bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic role of Twist-1 protein in hydatidiform molar pregnancies and investigation of its potential diagnostic utility in complete moles
Authors: Jahanbin Behnaz , Sarmadi Soheila , Ghasemi Dorsa , Nili Fatemeh , Moradi Jafar-Ali , Ghasemi Soha 
Published: March 2023

Abstract
Background
Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary.

Methods
In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score.

Results
Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p < 0.001). Moderate to strong staining intensity in more than 50% of villous stromal cells, can differentiate CM and PM with 89.5% sensitivity and 75% specificity. In syncytiotrophoblasts of CM, Twist-1 expression was significantly lower than PM (p < 0.001). Negative or weak staining intensity in less than 10% of syncytiotrophoblasts, can distinguish CM and PM with 82.9% sensitivity and 60% specificity.

Conclusion
A higher expression of Twist-1 in villous stromal cells of hydatidiform moles is a sensitive and specific marker for the diagnosis of CMs. An elevated expression of this marker in villous stromal cells suggests another pathogenic mechanism for more aggressiveness of CMs in addition to the characteristics of trophoblast cells. The opposite result was obtained in the expression of Twist-1 in the syncytiotrophoblasts, compatible with defects in the process of formation of these supportive cells in CMs.
Hospital mortality of blunt abdominal aortic injury (BAAI): a systematic review and meta-analysis
Authors: Li Mingxuan , Yan Yu , Wang Chaonan , Tu Haixia 
Published: March 2023

Abstract
Background
Studies on the mortality of blunt abdominal aortic injury (BAAI) are rare and have yielded inconsistent results. In the present study, we aimed to quantitatively analyse the retrieved data to more accurately determine the hospital mortality of BAAI.

Methods
The Excerpta Medica Database, PubMed, Web of Science and Cochrane Library databases were searched to identify relevant publications without date restrictions. The overall hospital mortality (OHM) of BAAI patients was set as the primary outcome measure. English publications with data that met the selection criteria were included. The quality of all included studies was assessed by the Joanna Briggs Institute checklist and the American Agency for Health Care Quality and Research’s cross-sectional study quality evaluation items. After data extraction, a meta-analysis of the Freeman–Tukey double arcsine transformation of data was performed using the Metaprop command in Stata 16 software. Heterogeneity was assessed and reported as a percentage using the I2 index value and as a P value using the Cochrane Q test. Various methods were used to determine the sources of heterogeneity and to analyse the sensitivity of the computation model.

Results
Of the 2147 references screened, 5 studies that involved 1593 patients met the selection criteria and were included. There were no low-quality references after assessment. One study that only included 16 juvenile BAAI patients was excluded from the meta-analysis of the primary outcome measure due to high heterogeneity. Due to the low heterogeneity (I2 = 47.6%, P = 0.126 for Q test) that was observed after using the random effects model, the fixed model was subsequently used to pool the effect sizes of the remaining four studies, thus yielding an OHM of 28.8% [95% confidence interval (CI) 26.5–31.1%]. The stability of the model was verified by sensitivity analysis, and Egger’s test (P = 0.339) indicated a low level of publication bias. In addition, we also performed meta-analyses and obtained a pooled hospital mortality of operation (13.5%, 95% CI 8.0–20.0%), a pooled hospital mortality of non-operation (28.4%, 95% CI 25.9–31.0%), and a pooled rate of aortic rupture (12.2%, 95% CI 7.0–18.5%) of BAAI.

Conclusions
The present study indicated that BAAI has an OHM of 28.8%, indicating that this disease deserves more attention and research.
Rates of discontinuation and non-publication of upper and lower extremity fracture clinical trials
Authors: Shepard Samuel , Anderson J. Michael , Heigle Benjamin , Thompson Jay C. , Detweiler Byron , Hartwell Micah , Vassar Matt 
Published: March 2023

Abstract
Purpose
To our knowledge, no study has quantified the rate of discontinuation and nonpublication of randomized controlled trials (RCTs) regarding upper and lower extremity fractures.

Methods
We searched ClinicalTrials.gov on September 9th, 2020, for phase 3 and 4 RCTs pertaining to upper and lower extremity fractures. Trial completion status was determined using records available on ClinicalTrials.gov. Publication status was determined using records on ClinicalTrials.gov and by searching PubMed (MEDLINE), Embase, and Google Scholar. We queried corresponding authors on trial status if a peer-reviewed publication was not identified.

