bluuebunny/crossref_metadata_2025_split huggingface dataset:
The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009–2021
Authors: Li Chen , Hao Jun , Zheng Yitian , Wang Chuangshi , Yang Jie , Wang Wenyao , Zhang Kuo , Shao Chunli , Hui Wen , Wang Jiancheng , Li Wei , Tang Yi-Da 
Published: April 2023

Abstract
Background
Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021.

Methods
The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution.

Results
A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution.

Conclusions
Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.
Cardiometabolic risk indicators in individuals with bipolar disorders: a replication study
Authors: Najar Hemen , Karanti Alina , Pålsson Erik , Landén Mikael 
Published: April 2023

Abstract
Objectives
We recently conducted the first longitudinal study comparing cardiometabolic risk indicators (CMRIs) between a cohort of individuals with bipolar disorders (BDs) and controls from the general population. Here, we sought to validate the findings in that study using an independent case-control sample.

Methods
We used data from the St. Göran project’s Gothenburg cohort. The BDs group and the control group were examined at baseline and after a median of eight and seven years, respectively. Data collection occurred between March 2009 and June 2022. We used multiple imputation to handle missing data and linear mixed effects model to examine the annual change in CMRIs over the study period.

Results
The baseline cohort included 407 individuals with BDs (mean age 40 years, 63% women) and 56 controls (mean age 43 years, 54% women). Of those, 63 persons with BDs and 42 controls participated at follow-up. At baseline, individuals with BDs had significantly higher mean values of body mass index (β = 0.14, p = 0.003) than controls. Over the study period, the difference in average annual change between the patient and the control group indicated an increase in patients relative to controls in waist-to-hip ratio (0.004 unit/year, p = 0.01), diastolic (0.6 mm Hg/year, p = 0.048), and systolic (0.8 mm Hg/year, p = 0.02) blood pressure.

Conclusions
This study replicated the main findings from our previous study and showed that central obesity and measures of blood pressure worsened over a relatively short time in individuals with BDs relative to controls. It is vital for clinicians to monitor CMRIs in persons with BDs and to be proactive in preventing cardiometabolic diseases in this high-risk group.
The experience and influence of fear after anterior cruciate ligament reconstruction: an interview study with young athletes
Authors: Kvist Joanna , Bengtsson Johanna , Lundqvist Carolina 
Published: April 2023

AbstractBackgroundDespite good physical function, many athletes do not return to sports after an anterior cruciate ligament reconstruction (ACLR). One important reason for this is fear of new injury. The aim of this study was to investigate young athletes’ experiences of knee-related fear after an ACLR and how they perceive this fear to affect them in their sporting and everyday life.MethodsA qualitative interview study was conducted, using semi-structured interviews. Athletes who were active in contact or pivoting sport before an ACL injury, with the goal of returning to the same sport and who scored highly on fear of new injury at six months post-ACLR, were asked to participate. Ten athletes (six women and four men, aged 17–25 years), were interviewed by an independent researcher, 7–9 months after ACLR. Content analysis employing an abductive approach was used.ResultsThe analysis resulted in three categories with associated subcategories: 1. The expressions of fear; (i) reason for fear, (ii) changes in fear over time, and (iii) injury situation. 2. Reactions, consequences, and adaptations; (i) reactions, (ii) behavioural adaptation and influence on rehabilitation and daily life, (iii) present consequences, and (iv) consequences for the future. 3. Fear and adaptations related to returning to sports; (i) fear related to returning to sports and, (ii) adaptations in sports and life due to fear. Fear was described in broad and complex ways, with fear of a new injury being expressed as one of several aspects. Various reasons (e.g., seeing others getting injured in the past, previous experience of injury, failed rehabilitation, perceived knee instability) were given to explain the fear, and athletes reacted both physically and mentally to fear. Both positive and negative adaptations to fear were described, in both daily life and sports.ConclusionThe results contribute to an increased understanding of fear as an essential psychological factor to consider during rehabilitation and leaves the way open for research to investigate how physiotherapists can work to manage fear better among ACLR patients.
Validation study of “Santé-Cerveau”, a digital tool for early cognitive changes identification
Authors: Lesoil Constance , Bombois Stéphanie , Guinebretiere Octave , Houot Marion , Bahrami Mahsa , Levy Marcel , Genthon Rémy , Bozon Frédérique , Jean-Marie Heidy , Epelbaum Stéphane , Foulon Pierre , Villain Nicolas , Dubois Bruno 
Published: April 2023

Abstract
Background
There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability.

