bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vocational rehabilitation technical assistance center for quality employment: Where are we now? A project review and progress summary
Authors: Bishop Malachy , Brinck Emily A. , Tansey Timothy N. , Anderson Cayte A. , Brehmer Chelsea , Castillo Stacie L. 
Published: December 2024

Background The Vocational Rehabilitation Technical Assistance Center for Quality Employment (VRTAC-QE; H264K200003) is a national technical assistance center funded, beginning in 2020, by the Rehabilitation Services Administration and intended to provide a sustainable national platform for state vocational rehabilitation agencies (SVRAs), their affiliates, persons with disabilities, employers, and policy groups to increase capacity in their ability to improve the quality and impact of vocational rehabilitation (VR) services leading to high quality competitive integrated employment (CIE). Objective This program description is designed to provide an overview of the VRTAC-QE and report activities and progress toward its goals and objectives. Methods At the conclusion of the fourth year of this five-year project, our purpose in this article is to describe the VRTAC-QE, to update the readership on our progress to-date in meeting our goals and objectives, and to share considerations for the final year of this national technical assistance center. Results In this article we describe the structure of the Center, the process of identifying and delivering training and technical assistance (TTA), and summarize the delivery of TTA to date, in terms of the project's scope and in the context of program evaluation metrics. Conclusion We conclude the article with a review of lessons learned and next steps as we enter the final year of this project.
Relationship Between Psychological Stress Scores and Urinary 5-HT Levels Over Time Under Psychological Stress
Authors: Iida Tadayuki , Ito Yasuhiro , Murayama Susumu , Yoshimaru Yuki , Tatsumi Asami 
Published: December 2024

Background: Biomarkers for psychological stress have been examined and the “gut–microbiota–brain axis” is currently attracting attention. An intervention study reported improvements in both the intestinal environment and psychological stress. However, the relationship between psychological stress scores and urinary 5-hydroxytryptamine (u-5-HT), produced by enterochromaffin cells in the intestinal tract, has not yet been investigated over time in healthy subjects under psychological stress. Therefore, the present study examined the relationship between subjective psychological stress (depression and anxiety) scores and u-5-HT levels over time in healthy women. Methods: The effects of the objective structured clinical examination (OSCE), considered to be a uniform source of psychological stress, on u-5-HT levels were assessed in 16 third-year female medical university students (21.3 ± 2.1 years old) in Japan with a normal menstrual cycle. A self-administered questionnaire consisting of Zung’s Self-rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI) was used to evaluate subjective stress 1 month, 1 week, and 1 day before and 1 week after the OSCE. Pearson’s product-momentum correlation coefficient was used to calculate the correlation coefficient between u-5-HT levels, STAI, and SDS for each examined period. Result: On the day before the OSCE, u-5-HT levels correlated with SDS and STAI (SDS: r = .524, P = .037, State-Anxiety: r = −.718, P = .002). Conclusion: A correlation was observed between subjective psychological stress scores and u-5-HT levels in healthy women under psychological stress.
Artificial intelligence-enabled non-invasive ubiquitous anemia screening: The HEMO-AI pilot study on pediatric population
Authors: Gordon Daniel , Hoffman Jason , Gamrasni Keren , Barlev Yotam , Levine Alex , Landau Tamar , Shpiegel Ronen , Lahad Avishai , Koren Ariel , Levin Carina , Naor Osnat , Lee Hannah , Liu Xin , Patel Shwetak , Chayen Gilad , Brandwein Michael 
Published: December 2024

