bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of circulating tumor DNA analysis aimed at guiding adjuvant treatment in colorectal cancer
Authors: Henriksen Tenna V. , Demuth Christina , Frydendahl Amanda , Nors Jesper , Nesic Marijana , Rasmussen Mads H. , Larsen Ole H. , Jaensch Claudia , Løve Uffe S. , Andersen Per V. , Kolbro Thomas , Thorlacius-Ussing Ole , Monti Alessio , Kildsig Jeppe , Bondeven Peter , Schlesinger Nis H. , Iversen Lene H. , Gotschalck Kåre A. , Andersen Claus L. 
Published: February 2025

Abstract
Background: Multiple clinical trials investigate circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy (ACT) in colorectal cancer. Timely ACT initiation necessitates early ctDNA testing, but the impact of postoperative cell-free DNA (cfDNA) and ctDNA dynamics remains unclear, particularly with cost-reducing input caps employed in some assays. This study investigates ctDNA detection at day14 versus day30, comparing whole-sample analysis with capping the cfDNA input, and evaluates single and dual timepoint assessments for ACT allocation. Patients and methods: In 2019-2023, 611 stage I-III colorectal cancer patients were enrolled. Blood was collected preoperatively, and postoperatively ~day14 and ~day30. The cfDNA levels were assessed using digital PCR, and ctDNA using tumor-informed digital PCR or targeted sequencing analyzing all cfDNA from 8mL of plasma. Results: Despite elevated cfDNA in 85% of day14 samples, performance was comparable between the two timepoints (sensitivity 31% vs 32%; specificity both 98%). A 50ng cfDNA input cap reduced ctDNA detection probability, impacting 78% of day14 samples and 65% of day30 samples. At both timepoints, ctDNA detection was prognostic of recurrence (day14: HR=9.0, 95%CI 5.5-14.8; day30: HR=12.5, 95%CI 7.6-20.4). In 74% of ctDNA-positive recurrence patients, both samples had ctDNA detected. An increase in ctDNA level from day14 to day30 was associated with shorter time to recurrence (Pearson R=-0.63, P=0.003). Combining the timepoints would increase sensitivity (36%) and allow earlier ACT start in 80% of patients. Conclusion: Early ctDNA sampling is feasible and highly prognostic. Supplemental later testing may improve sensitivity while allowing early ACT initiation for most ctDNA positive patients.
Anterior Cruciate Ligament Reconstruction Return to Sport Testing Passing Rates for Healthy People: A Systematic Review
Authors: Wood Audria , Hargreaves Mathew , Manfredi John N. , Harrell Maxwell , Marks Benson Elizabeth , Rahaman Clay , Dayal Dev , Brabston Eugene W. , Evely Thomas , Casp Aaron , Momaya Amit M. 
Published: February 2025

Background: Return to sport (RTS) is a common goal after anterior cruciate ligament (ACL) reconstruction (ACLR) but carries a relatively high risk of reinjury with up to 20% to 25% of athletes experiencing graft rupture or contralateral ACL tear. While there is increased emphasis on establishing safe RTS criteria for athletes to return to previous activity levels, studies show that even healthy individuals have difficulty passing RTS testing. Purpose: To synthesize data concerning whether healthy individuals can pass ACLR RTS rehabilitation tests. Study Design: Systematic review; Level of evidence, 4. Methods: Following the established PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors conducted a systematic literature search in May 2023. Three databases were used in the search (PubMed, EMBASE, and SPORTDiscus) to retrieve all studies that conducted ACLR RTS rehabilitation tests on healthy individuals. Tests included were isometric strength, isokinetic strength, hop, and balance tests. The search was performed in duplicate, and a quality assessment of all studies was included. Results: A total of 1724 studies were retrieved, of which 32 were included, involving 1552 controls with no history of ACL injury. From the studies analyzed, 5.3% to 42.2% of healthy participants failed 6 different hop tests, 15.2% failed the Star Excursion Balance Test, 37% failed the isometric knee flexion test, 50% failed the isometric knee extension test, and 23.7% to 28.9% failed the drop vertical jump test. An asymmetry index ≥10% was found in 6 of the 18 isokinetic tests and 2 of the 14 isometric tests. Hop testing was the most common test in the included studies (56.3%), followed by balance testing (31.3%), isometric strength testing (31.3%), isokinetic strength testing (25%), and drop vertical jump (6.3%). Conclusion: Many healthy individuals fail ACLR RTS tests, with some having an inherent variation from side to side that is >10%. The passing threshold for RTS testing should be a value that is practical yet helps reduce reinjury rates.
Return to Sport in Athletes After Osteochondral Allograft Transplantation: A Systematic Review
Authors: Touhey Daniel C. , Beady Nikko D. , Tartibi Sina , Brophy Robert H. , Matava Matthew J. , Smith Matthew V. , Knapik Derrick M. 
Published: February 2025