Methods
Three groups were constituted including 65 elderly Controls, 64 patients with neurodegenerative diseases (NDG): 50 AD and 14 non-AD, and 20 post-COVID-19 patients. The minimum MMSE score for inclusion was 20. Association between computerized SCD-T cognitive tests and their standard equivalent was assessed using Pearson's correlation coefficients. Two algorithms (a simple clinician-guided algorithm involving the 5-WT and the NCT; and a machine learning classifier based on 8 scores from the SCD-T tests extracted from a multiple logistic regression model, and data from the SCD-T questionnaires) were evaluated. The acceptability of SCD-T was investigated through a questionnaire and scale.

Results
AD and non-AD participants were older (mean ± standard deviation (SD): 72.61 ± 6.79 vs 69.91 ± 4.86 years old, p = 0.011) and had a lower MMSE score (Mean difference estimate ± standard error: 1.74 ± 0.14, p < 0.001) than Controls; post-COVID-19 patients were younger than Controls (mean ± SD: 45.07 ± 11.36 years old, p < 0.001). All the computerized SCD-T cognitive tests were significantly associated with their reference version. In the pooled Controls and NDG group, the correlation coefficient was 0.84 for verbal memory, -0.60 for executive functions, and 0.72 for global intellectual efficiency. The clinician-guided algorithm demonstrated 94.4% ± 3.8% sensitivity and 80.5% ± 8.7% specificity, and the machine learning classifier 96.8% ± 3.9% sensitivity and 90.7% ± 5.8% specificity. The acceptability of SCD-T was good to excellent.

Conclusions
We demonstrate the high accuracy of SCD-T in screening cognitive disorders and its good acceptance even in individuals with prodromal and mild dementia stages. SCD-T would be useful in primary care to faster refer subjects with significant cognitive impairment (and limit unnecessary referrals) to specialized consultation, improve the AD care pathway and the pre-screening in clinical trials.
Several Nocardia abcessus bronchiolitis in a patient treated with inhaled corticosteroids: a case report
Authors: Cascarano Estelle , Frappa Murielle , Degano Bruno , Pelloux Isabelle , Saint-Raymond Christel , Gheerbrant Hubert 
Published: April 2023

AbstractNocardiosis is a disease that mainly affects immunocompromised patients. Inhaled corticosteroids (ICS) are standard of care for asthma. This treatment can induce respiratory infections but no case of bronchiolitis nocardiosis have been described so far. A 58-year-old man, with history of controlled moderate allergic asthma, develop an increased cought in the last two years associated with dyspnea on exertion. Within two months, although ICS were increased to high doses, symptoms worsened due to a severe obstructive ventilatory disorder as revealed by pulmonary function tests (PFT). Small-scale lesions (< 10%) were found on chest computed tomography (CT). A bronchoalveolar lavage (BAL) found Nocardia abcessus. After six months of Sulfamethoxazole/Trimethoprim, PFT results improved and chest CT became completely normal. We therefore present the case of a bronchiolitis nocardiosis with several bronchial syndrome and the only immunosuppressive factor found were ICS.
Education and training in radiation protection in Europe: results from the EURAMED Rocc-n-Roll project survey
Authors: Santos Joana , Foley Shane , Andersson Jonas , Figueiredo João Paulo , Hoeschen Christoph , Damilakis John , Frija Guy , Alves Francisco , Riklund Katrine , Rainford Louise , Nestle Ursula , McNulty Jonathan , Bacher Klaus , Hierath Monika , Paulo Graciano 
Published: April 2023

Abstract
Purpose
To analyse the existing radiation protection (RP) education and training (E&T) capabilities in the European Union and identify associated needs, problems and challenges.

Method
An online survey was disseminated via the EURAMED Rocc-n-Roll consortium network and prominent medical societies in the field of radiological research. The survey sections analyse the RP E&T during undergraduate, residency/internship and continuous professional development; RP E&T problems and legal implementation. Differences were analysed by European geographic regions, profession, years of professional experience and main area of practice/research.

Results
The majority of the 550 respondents indicated that RP topics are part of undergraduate curricula in all courses for their profession and country (55%); however, hands-on practical training is not included according to 30% of the respondents. The lack of E&T, practical aspects in current E&T, and mandatory continuing E&T were considered the major problems. The legal requirement that obtained higher implementation score was the inclusion of the practical aspects of medical radiological procedures on education (86%), and lower score was obtained for the inclusion of RP E&T on medical and dental school curriculums (61%).