Objective Determine whether data collected from a smartphone camera can be used to detect anemia in a pediatric population. Methods HEMO-AI (Hemoglobin Easy Measurement by Optical Artificial Intelligence), a clinical study carried out from December 2020 to February 2023, recruited patients from the Pediatric Emergency Department, Pediatric Inpatient Department and Pediatric Hematology Unit of the Haemek Medical Center, Afula, Israel. A population-based sample of 823 patients aged 6 months to 18 years who had undergone a venous blood draw for a complete blood count since being admitted to the hospital were enrolled. Patients with total leukonychia, nailbed darkening or discoloration due to medication, nail clubbing, clinically indicated jaundice, subungual hematoma, nailbed lacerations, avulsion injuries, or nail polish applied on fingernails were not eligible for study recruitment. Video and images of the patients’ hand placed in a collection chamber were collected using a smartphone camera. Results 823 samples, 531 from a 12.2 megapixel camera and 256 from a 12.2 megapixel camera, were collected. 26 samples were excluded by the study coordinator for irregularities. 97% of fingernails and 68% of skin samples were successfully identified by a post-trained machine learning model. Separate models built to detect anemia using images taken from the Pixel 3 had an average precision of 0.64 and an average recall of 0.4, whereas models built using the Pixel 6 had an average precision of 0.8 and an average recall of 0.84. Further supplementation of training data with synthetic data boosted the precision of the latter to 0.84 and the average recall to 0.87. Conclusions This study lays the groundwork for the future evolution of non-invasive, pain-free, and accessible anemia screening tools tailored specifically for pediatric patients. It identifies important sample collection parameters and design, provides critical algorithms for the pre-processing of fingernail data, and reports an initial capability to detect anemia with 87% sensitivity and 84% specificity. Trial Registration Prospectively registered on www.clinicaltrials.gov (Identifier: NCT04573244) on 15 September 2020, prior to subject recruitment.
Meta-Analysis of Learning Curve in Endoscopic Spinal Surgery: Impact on Surgical Outcomes
Authors: Álvarez de Mon-Montoliú Juan , Castro-Toral Juan , Bonome-González César , González-Murillo Manuel 
Published: December 2024

Study Design Systematic review and meta-analysis. Objective This meta-analysis aimed to evaluate the learning curve in endoscopic spinal surgery, including the time to mastery and challenges faced by novice surgeons, to improve learning and surgical outcomes. Methods Data extraction included the learning curve period and a comparison of surgeons with more experience or late period of the learning curve (late) and surgeons with less experience and in the early period of the learning curve (early) with respect to demographic, surgical, hospitalization, functional, and complication variables. Statistical analysis was performed using Review Manager 5.4.1 software. Results This meta-analysis included 16 studies (n = 1902). The average number of cases required to reach the learning curve was 32.5 ± 10.5. The uniportal technique required fewer cases (30.1 ± 10.2) than biportal technique (38.7 ± 10.3). There were no significant differences in demographic variables, operation level, or duration of symptoms between the advanced and novice surgeons. Advanced surgeons showed better outcomes in VAS leg pain at less than 6 months (SMD 0.18, 95% CI 0.01-0.34) and >6 months (SMD 0.14, 95% CI 0.02-0.27), as well as VAS back pain at > 6 months (SMD 0.16, 95% CI 0.04-0.29). The incidence of total complications was significantly higher in the novice surgeon group. The specific complications did not differ significantly between the 2 groups. Conclusions The average number of cases required to reach the learning curve was 32.5 ± 10.5. Experienced surgeons had shorter surgery and fluoroscopy times, better outcomes in leg and back pain, and a lower incidence of complications than novice surgeons.
Efficacy and Safety of Fluconazole Mucoadhesive Patches in Human Immunodeficiency Virus-Related Oral Candidiasis
Authors: Deenadayalan Srikanth , Shenoy Ashok , Kamath Ashwin , Rathnanand Mahalaxmi , Ullal Sheetal , Shenoy Nandita 
Published: December 2024

Background Opportunistic fungal infections like oral candidiasis account for a significant amount of morbidity in HIV disease and an indicator of immune suppression. Fluconazole is a broad-spectrum antifungal agent that has been extensively used in the management of oral, candidiasis. Highly efficacious fluconazole is also known to have systemic toxicity due to high drug interaction and hence the present study focuses on the formulation of bioadhesive film as a controlled release carrier for fluconazole. Materials and Methods Patients were randomised, using a computer-generated list of random numbers, into one of the three groups: patients in group A received fluconazole mucoadhesive film 20 mg (sustained release) that was to be applied at bedtime and film 10 mg (intermediate release) to be applied during the day after lunch. Results There was a significant decrease in oral discomfort, pain and clinical improvement in group A compared to group B (Fluconazole oral tablets 100 mg/day) (P = 0.005) and group C (Fluconazole Mouth rinse) (P = 0.002). The patients who received the mucoadhesive patches had a more tolerable safety profile as expected compared to the other groups. Conclusion The bioadhesive films of fluconazole were used in HIV positive patients with oral candidiasis to overcome the problems of high dose requirement of the drug and reduce associated adverse reactions in an already immunocompromised patients and improve the quality of life.
Arthroscopic Autologous Minced Cartilage Implantation of Cartilage Defects in the Knee: A 2-Year Follow-up of 62 Patients
Authors: Schneider Stefan , Ossendorff Robert , Walter Sebastian G. , Berger Moritz , Endler Christoph , Kaiser René , Ilg Ansgar , Salzmann Gian M. , Holz Johannes 
Published: December 2024