Background: Management of symptomatic osteochondral defects of the knee remains challenging because of the limited inherent vascularity and healing potential of articular cartilage. Osteochondral allograft (OCA) transplantation has yielded satisfactory results in appropriate patients; however, the effect of OCA transplantation on athletes seeking to return to sport (RTS) remains largely unknown. Purpose: To systematically review the literature to better understand outcomes after OCA, focusing on RTS rate and timing, and the incidence of postoperative complications. Study Design: Systematic review; Level of evidence, 4. Methods: Studies included in the PubMed, EMBASE, and Cochrane Library databases from inception to August 2024 that reported on athletes participating at the recreational, high school, collegiate, and professional levels undergoing OCA transplantation for osteochondral defects in the knee were identified. Inclusion criteria included studies reporting on patients identified as athletes undergoing OCA transplantation with reported origin, lesion characteristics (size and location), RTS rate and timing, complications, reoperations, and patient-reported outcomes. Results: A total of 14 studies, consisting of 471 athletes undergoing OCA transplantation with a weighted mean follow-up of 51.1 months, were identified. The weighted mean patient age was 31.4 years (range, 15-69 years), with 61% of patients being male. Lesion origin was reported in 49% (230/471) of patients, with osteochondritis dissecans (OCD) reported in 44% (100/230). The medial femoral condyle was the most common defect location (44%; 68/153). Lesion size ranged from 1 to 13.94 cm2. Sixteen percent (75/471) of patients were classified as competitive athletes, with basketball (n = 21) being the most common sport. RTS was reported in 72% (338/468) of patients, with 84% (231/275) returning at an equal or higher level of play at a weighted mean of 11.1 months (range, 6-26 months) after OCA. Complications were reported in 12% (41/351) of patients, with graft failure accounting for 54% (22/41) of complications in 6% (22/351) of patients. Conclusion: For athletes undergoing OCA transplantation to the knee, OCD was the most commonly reported cause, with the medial femoral condyle most frequently affected. Successful RTS was reported in 72% of patients at a mean of 11.1 months, with graft failure representing the most common complication in 6%.
Lung disease classification in chest X-ray images using optimal cross stage partial bidirectional long short term memory
Authors: Babu T , Sam Kumar GV , Kartheesan L , Rajendran Surendran 
Published: February 2025

Background Lung disease is the crucial disease that affects the breathing conditions and even causes death. There are various approaches for the lung disease classification; still the inefficiency in accurate detection, computational complexity and over-fitting issues limits the performance of the model. To overcome the challenges, a deep learning model is proposed in this research. Initially, the input is acquired and is pre-processed using three various techniques like data augmentation, filtering and image re-sizing. Then, the threshold based segmentation is employed for obtaining the required region. Objective From the segmented image, various categories of lung diseases like COVID, lung Opacity, Pneumonia and normal are identified using the proposed Optimal Cross Stage Partial Bidirectional Long short term memory (OCBiNet). Methods The proposed OCBiNet is designed using Bidirectional Long short-term memory (BiNet) with Cross Stage Partial connection in its hidden state. Besides, the adjustable parameters are modified using the proposed Improved Mother Optimization (ImMO) algorithm. Results The ImMO algorithm is designed by integrating the Logistic Chaotic Mapping within the conventional Mother Optimization algorithm for enhancing the convergence rate in obtaining the global best solution. Conclusions The proposed OCBiNet is evaluated based on Accuracy, Recall, Precision, and F-Score and acquired the values of 99.11%, 98.98%, 99.18%, and 99.08% respectively.
Women with polycystic ovary syndrome is aassociated with Longer anogenital distance, a new potential biomaker for PCOS
Authors: Chen Shumin , Cui Qiulin , Wu Yue , Fan Weiwen 
Published: February 2025