Conclusions
A heterogeneity in RP E&T during undergraduate, residency/internship and continuous professional development is evident across Europe. Differences were noted per area of practice/research, profession, and European geographic region. A large variation in RP E&T problem rating was also obtained.
Topological data analysis in medical imaging: current state of the art
Authors: Singh Yashbir , Farrelly Colleen M. , Hathaway Quincy A. , Leiner Tim , Jagtap Jaidip , Carlsson Gunnar E. , Erickson Bradley J. 
Published: April 2023

AbstractMachine learning, and especially deep learning, is rapidly gaining acceptance and clinical usage in a wide range of image analysis applications and is regarded as providing high performance in detecting anatomical structures and identification and classification of patterns of disease in medical images. However, there are many roadblocks to the widespread implementation of machine learning in clinical image analysis, including differences in data capture leading to different measurements, high dimensionality of imaging and other medical data, and the black-box nature of machine learning, with a lack of insight into relevant features. Techniques such as radiomics have been used in traditional machine learning approaches to model the mathematical relationships between adjacent pixels in an image and provide an explainable framework for clinicians and researchers. Newer paradigms, such as topological data analysis (TDA), have recently been adopted to design and develop innovative image analysis schemes that go beyond the abilities of pixel-to-pixel comparisons. TDA can automatically construct filtrations of topological shapes of image texture through a technique known as persistent homology (PH); these features can then be fed into machine learning models that provide explainable outputs and can distinguish different image classes in a computationally more efficient way, when compared to other currently used methods. The aim of this review is to introduce PH and its variants and to review TDA’s recent successes in medical imaging studies.
Therapeutic potential of stem cell extracellular vesicles for ischemic stroke in preclinical rodent models: a meta-analysis
Authors: Zhao Jing , Deng Huiyin , Xun Chengfeng , Chen Chunli , Hu Zhiping , Ge Lite , Jiang Zheng 
Published: April 2023

Abstract
Background
Extracellular vesicles derived from stem cells (SC-EVs) have been proposed as a novel therapy for ischemic stroke. However, their effects remain incompletely understood. Therefore, we conducted this meta-analysis to systematically review the efficacy of SC-EVs on ischemic stroke in preclinical rodent models.

Methods
Using PubMed, EMBASE, and the Web of Science, we searched through studies published up to August 2021 that investigated the treatment effects of SC-EVs in a rodent ischemic stroke model. Infarct volume was the primary outcome. Neurological severity scores (mNSS) were the secondary outcome. The standard mean difference (SMD) and the confidence interval (CI) were calculated using a random-effects model. R and Stata 15.1 were used to conduct the meta-analysis.

Results
Twenty-one studies published from 2015 to 2021 met the inclusion criteria. We also found that SCs-EVs reduced infarct volume by an SMD of − 2.05 (95% CI − 2.70, − 1.40; P < 0.001). Meanwhile, our results revealed an overall positive effect of SCs-derived EVs on the mNSS with an SMD of − 1.42 (95% CI − 1.75, − 1.08; P < 0.001). Significant heterogeneity among studies was observed. Further stratified and sensitivity analyses did not identify the source of heterogeneity.

Conclusion
The present meta-analysis confirmed that SC-EV therapy could improve neuron function and reduce infarct volume in a preclinical rodent ischemic stroke model, providing helpful clues for human clinical trials on SC-EVs.
Homogenous subpopulation of human mesenchymal stem cells and their extracellular vesicles restore function of endometrium in an experimental rat model of Asherman syndrome
Authors: Mansouri-Kivaj Nahid , Nazari Abdoreza , Esfandiari Fereshteh , Shekari Faezeh , Ghaffari Marefat , Pakzad Mohammad , Baharvand Hossein 
Published: April 2023

Abstract
Background
Asherman syndrome (AS), or intrauterine adhesions, is a main cause of infertility in reproductive age women after endometrial injury. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) are promising candidates for therapies that repair damaged endometria. However, concerns about their efficacy are attributed to heterogeneity of the cell populations and EVs. A homogenous population of MSCs and effective EV subpopulation are needed to develop potentially promising therapeutic options in regenerative medicine.

Methods
AS model was induced by mechanical injury in adult rat uteri. Then, the animals were treated immediately with homogeneous population of human bone marrow-derived clonal MSCs (cMSCs), heterogenous parental MSCs (hMSCs), or cMSCs-derived EV subpopulations (EV20K and EV110K). The animals were sacrificed two weeks post-treatment and uterine horns were collected. The sections were taken, and hematoxylin–eosin was used to examine the repair of endometrial structure. Fibrosis was measured by Masson’s trichrome staining and α-SMA and cell proliferation by Ki67 immunostaining. The function of the uteri was explored by the result of mating trial test. Expression changes of TNFα, IL-10, VEGF, and LIF were assayed by ELISA.