Background: Symptomatic cartilage defects of the knee joint are frequently diagnosed and can be treated with different available surgical methods. Nevertheless, there is currently no gold standard treatment for all indications. Minced cartilage implantation is increasingly coming into focus as a refined surgical technique. Purpose: To investigate the 2-year clinical and radiological outcomes of arthroscopic autologous minced cartilage repair with the standardized commercial implantation system AutoCart. Study Design: Case series; Level of evidence, 4. Methods: A total of 62 consecutive patients were included and prospectively evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Single Assessment Numeric Evaluation (SANE), and Tegner activity scale at all follow-up time points. The examination of preoperative magnetic resonance imaging (MRI) was performed using the Area Measurement and Depth and Underlying Structures (AMADEUS) score, and the examination of MRI at 24 months was performed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score. Results: There were 34 male and 28 female patients (mean age, 38.79 ± 10.78 years) with symptomatic cartilage lesions with a mean defect size of 2.53 ± 1.24 cm2. Lesions were predominantly International Cartilage Repair Society grade 3 located in the region of the femoral condyles. Concomitant surgery was performed in 40.3% of patients. The total KOOS score significantly improved from 62.4 ± 13.1 at baseline to 74.4 ± 15.9 at 24 months ( P < .001). The secondary outcome measures of the VAS, WOMAC, and SANE showed a similar pattern, with score improvements in the follow-up period compared to baseline. The mean AMADEUS score was 64.75 ± 13.87, while the mean MOCART 2.0 score was 62.88 ± 9.86, among 20 available patients. The revision surgery rate was 8.1% mainly because of hypertrophy (6.5%). Conclusion: Among this cohort of patients, minced cartilage implantation demonstrated satisfying 2-year outcomes with increased patient-reported outcome measure scores from 3 to 24 months postoperatively. Regenerated tissue quality on MRI was comparable to that using other cartilage repair methods and showed no associations with patient characteristics or patient-reported outcome measures. Larger cohorts, longer postoperative intervals, and comparable trials are needed to further evaluate the role of this technique in treating cartilage defects.
Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma
Authors: Zeng Longhui , Zhang Xinyan , Xiong Yiwei , Hajicek Nicole , Sondek John , Su Xiaolei 
Published: December 2024

The phospholipase PLCγ1 is essential for T cell activation. It is frequently mutated in Adult T-cell leukemia/lymphoma (ATLL), Peripheral T-cell lymphomas (PTCL), and Cutaneous T-cell lymphoma (CTCL). However, the molecular mechanisms of PLCγ1 mutation in pathogenesis of these T cell malignancies remains unclear. Liquid-liquid phase separation (LLPS) is an emerging principle in organizing cellular signaling. The dysregulation of LLPS derived by aberrant protein aggregation is progressively implicated as pathological mechanism in tumorigenesis. We previously reported that PLCγ1 structurally promotes LLPS of linker for activation of T cells (LAT) to form condensates in physiological TCR signaling. These lead us to hypothesize that leukemia associated PLCγ1 mutations enhanced TCR signaling and T cell growth by promoting abnormal LLPS.
Three frequent and persistent PLCγ1 mutations (R48W, S345F, and D1165H) were chosen in this study. The mutated PLCγ1 recombinant proteins significantly boosted membrane associated LAT condensation compared with wild type (WT) at physiological concentration in a membrane-based biochemical reconstitution system. Increased condensation of LAT was confirmed in live T cells through total internal reflection fluorescence (TIRF) microcopy. Consequently, the downstream signaling including calcium influx and ERK phosphorylation were enhanced in T cell cancer lines harboring PLCγ1 mutations. PLCγ1 mutations also significantly induced the secretion of cytokines and chemokines such as IL-2 and CXCL10. Ectopically expression of PLCγ1 mutants in human primary T cells promotes T cell proliferation, CD69 expression, and effector memory T cell development. Together, these results suggested that leukemia-associated PLCγ1 mutations drive abnormal LLPS to boost TCR signaling and promote T cell proliferation.
We also determined if PLCγ1 mutations render any drug resistance by testing a few T cell lymphoma drugs in clinical use. The T cell lymphoma cell line Hut78 expressing PLCγ1 mutations showed resistance to histone deacetylase (HDAC) inhibitors. Moreover, PLCγ1 mutations reduced apoptosis under HDAC inhibition, with a company of enhanced Bcl-2 expression. The Human protein kinase phosphorylation array assay was performed to reveal the mechanism underlying drug resistance. We found that inhibiting MAPK could reverse the HDAC inhibitor resistance at non-cytotoxicity concentrations. These results demonstrated that PLCγ1-MAPK signaling axis confers the HDAC inhibitor resistance.
In summary, leukemia-associated PLCγ1 mutations facilitate abnormal LLPS formation to enhance the T cell receptor signaling. Gain-of-function of PLCγ1 mutations cause drug resistance to HDAC inhibitors, which can be rehabilitated by inhibiting the MAPK pathway. Our work reveals molecular mechanisms underlying T cell lymphomagenesis and provides solutions to patients suffering from drug resistance.
The Association between Serum Ferritin and Survival Outcome in AML Patients: A Meta-Analysis
Authors: Tanariyakul Manasawee , Wannaphut Chalothorn , Fangsaard Panisara , Kanitthamniyom Chanakarn , Wattanachayakul Phuuwadith , Saowapa Sakditad 
Published: December 2024