Background Fetal androgen exposure plays a pivotal role in Polycystic ovary syndrome (PCOS) development and may result in elevated Anogenital distance (AGD). This meta-analysis aimed to investigate the clinical link between PCOS and AGD. Methods A literature search was performed across various databases to identify studies evaluating AGD in adults with PCOS and without, regardless of language, up to December 2024. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) scoring system. Random-effects models were utilized to determine mean differences (MDs) and 95% confidence intervals (CIs) in cases of high heterogeneity. This meta-analysis encompassed 4 studies involving a total of 837 participants. Results The pooled analysis found a noteworthy increase of the AGD-ac and AGD-af in PCOS patient compared with the control groups, with an overall MD of AGD-ac = 5.23, 95% CI (2.60, 7.85), P-value < 0.0001, I2 = 57%, and with an overall MD of AGD-af = 2.19, 95% CI (0.04, 4.35), P-value = 0.05, I2= 89%. Conclusion The meta-analysis results indicated that women diagnosed with PCOS exhibit elongated AGD. This potential association between AGD and PCOS could serve as a novel clinical marker for the diagnosis of PCOS. Fetal androgen exposure may play a role in the pathogenesis of PCOS.
Enhancing breast cancer treatment: Evaluating the efficacy of hyaluronic acid-coated tamoxifen-loaded solid lipid nanoparticles on MCF7 cells
Authors: Ghayoumipour Niloufar , Ghafouri Hossein 
Published: February 2025

Introduction Tamoxifen (TMX) shows promise in treating breast cancer, but it faces challenges such as poor solubility, instability, and incomplete release when targeting tumors. Additionally, TMX therapy’s toxicity is a critical issue in breast cancer treatment. This study aimed to assess the impact of hyaluronic acid (HA)-coated TMX-loaded solid lipid nanoparticles (HA-TMX-SLNs) on MCF7 breast cancer cells. Methods Solid lipid nanoparticles (SLNs) were prepared using hot homogenization. The HA-TMX-SLNs and TMX-SLNs were characterized and evaluated through transmission electron microscopy (TEM). Cytotoxicity was assessed using the MTT assay, and Western blot analysis was utilized to identify key factors in the cell cycle and apoptosis. Results The nanoparticles (HA-TMX-SLNs) demonstrated approximately 55% loading efficiency after 100 h. HA-TMX-SLNs exhibited lower cytotoxicity in MCF7 cells compared to other treatments. Significant decreases in expression levels of cyclin-dependent kinase (CDK) 4, Cyclin D1, CDK2, and Bcl2 were observed after treatment with HA-TMX-SLNs, along with an increase in cleaved/procaspase-7. Discussion The in vitro release study showed that HA-coated SLNs consistently released the drug into the media under controlled conditions. Furthermore, HA-TMX-SLNs exhibited cytotoxic effects, increasing apoptosis and inhibiting cancer cell proliferation. These findings suggest that HA-TMX-SLNs effectively deliver TMX to breast cancer cells.
Risk factors for bleeding in patients with thrombotic antiphospholipid syndrome during antithrombotic therapy
Authors: Gaspar Pedro , Mittal Prabal , Cohen Hannah , Isenberg David A 
Published: February 2025

Objectives We aimed to explore the prevalence and risk factors for bleeding in patients with thrombotic antiphospholipid syndrome (tAPS) on antithrombotic therapy. Methods Single-centre retrospective analysis of patients with tAPS (Sydney criteria). Bleeding events were classified according to the International Society on Thrombosis and Haemostasis as (a) major bleeding and (b) any bleeding. Risk factors for any bleeding and for major bleeding were explored using logistic regression. Results We identified 197 patients (female, 71.1%; primary APS, 65.9%; presenting with arterial thrombosis, 44.2%; median disease duration, 10 years), all of whom had been exposed to antithrombotic therapy: anticoagulation, 98.5% (90.2% warfarin), and combined antithrombotic therapy, 24.9%. Eighty patients (40.6%) experienced 167 bleedings (22.8% major bleedings). Recurrent thrombosis during treatment occurred in 26.9% of patients (58.5% arterial thrombosis), and 41.9% of patients received high-intensity anticoagulation schemes (all warfarin target INR >3). Thrombocytopenia (<150 × 109 platelets/L) affected 12.7% of patients. Secondary APS was associated with major bleeding, whereas recurrent thrombosis and high-intensity anticoagulation were associated with any bleeding. Combined antithrombotic therapy and thrombocytopenia increased the risk for any bleeding and major bleeding, with thrombocytopenia associated with both outcomes (OR = 5.58, 95% CI, 1.93–16.13; OR = 2.82, 95% CI, 1.06–7.51, respectively) after multivariate analysis. Conclusion Patients with secondary APS, those experiencing recurrent thrombosis and exposed to combined antithrombotic treatment, are particularly at risk for bleeding. Patients with thrombocytopenia warrant the most attention as it is both an independent and the strongest risk factor for bleeding that we identified.
Scutellarin Nanoparticles Inhibit Colon Cancer by Regulating Ferroptosis
Authors: Li Yuanzhi , Yue Chaochi , Liao Yingyin , Du Weiliang 
Published: February 2025