Results
Histological analysis indicated fewer glands, thinner endometria, increased fibrotic areas, and decreased proliferation of epithelial and stroma of the uteri in the treated compared with intact and sham-operated animals. However, these parameters improved after transplantation of both types of cMSCs and hMSCs and/or both cryopreserved EVs subpopulations. The cMSCs demonstrated more successful implantation of the embryos in comparison with hMSCs. The tracing of the transplanted cMSCs and EVs showed that they migrated and localized in the uteri. Protein expression analysis results demonstrated downregulation of proinflammatory factor TNFα and upregulation of anti-inflammatory cytokine IL-10, and endometrial receptivity cytokines VEGF and LIF in cMSC- and EV20K-treated animals.

Conclusion
Transplantation of MSCs and EVs contributed to endometrial repair and restoration of reproductive function, likely by inhibition of excessive fibrosis and inflammation, enhancement of endometrial cell proliferation, and regulation of molecular markers related to endometrial receptivity. Compared to classical hMSCs, cMSCs were more efficient than hMSCs in restoration of reproductive function. Moreover, EV20K is more cost-effective and feasible for prevention of AS in comparison with conventional EVs (EV110K).
Removing the stumbling block of exosome applications in clinical and translational medicine: expand production and improve accuracy
Authors: Han Li , Zhao Zhirong , He Chuanshi , Li Jiami , Li Xiangyu , Lu Man 
Published: April 2023

AbstractAlthough the clinical application and transformation of exosomes are still in the exploration stage, the prospects are promising and have a profound impact on the future transformation medicine of exosomes. However, due to the limitation of production and poor targeting ability of exosomes, the extensive and rich biological functions of exosomes are restricted, and the potential of clinical transformation is limited. The current research is committed to solving the above problems and expanding the clinical application value, but it lacks an extensive, multi-angle, and comprehensive systematic summary and prospect. Therefore, we reviewed the current optimization strategies of exosomes in medical applications, including the exogenous treatment of parent cells and the improvement of extraction methods, and compared their advantages and disadvantages. Subsequently, the targeting ability was improved by carrying drugs and engineering the structure of exosomes to solve the problem of poor targeting ability in clinical transformation. In addition, we discussed other problems that may exist in the application of exosomes. Although the clinical application and transformation of exosomes are still in the exploratory stage, the prospects are promising and have a profound impact on drug delivery, clinical diagnosis and treatment, and regenerative medicine.
Label extension, single-arm, phase III study shows efficacy and safety of stempeucel® in patients with critical limb ischemia due to atherosclerotic peripheral arterial disease
Authors: Gupta Pawan Kumar , Shivashankar P. , Rajkumar M. , Mahapatra Subhendu S. , Desai Sanjay C. , Dhar Anita , Krishna Vinay , Raviraja N. S. , Bhat Samatha , Viswanathan Pachaiyappan , Kannan Suresh , Abraham Jijy , Boggarapu Hema , Manjuprasad M. S. , Udaykumar K. 
Published: April 2023

Abstract
Background
Peripheral arterial disease (PAD) of lower extremities comprises a clinical spectrum that extends from asymptomatic patients to critical limb ischemia (CLI) patients. 10% to 40% of the patients are at the risk of primary amputation. This study was planned in “no-option” patients of CLI due to atherosclerotic PAD to assess the efficacy and safety of pooled, allogeneic, adult human bone marrow-derived mesenchymal stromal cells which is already approved for marketing in India for CLI due to Buerger’s disease.

Methods
This was a single-arm, multi-centric, phase III study where mesenchymal stromal cells was injected as 2 million cells/kg body weight in the calf muscle and around the ulcer. Twenty-four patients of lower extremity CLI due to PAD with Rutherford III-5 or III-6 and ankle–brachial pressure index ≤ 0.6 and having have at least one ulcer with area between 0.5 and 10 cm2 were included in the study. These patients were evaluated over 12 months from drug administration.

Results
Over a period of 12 months, statistical significant reduction of rest pain and ulcer size along with improvement in ankle–brachial pressure index and ankle systolic was observed. The quality of life of patients improved together with increase in total walking distance and major amputation-free survival time.

Conclusion
Mesenchymal stromal cells may be a feasible option to treat “no-option” patients with atherosclerotic PAD.
Trial registration This study is registered prospectively in National Institutes of Health and Clinical Trials Registry—India (CTRI) website: CTRI/2018/06/014436. Registered 6th June 2018. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=24050&EncHid=&userName=stempeutics.