Results
Our final analysis included 142 RCTs, of which 57 (40.1%) were discontinued and 71 (50%) were unpublished. Thirty-six (of 57, 63.2%) discontinued trials failed to provide a reason for discontinuation, the most commonly identified reason for discontinuation was due to inadequate recruitment (13/21, 61.9%). Completed trials were more likely to reach publication (59/85; 69.4%; X2 = 32.92; P ≤ 0.001) than discontinued trials. Trials with more than 80 participants were less likely not to reach publication (AOR: 0.12; 95% CI 0.15–0.66).

Conclusion
Our analysis of 142 upper and lower extremity fracture RCTs demonstrated one-half failed to reach publication and two-fifths were discontinued prior to trial completion. These findings indicate the need for increased guidance in developing, completing, and publishing RCTs in upper and lower extremity fractures. Discontinuation and nonpublication of orthopaedic RCTs hinder the public’s access to collected data and negate the valued contribution from study participants. Discontinuation and non-publication of clinical trials may subject participants to potentially harmful interventions, limit the advancement of clinical research, and contribute to research waste.
Level of Evidence: III.
Effects of eight-week high-intensity interval training on some metabolic, hormonal and cardiovascular indices in women with PCOS: a randomized controlled trail
Authors: Mohammadi Somayeh , Monazzami Amirabbas , alavimilani Solmaz 
Published: March 2023

Abstract
Background
Studies have revealed that high-intensity interval training (HIIT) has beneficial effect on hormonal, cardiovascular indices in women with polycystic ovary syndrome (PCOS). There, however, is still no comprehensive data on the type, intensity and duration of training for these women.

Objective
The current study aimed to investigate the effects of high-intensity interval training (HIIT) on metabolic, hormonal and cardiovascular indices in women with PCOS compared to a control group.

Methods
In a randomized controlled study, 28 patients (age: 23.8 ± 5.3 years, weight: 82.4 ± 9.7 kg, BMI: 30.33 ± 3.99 kg/m2) were divided into two groups including HIIT (n = 14) and the control (n = 14). The training protocol was performed with 100–110 maximum aerobic velocity (MAV), 4–6 sets, 4 laps, 3 sessions per week for eight weeks. Anthropometric indices, aerobic performance, insulin resistance and sensitivity, lipid profiles, testosterone, cortisol and hs-CRP were evaluated.

Results
The HIIT intervention decreased BMI, waist to hip ratio (WHR), visceral fat, insulin, insulin resistance, low density lipoprotein (LDL), atherogenic index, cholesterol and cortisol (P < 0.05). All variables remained unchanged in the control group (P > 0.05). Except for VAI, FBG, HDL, TG and AIP, the rest of the variables in the training and control groups show a significant difference (P < 0.05).

Conclusion
The results of the present study indicate that eight weeks of HIIT has beneficial effects on anthropometric, insulin sensitivity, fat profile, and inflammatory and cardiovascular indices in PCOS patients. It seems that the intensity of HIIT (100–110 MAV) is a determining factor in creating optimal adaptations in PCOS patients.
Trail registration: IRCT20130812014333N143. Registration date: 22/03/2020. URL: https://en.irct.ir/trial/46295.
Distinguishable DNA methylation defines a cardiac-specific epigenetic clock
Authors: Mongelli A. , Panunzi S. , Nesta M. , Gottardi Zamperla M. , Atlante S. , Barbi V. , Mongiardini V. , Ferraro F. , De Martino S. , Cis L. , Re A. , Maltese S. , Bachetti T. , La Rovere M. T. , Martelli F. , Pesce M. , Nanni S. , Massetti M. , Pontecorvi A. , Farsetti A. , Gaetano C. 
Published: March 2023

Abstract
Background
The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age.

Results
Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume.

Conclusion
This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.
A clinical–radiomics model based on noncontrast computed tomography to predict hemorrhagic transformation after stroke by machine learning: a multicenter study
Authors: Ren Huanhuan , Song Haojie , Wang Jingjie , Xiong Hua , Long Bangyuan , Gong Meilin , Liu Jiayang , He Zhanping , Liu Li , Jiang Xili , Li Lifeng , Li Hanjian , Cui Shaoguo , Li Yongmei 
Published: March 2023

Abstract
Objective
To build a clinical–radiomics model based on noncontrast computed tomography images to identify the risk of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT).

Materials and methods
A total of 517 consecutive patients with AIS were screened for inclusion. Datasets from six hospitals were randomly divided into a training cohort and an internal cohort with an 8:2 ratio. The dataset of the seventh hospital was used for an independent external verification. The best dimensionality reduction method to choose features and the best machine learning (ML) algorithm to develop a model were selected. Then, the clinical, radiomics and clinical–radiomics models were developed. Finally, the performance of the models was measured using the area under the receiver operating characteristic curve (AUC).