Background
Serum ferritin (SF), a test that measures body's iron stores and inflammation, has been established as a worthwhile prognostic impact indicator for myelodysplastic syndromes, including acute myeloid leukemia (AML). Thus, we sought to conduct a meta-analysis on the significance of SF in the prognosis of AML patients receiving treatment.
Methods
In May 2024, a PRISMA-compliant search for relevant studies until May 2024 was conducted. This search was based on PubMed, Web of Science, Scopus, and the Cochrane Library. Pooled Hazard Ratios of survival rates in AML patients based on their SF levels and 95% CIs were utilized as effect sizes. A Review Manager software was utilized for all data analyses.
Results
Five studies with an overall sample of 1237 clinically diagnosed AML patients, De novo or secondary AML, were pooled. Pooled results from the studies showed a poor prognostic association in terms of overall survival (OS) with high SF (&gt; 800 µg/L) level, with a pooled Hazard Ratio of (HR: 2.01; 95% CI: 1.45 - 2.77). Moreover, four out of five studies compared survival rates for Progression Free Survival, Disease Free Survival (DFS), Recurrence Free Survival (RFS), and Event-Free Survival (EFS). Despite the significant heterogeneity, a pooled HR still showed a poorer prognostic association between high SF and AML (HR: 1.88; 95% CI: 1.29 - 2.75).
Conclusion
Elevated SF levels have been associated with adverse effects on the prognosis of AML patients.
Ferritin Level As a Prognostic Marker for Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis
Authors: Saowapa Sakditad , Polpichai Natchaya , Garcia Pleitez Hector , Bernal Diego Olavarria , Tanariyakul Manasawee , Wannaphut Chalothorn , McCullough Maireigh , Moreira Mariana , Kanitthamniyom Chanakarn , Siladech Pharit , Tijani Lukman 
Published: December 2024

Background
Elevated serum ferritin (SF) has been associated with poor prognosis in several malignancies. However, little is known about the relationship between SF and survival outcomes of patients with non-Hodgin lymphoma (NHL). Therefore, the present meta-analysis has investigated the prognostic value of SF in NHL patients.
Methods
A systematic search for literature evaluating the prognostic effect of SF on NHL or its subtypes was conducted on PubMed, MEDLINE, Web of Science, and Google Scholar databases. The search was limited to records authored in English and published from inception until June 2024. A random-effects model was used in pooling hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS), of which the overall estimates were presented alongside their corresponding 95% confidence interval (CI). Moreover, data presented using Kaplan Meier (KM) curves, the survival probabilities, and time intervals were retrieved using WebPlotDigitizer, after which individual patient data (IPD) was reconstructed using IPDfromKM Shiny App.
Results
Ten studies with 1384 NHL patients were eligible for inclusion. The pooled data from these studies showed that high pretreatment SF was significantly associated with poor OS (HR: 2.68; 95% CI: 2.08 - 3.47, p&lt;0.00001). Similarly, data pooled from six included studies showed a significant correlation between elevated SF levels and poor PFS (HR: 2.25; 95% CI: 1.79 - 2.83, p&lt;0.00001). Furthermore, the subgroup analyses showed that elevated SF was a prognostic marker for poor OS and PFS regardless of the cut-off level and NHL subtypes. However, one study carried out in Africa did not find any considerable relationship between SF and OS 2.38 (1.01 - 5.60, p = 0.00001).
Conclusion
Overall, SF might help predict the survival outcomes of patients diagnosed with different NHL subtypes. However, further research in large-scale prospective studies is needed to validate this finding.
A Hepatic Impairment Index for Mortality Prediction in NK/T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis
Authors: Yehua Yu , Shi Jun 
Published: December 2024