Background In our previous research, we addressed the issues of poor stability and water solubility of scutellarin by developing scutellarin nanoparticles. Our findings indicated that these nanoparticles exhibited enhanced anti-colon cancer activity compared to scutellarin alone. However, the underlying mechanisms of scutellarin’s anti-colon cancer effects require further investigation. Scutellarin is known to suppress the proliferation of different tumor cells. In this study, we explored whether scutellarin, encapsulated in nanoparticles, could suppress the proliferation of colon cancer cells by modulating ferroptosis. Purpose In this study, we explored whether scutellarin, encapsulated in nanoparticles, could suppress the proliferation of colon cancer cells by modulating ferroptosis. Methods SW480 and HCT-116 cells were divided into (a) control group, scutellarin group, and scutellarin nanoparticles group; and (b) control group, scutellarin nanoparticles group, ferrostatin-1 group, and scutellarin nanoparticles + ferrostatin-1 group. First, we determined the half-maximal inhibitory concentration of colon cancer cells by Cell Counting Kit-8 (CCK-8) assay. Then, the ferroptosis of cells in each group was detected, and the levels of oxidative stress-related factors, superoxide dismutase (SOD) and malondialdehyde (MDA), were detected by biochemical kits. Cell death was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, cell invasion was detected by Transwell assay, and reactive oxygen species (ROS) levels were detected by flow cytometry. Western blotting was used to detect ferroptosis-related glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroportin 1 (FPN1) expression levels. Results We found that in SW480 and HCT-116 cells, the IC50 of scutellarin nanoparticles cells was lower, cell apoptosis and invasion were more obvious, the oxidative stress level was also higher, Fe2+ content was increased, and the expression of GPX4, SLC7A11, and FPN1 was decreased. These results were changed after the addition of ferrostatin-1. Conclusion Scutellarin nanoparticles have a better anti-tumor effect than the same dose of scutellarin. Scutellarin nanoparticles can inhibit the proliferation, migration, and invasion of cancer cells by promoting ferroptosis, as well as cell apoptosis.
Clinical Characteristics and Outcomes of Neonates with Proven COVID-19 Infection: A Tertiary Centre Experience
Authors: Bandiya Prathik , L T Chandan Kumar , Shivanna Niranjan , Puttappanavar Ashok , Bandyopadhyay Tapas 
Published: February 2025

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects a wide range of age groups from neonates to adults. There is wide variation in the clinical presentation of the neonates. Methods All COVID-19-positive neonates as detected by reverse transcription polymerase chain reaction (RT-PCR) in the first and second wave of the COVID-19 pandemic between June 2020 and December 2021 were included in the study. The method and timing of testing were based on national guidelines. Antenatal history, neonatal demographic and baseline characteristics, clinical course, laboratory investigations and outcome data were noted. The data was analysed by standard statistical methods. Results A total of 31 neonates were included in the study. The most common presenting complaints at admission were respiratory distress (80%), lethargy (64%), refusal of feeds (54%) and weak crying (45%). Nearly 80% of neonates required oxygen at admission and 30% required mechanical ventilation. Four neonates (13%) died due to COVID-19. Elevated D-dimer values, low platelet count and elevated Serum Glutamic Pyruvic Transaminase (SGPT) levels were significant predictors for in-hospital mortality among neonates with COVID-19 infection. Conclusion Symptomatic COVID-19-positive neonates referred to a tertiary care centre have a protracted clinical course. The presence of thrombocytopenia, elevated liver enzymes and D-dimer is associated with poor clinical outcomes in these babies.
Clinical Profile of Neonates with Cardiorespiratory Failure Needing Extracorporeal Membrane Oxygenation: A Retrospective Observational Study
Authors: Panigrahi Nikita , A Venkatesh Harohalli , N Karthik Nagesh , Pejaver Rajath , NS Devananda 
Published: February 2025