Results
Of 517 from seven hospitals, 249 (48%) had HT. The best method for choosing features was recursive feature elimination, and the best ML algorithm to build models was extreme gradient boosting. In distinguishing patients with HT, the AUC of the clinical model was 0.898 (95% CI 0.873–0.921) in the internal validation cohort, and 0.911 (95% CI 0.891–0.928) in the external validation cohort; the AUC of radiomics model was 0.922 (95% CI 0.896–0.941) and 0.883 (95% CI 0.851–0.902), while the AUC of clinical–radiomics model was 0.950 (95% CI 0.925–0.967) and 0.942 (95% CI 0.927–0.958) respectively.

Conclusion
The proposed clinical–radiomics model is a dependable approach that could provide risk assessment of HT for patients who receive IVT after stroke.
Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration
Authors: Lu Ye , Mai Zizhao , Cui Li , Zhao Xinyuan 
Published: March 2023

AbstractMesenchymal stem cell-based therapy has become an effective therapeutic approach for bone regeneration. However, there are still limitations in successful clinical translation. Recently, the secretome of mesenchymal stem cells, especially exosome, plays a critical role in promoting bone repair and regeneration. Exosomes are nanosized, lipid bilayer-enclosed structures carrying proteins, lipids, RNAs, metabolites, growth factors, and cytokines and have attracted great attention for their potential application in bone regenerative medicine. In addition, preconditioning of parental cells and exosome engineering can enhance the regenerative potential of exosomes for treating bone defects. Moreover, with recent advancements in various biomaterials to enhance the therapeutic functions of exosomes, biomaterial-assisted exosomes have become a promising strategy for bone regeneration. This review discusses different insights regarding the roles of exosomes in bone regeneration and summarizes the applications of engineering exosomes and biomaterial-assisted exosomes as safe and versatile bone regeneration agent delivery platforms. The current hurdles of transitioning exosomes from bench to bedside are also discussed.
TMED3 promotes the development of malignant melanoma by targeting CDCA8 and regulating PI3K/Akt pathway
Authors: Guo Xianling , Yin Xiaolan , Xu Yu , Li Liang , Yuan Min , Zhao Huaxin , Jiang Yuxiong , Shi Xiujuan , Bi Hongda , Liu Yeqiang , Chen Yong , Xu Qing 
Published: March 2023

Abstract
Background
Transmembrane emp24 domain containing (TMED) proteins are known to play pivotal roles in normal development, but have been reported to be implicated in pancreatic disease, immune system disorders, and cancers. As far as TMED3 is concerned, its roles in cancers are controversial. However, evidence describing TMED3 in the context of malignant melanoma (MM) is scarce.

Results
In this study, we characterized the functional significance of TMED3 in MM and identified TMED3 as a tumor-promoting factor in MM development. Depletion of TMED3 arrested the development of MM in vitro and in vivo. Mechanistically, we found that TMED3 could interact with Cell division cycle associated 8 (CDCA8). Knocking down CDCA8 suppressed cell events associated with MM development. On the contrary, elevating CDCA8 augmented cell viability and motility and even reversed the inhibitory effects of TMED3 knockdown on MM development. On the other hand, we found that the levels of P-Akt and P-PI3K were decreased in response to TMED3 downregulation, which was partially abolished following SC79 treatment. Thus, our suspicion was that TMED3 exacerbates MM progression via PI3K/Akt pathway. More notably, previously decreased P-Akt and P-PI3K in TMED3-depleted cells were rescued after overexpressing CDCA8. Also, previously impaired cell events due to CDCA8 depletion were ameliorated after SC79 addition, implying that TMED3 regulates PI3K-AKT pathway via CDCA8, thereby promoting MM development.

Conclusions
Collectively, this study established the link between TMED3 and MM, and provides a potential therapeutic intervention for patients with MM harboring abundant TMED3.
“Sign Me Up”: a qualitative study of video observed therapy (VOT) for patients receiving expedited methadone take-homes during the COVID-19 pandemic
Authors: Darnton James B. , Bhatraju Elenore P. , Beima-Sofie Kristin , Michaels Alyssa , Hallgren Kevin A. , Soth Sean , Grekin Paul , Woolworth Steve , Tsui Judith I. 
Published: March 2023

Abstract
Background
Federal and state regulations require frequent direct observation of methadone ingestion at an Opioid Treatment Program (OTP)—a requirement that creates barriers to patient access. Video observed therapy (VOT) may help to address public health and safety concerns of providing take-home medications while simultaneously reducing barriers to treatment access and long-term retention. Evaluating user experiences with VOT is important for understanding the acceptability of this strategy.