Background: Hepatic impairment is a severe complication in natural killer/T cell lymphoma with hemophagocytic lymphohistiocytosis (NK/T-HLH). Abnormal levels of liver enzymes, bilirubin or albumin serve as features of hepatic impairment，but its critical indicators correlated with prognosis in NK/T-HLH remains unclear.
Patients and Methods: We conducted a retrospective study including 47 NK/T patients with and without HLH. Logistic regression and receiver-operating curve analyses were used to identify the most useful prognostic parameters of hepatic and to optimize laboratory cutoff values. Correlated factors of hepatic compromise was analyzed with Pearson's r-test.
Results: The incidence of patients experiencing hepatic impairment was 100% among 17 NK/T with HLH (NK/T-HLH), notably higher than the 50% incidence of 30 without HLH (NK/T-NHLH). Among hepatic features, gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and direct bilirubin (DBIL) can serve as important predictive markers for mortality in NK/T patients. Integrating GGT, AST, and DBIL into a novel index that we termed the GSD index, which achieved an improved mortality predictive. The respective cut-off values for these three parameters were determined using ROC curves at GGT 181.8 U/L, AST 98.5 U/L, and DBIL 6.4 μmol/L. Moreover, patients with NK/T-HLH who fulfilled the GSD index criteria exhibited a significantly shorter median survival time compared to those who did not. Interferon-gamma (IFN-γ) is an important cytokine produced by immune cells that is often elevated in HLH patients. Our analysis revealed a significant and positive linear correlation between IFN-γ levels and the elevation of GGT, ALT, AST, and DBIL. Finally, we report two successful cases of NK/T-HLH patients with severe hepatic failure using a combination treatment of chemotherapy and emapalumab, a fully human anti-IFN-γ monoclonal antibody approved for treatment of patients with primary HLH.
Conclusion: The GSD index is critical for predicting poor outcomes in NK/T-HLH patients with hepatic impairment. Emapalumab combined with chemotherapy may be an effective treatment for those with severe liver damage.
Inhibition of PKM2 Promotes Chemosensitivity of DOX in ABC-DLBCL Via Imbalance of Gsh/ROS and Inhibition of the NF-ΚB Pathway
Authors: Yang Yutian , Zhan Minglang , Hanzhen Zhang , Wei Xiaolei , Wei Yongqiang , Feng Ru 
Published: December 2024

Some patients with activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) remain resistant to the CHOP (cyclophosphamide, vincristine, doxorubicin [DOX], and prednisone) and rituximab (R)-CHOP treatment regimens. DOX induces reactive oxygen species (ROS) accumulation in ABC-DLBCL. Pyruvate kinase 2 (PKM2) is a crucial enzyme in glycolysis and plays metabolic and non-metabolic functions in tumor development. However, the role of PKM2 in modulating DOX sensitivity in ABC-DLBCL is unclear. In this study, PKM gene was highly expressed in common databases, and high PKM expression predicts poor prognosis. Inhibiting PKM2 increased DOX chemosensitivity and assisted DOX to induce cell apoptosis and cell cycle arrest. In the metabolic function of PKM2, inhibiting and knocking down PKM2 assisted DOX to inhibit glycolysis, disrupted the glutathione (GSH)/ROS balance, and activated oxidative stress-related pathways. Supplementation with GSH-MEE ameliorated ROS accumulation and apoptosis caused by DOX/PKM2i treatment. In the non-metabolic function of PKM2, inhibiting PKM2 caused DOX-induced NF-κB signaling pathway suppression. The histone acetyltransferases and deacetylases inhibitor chidamide functioned concurrently with DOX to inhibit cell viability and decreased PKM2 expression. In conclusion, this study revealed that enhanced DOX chemosensitivity can be achieved by inhibiting the metabolic and non-metabolic functions of PKM2 and partly elucidated the anti-tumor mechanism of chidamide.
Key Words:
DLBCL; PKM2; DOX; glycolysis; GSH/ROS; NF-κB; chidamide