Background Neonatal extracorporeal membrane oxygenation (ECMO) is a lifesaving therapeutic intervention for critically ill neonates with hypoxic respiratory or cardiac failure not responding to conventional management. Objectives To estimate the clinical profile of neonates with hypoxic respiratory failure requiring ECMO over 10 years. Methods This was a retrospective single-center observational study including all neonates requiring ECMO due to cardiorespiratory failure between 2012 and 2022 at neonatal and cardiac intensive care. Data were collected regarding clinical profile, duration of ECMO, complications, and survival rate. Results A total of 26 neonates underwent veno-arterial ECMO during the study period. The mean birth weight (BW) was 2,880 g. Post-operative congenital heart disease (CHD) ( n = 24) was the major category requiring ECMO with transposition of great vessels attributing to the most number of cases (57.6%). The mean duration of ECMO was 155.88 hours. Twenty-four neonates weighed more than 2,000 g and the survival rate was 41.6% among them, whereas the survival rate was 50% for less than 2,000 g BW neonates. The mortality was 100% and 28.5% when the duration of ECMO was more than seven days and less than seven days, respectively. The overall survival to hospital discharge was 57.7%. Conclusions Post-operative-cardiac cases were a major category in our center for undergoing ECMO with a higher survival rate noted when the ECMO was initiated within the first week of life and the duration of ECMO was less than seven days.
Pilot randomized controlled trial of extracorporeal shock wave therapy for temporomandibular joint disorders
Authors: Zhang Sheng , Jiang Yingchun , Gao Deshuai , Zhou Zheng , Zhang Qi 
Published: February 2025

Background Temporomandibular joint disorders (TMDs) are collective terms for a series of clinical diseases. However, due to the complexity of the temporomandibular joint (TMJ), TMDs are still unknown as to their pathogenesis. Objective This pilot randomized controlled trial aimed to evaluate the efficacy of extracorporeal shock wave therapy (ESWT) in conjunction with drug therapy for myogenic TMDs. Methods In accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines, we conducted a randomized controlled trial involving 60 patients diagnosed with myogenic TMDs. Patients with myogenic TMDs (Class I) were randomly divided into ESWT group and Ultrashort Wave (UW) group. The UW group was given ultrashort wave combined with drug therapy, while the ESWT group was given extracorporeal shock wave combined with drug therapy. The primary outcome was pain intensity measured by the Visual Analog Scale (VAS), and secondary outcomes included maximum mouth opening (MMO) and temporomandibular joint function indices. Results Post-treatment assessments revealed significant improvements in VAS scores and MMO in both groups ( p < 0.05). Besides, compared with the UW group, the VAS score, the degree of MMO and Friction indexes of the TMDs patients in the ESWT group were remarkably improved after treatment ( p < 0.05). Conclusion For TMDs patients, extracorporeal shock wave combined with drug therapy can more quickly and effectively relieve the pain of the patient and improve the patient's dysfunction. However, due to the limitations of a small sample size and lack of prospective registration, these findings should be interpreted with caution. Future studies with larger sample sizes and proper registration are warranted.
Barriers and Facilitators of Physical Therapy Homecare Services for Patients with Stroke in Saudi Arabia
Authors: Albishi Alaa M , Howis Al-Shaima M , Alhusaini Adel A 
Published: February 2025

Background Extensive rehabilitation following a stroke is crucial. It could be provided as home health care (HHC) and is critical in aiding patients’ recovery at home and promoting independence. Home-based rehabilitation has proven effective for patients with stroke and enhances their quality of life. Further research is necessary to support recovery at home for patients with stroke in Saudi Arabia. Objective The study aims to explore the barriers and facilitators of physical therapy homecare services for patients with stroke in Saudi Arabia. Methods A cross-sectional study using a self-administered questionnaire was distributed among 150 licensed physical therapists. Descriptive and inferential statistics were used to describe the participants’ characteristics, barriers, and facilitators. Results The physical therapists showed high confidence in stroke rehabilitation, with a mean score (16.49 + 2.37). Most of our respondents reported that patients’ refusal of service was considered the most common barrier to homecare, with a mean score of (2.78 + 0.43). The barrier scores were significantly associated with the workplace region (p = 0.04). On a positive note, (84%) identified effective communication as a facilitator, with a mean score of (2.82 + 0.43). A significant association was found among specialists working in the homecare department compared to those working at usual rehabilitation clinics (p = 0.02). Conclusions The primary challenges were patients refusing services and inadequate communication. Overcoming these barriers is crucial. Effective communication and involving a family member in the treatment program were critical factors for facilitating home care and ensuring a high level of service.