Methods
We conducted a qualitative evaluation of a clinical pilot program of VOT via smartphone that was rapidly implemented between April and August 2020 during the COVID-19 pandemic within three opioid treatment programs. In the program, selected patients submitted video recordings of themselves ingesting methadone take-home doses, which were asynchronously reviewed by their counselor. We recruited participating patients and counselors for semi-structured, individual interviews to explore their VOT experiences after program completion. Interviews were audio recorded and transcribed. Transcripts were analyzed using thematic analysis to identify key factors influencing acceptability and the effect of VOT on the treatment experience.

Results
We interviewed 12 of the 60 patients who participated in the clinical pilot and 3 of the 5 counselors. Overall, patients were enthusiastic about VOT, noting multiple benefits over traditional treatment experiences, including avoiding frequent travel to the clinic. Some noted how this allowed them to better meet recovery goals by avoiding a potentially triggering environment. Most appreciated having increased time to devote to other life priorities, including maintaining consistent employment. Participants described how VOT increased their autonomy, allowed them to keep treatment private, and normalized treatment to align with other medications that do not require in-person dosing. Participants did not describe major usability issues or privacy concerns with submitting videos. Some participants reported feeling disconnected from counselors while others felt more connected. Counselors felt some discomfort in their new role confirming medication ingestion but saw VOT as a useful tool for select patients.

Conclusions
VOT may be an acceptable tool to achieve equipoise between lowering barriers to treatment with methadone and protecting the health and safety of patients and their communities.
Myeloid-derived suppressor cells: key immunosuppressive regulators and therapeutic targets in hematological malignancies
Authors: Wang Shifen , Zhao Xingyun , Wu Siwen , Cui Dawei , Xu Zhenshu 
Published: March 2023

AbstractThe immunosuppressive tumor microenvironment (TME) supports the development of tumors and limits tumor immunotherapy, including hematological malignancies. Hematological malignancies remain a major public health issue with high morbidity and mortality worldwide. As an important component of immunosuppressive regulators, the phenotypic characteristics and prognostic value of myeloid-derived suppressor cells (MDSCs) have received much attention. A variety of MDSC-targeting therapeutic approaches have produced encouraging outcomes. However, the use of various MDSC-targeted treatment strategies in hematologic malignancies is still difficult due to the heterogeneity of hematologic malignancies and the complexity of the immune system. In this review, we summarize the biological functions of MDSCs and further provide a summary of the phenotypes and suppressive mechanisms of MDSC populations expanded in various types of hematological malignancy contexts. Moreover, we discussed the clinical correlation between MDSCs and the diagnosis of malignant hematological disease, as well as the drugs targeting MDSCs, and focused on summarizing the therapeutic strategies in combination with other immunotherapies, such as various immune checkpoint inhibitors (ICIs), that are under active investigation. We highlight the new direction of targeting MDSCs to improve the therapeutic efficacy of tumors.
Measures of success: characterizing teaching and teaching change with segmented and holistic observation data
Authors: Weston Timothy J. , Laursen Sandra L. , Hayward Charles N. 
Published: March 2023

AbstractBackgroundNumerous studies show that active and engaging classrooms help students learn and persist in college, but adoption of new teaching practices has been slow. Professional development programs encourage instructors to implement new teaching methods and change the status quo in STEM undergraduate teaching, and structured observations of classrooms can be used in multiple ways to describe and assess this instruction. We addressed the challenge of measuring instructional change with observational protocols, data that often do not lend themselves easily to statistical comparisons. Challenges using observational data in comparative research designs include lack of descriptive utility for holistic measures and problems related to construct representation, non-normal distributions and Type-I error inflation for segmented measures.ResultsWe grouped 790 mathematics classes from 74 instructors using Latent Profile Analysis (a statistical clustering technique) and found four reliable categories of classes. Based on this grouping we proposed a simple proportional measure we called Proportion Non-Didactic Lecture (PND). The measure aggregated the proportions of interactive to lecture classes for each instructor. We tested the PND and a measure derived from the Reformed Teaching Observation Protocol (RTOP) with data from a professional development study. The PND worked in simple hypothesis tests but lacked some statistical power due to possible ceiling effects. However, the PND provided effective descriptions of changes in instructional approaches from pre to post. In tandem with examining the proportional measure, we also examined the RTOP-Sum, an existing outcome measure used in comparison studies. The measure is based on the aggregated items in a holistic observational protocol. As an aggregate measure we found it to be highly reliable, correlated highly with the PND, and had more statistical power than the PND. However, the RTOP measure did not provide the thick descriptions of teaching afforded by the PND.ConclusionsFindings suggest that useful dependent measures can be derived from both segmented and holistic observational measures. Both have strengths and weaknesses: measures from segmented data are best at describing changes in teaching, while measures derived from the RTOP have more statistical power. Determining the validity of these measures is important for future use of observational data in comparative studies.