pillars to optimally begin your orphan drug development
Authors: Jonker Anneliene Hechtelt , Batista Liliana , Gabaldo Michela , Hivert Virginie , Ardigo Diego ,   on behalf of the IRDiRC ODDG TF and IRDiRC TSC
Published: August 2023

AbstractDrug development is a complex, resource intensive and long process in any disease area, and developing medicines to treat rare diseases presents even more challenges due to the small patient populations, often limited disease knowledge, heterogeneous clinical manifestations, and disease progression. However, common to all drug development programs is the need to gather as much information as possible on both the disease and the patients’ needs ahead of the development path definition. Here, we propose a checklist named START, a tool that provides an overview of the key pillars to be considered when starting an orphan drug development: STakeholder mapping, Available information on the disease, Resources, and Target patient value profile. This tool helps to build solid foundations of a successful patient-centered medicines development program and guides different types of developers through a set of questions to ask for guidance through the starting phase of a rare disease therapeutic pathway.
Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 Annual Meeting
Authors: Zhao Juanjuan , Ren Quan , Liu Xinyuan , Guo Xiangqian , Song Yongping 
Published: August 2023

AbstractSeveral bispecific antibodies (bsAbs) targeting BCMA, GPRC5D, and FcRH5 are in clinical trials for heavily pretreated multiple myeloma (MM) patients. Teclistamab was approved for relapsed/refractory MM therapy in 2022, while elranatamab, linvoseltamab, F182112, talquetamab, and cevostamab are currently undergoing clinical trials. This study summarizes several latest reports on bsAbs for the treatment of MM from the ASCO 2023 Annual Meeting.
O-RADS combined with contrast-enhanced ultrasound in risk stratification of adnexal masses
Authors: Shi Yanyun , Li Huan , Wu Xiuhua , Li Xiaoqin , Yang Min 
Published: August 2023

Abstract
Background
Ovarian-Adnexal Reporting and Data System (O-RADS) for ultrasound is a lexicon and risk stratification system that includes all risk categories and relevant management recommendation. It has high sensitivity in diagnosing malignant adnexal tumors, but the specificity is lower.

Objective
To explore the value of O-RADS combined with contrast-enhanced ultrasound (CEUS) in risk stratification of adnexal masses.

Methods
A retrospective study was performed on 85 patients with 100 adnexal masses that preoperatively underwent conventional ultrasound as well as CEUS examination and obtained the postoperative pathological results. The masses were classified into O-RADS2, 3, 4, and 5 by conventional ultrasound. After contrast enhancement, the classification of O-RADS was adjusted according to CEUS imaging features. The O-RADS 2 and 3 lesions with suspected malignant features like irregular blood vessels or internal inhomogeneous hyperenhancement were upgraded to O-RADS 4, and the O-RADS 4 lesions with the above features were upgraded to O-RADS 5. The O-RADS 4 lesions with suspicious benign angiographic features like a regular vessel, interior hypoenhancement or non-enhancement were downgraded to O-RADS 3; the O-RADS 5 lesions with rim ring-enhancement and interior non-enhancement were downgraded to O-RADS 3. The sensitivity, specificity, accuracy, PPV, NPV, and AUC of the two methods were compared, taking pathological results as the gold standard.

Results
The sensitivity, specificity, accuracy, PPV, NPV, and AUC of O-RADS and O-RADS combined with CEUS in the diagnosis of malignant adnexal tumors were 96.6%, 66.2%, 75.0%, 53.8%, 97.9%, 0.910 and 96.6%, 91.5%, 93.0%, 82.4%, 98.5%, 0.962, respectively. The specificity, accuracy, PPV, and AUC of O-RADS combined with CEUS were considerably higher than those of O-RADS (P < 0.01). Furthermore, both methods had excellent sensitivity and NPV but there were no significant differences between them(P > 0.05).

Conclusion
Combination of O-RADS and CEUS can significantly improve the specificity and PPV in diagnosing malignant adnexal tumors. It seems promising in the clinical application of risk stratification of adnexal masses.