bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot Observational Study of Patient Reported Outcome Measures for Long COVID Patients in Virtual Integrative Medical Group Visits
Authors: Barnhill Jessica L , Roth Isabel J , Miller Vanessa E , Baratta John M , Chilcoat Aisha , Kavalakatt Bethany M , Tiedt Malik K , Thompson Karla L , Gardiner Paula 
Published: May 2023

Background Long COVID is a common, debilitating post-infectious illness for which effective management is unknown. Integrative Medical Group Visits (IMGV) are effective interventions for chronic conditions and could benefit Long COVID patients. More information is needed regarding existing patient reported outcome measures (PROMs) to evaluate efficacy of IMGV for Long COVID. Objective This study assessed the feasibility of specific PROMS to evaluate IMGVs for Long COVID. Findings will inform future efficacy trials. Methods The Perceived Stress Scale (PSS-10), General Anxiety Disorder two-question tool (GAD-2), Fibromyalgia Symptom Severity scale (SSS), and Measure Yourself Medical Outcome Profile (MYMOP®) were collected pre- and post-group by teleconferencing platform or telephone and compared using paired t-tests. Patients were recruited from a Long COVID specialty clinic where they participated in 2-hour - 8 weekly IMGV sessions online. Results Twenty-seven participants enrolled and completed pre-group surveys. Fourteen participants were reachable by phone post-group and completed all pre and post PROMs (78.6% female, 71.4% non-Hispanic White, mean age 49). MYMOP® primary symptomatology was fatigue, shortness of breath and “brain fog”. Symptoms decreased in interference when compared to pre-group levels (mean difference −1.3 [95% CI-2.2, −.5]). PSS scores decreased (−3.4 [95% CI -5.8, −1.1]), and GAD-2 mean difference was −1.43 (95% CI –3.12, .26). There were no changes in SSS scores of fatigue (−.21 [95% CI -.68,0.25]), waking unrefreshed (.00 [95%CI -.32, −.32]), or trouble thinking (−.21 [95% CI -.78,0.35]). Conclusion All PROMs were feasible to administer via teleconferencing platform or telephone. The PSS, GAD-2 and MYMOP® are promising PROMs to track Long COVID symptomatology among IMGV participants. The SSS, while feasible to administer, did not change compared to baseline. Larger, controlled studies are needed to determine the efficacy of virtual IMGVs to address the needs of this large and growing population.
BET inhibition targets ABC-DLBCL constitutive B-cell receptor signaling through PAX5
Authors: Oien Derek B. , Sharma Samanta , Hattersley Maureen M. , DuPont Michelle , Criscione Steven W. , Prickett Laura , Goeppert Anne U. , Drew Lisa , Yao Yi , Zhang Jingwen , Chan Ho Man 
Published: May 2023

Abstract
B-cell receptor (BCR) signaling is essential for the diffuse large B-cell lymphoma (DLBCL) subtype that originates from activated B-cells (ABCs). ABC-DLBCL cells are sensitive to Bruton tyrosine kinase intervention. However, patients with relapsed or refractory ABC-DLBCL had overall response rates from 33% to 37% for Bruton tyrosine kinase inhibitors, suggesting the evaluation of combination-based treatment for improved efficacy. We investigated the efficacy and mechanism of the bromodomain and extraterminal motif (BET) inhibitor AZD5153 combined with the Bruton tyrosine kinase inhibitor acalabrutinib in ABC-DLBCL preclinical models. AZD5153 is a bivalent BET inhibitor that simultaneously engages the 2 bromodomains of BRD4. Adding AZD5153 to acalabrutinib demonstrated combination benefits in ABC-DLBCL cell line and patient-derived xenograft models. Differential expression analyses revealed PAX5 transcriptional activity as a novel downstream effector of this drug combination. PAX5 is a transcription factor for BCR signaling genes and may be critical for perpetually active BCR signaling in ABC-DLBCL. Our analyses further indicated significant alterations in BCR, RELB/alternative NF-κB, and toll-like receptor/interferon signaling. Validation of these results mapped a positive-feedback signaling loop regulated by PAX5. We demonstrated that AZD5153 decreased PAX5 expression, whereas acalabrutinib disruption of BCR signaling inhibited PAX5 activation. Furthermore, several interferon levels were decreased by AZD5153 and acalabrutinib in tumors. Adding interferon-beta1 (IFNβ1) to cells treated with acalabrutinib partially rescued PAX5 activation. Our results demonstrate that AZD5153 enhances the efficacy of acalabrutinib through PAX5 and BCR mechanisms that are critical for ABC-DLBCL.
Prevalence of frailty and its association with clinical outcomes in myeloproliferative neoplasms: a population-based study
Authors: Bankar Aniket , Chan Wing C. , Liu Ning , Cheung Matthew , Alibhai Shabbir , Gupta Vikas 
Published: May 2023

Abstract
Clinical implications of frailty in myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are unknown. In this population-based study, all incident cases of MPN from the Ontario cancer registry between 2004 and 2019 (N = 10 336; ET = 5108; PV = 3843; MF = 1385) and their matched controls (for age, sex, residence, and income) in a 1:4 ratio were included. Baseline frailty measured using the Johns Hopkins Adjusted Clinical Groups frailty indicator and McIsaac frailty index (mFI), categorized as fit, prefrail, or frail if mFI &lt;0.10, 0.11 to 0.20, &gt;0.20), was significantly higher in ET, PV, and MF compared with matched controls (standardized mean difference of 0.27, 0.27, and 0.28). Over 23%, 20%, and 34% of patients with ET, PV, and MF were frail or prefrail despite a younger age (&lt;65 years) or minimal comorbidities. In Cox proportional regression, frailty was independently associated with worse overall survival (OS) after adjusting for age, sex, and comorbidities compared with mFI-fit patients. The hazard ratios (95% confidence interval) for OS for mFI-prefrail and mFI-frail patients were: 1.6 (1.3-1.9) and 3.6 (2.9-4.4) in ET, 1.3 (1.1-1.5) and 2.7 (2.1-3.4) in PV, and 1.2 (1.0-1.5) and 2.0 (1.5-2.7) in MF. Patients with MPN have a substantially higher prevalence of frailty compared with matched controls, which is associated with reduced OS, independent of age or comorbidities.
Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-naive unfit CLL without TP53 aberrations
Authors: Slot Matilde , Niemann Carsten Utoft , Ehlers Lars Holger , Rotbain Emelie Curovic 
Published: May 2023

Abstract
Several targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have been developed to treat patients with treatment-naive chronic lymphocytic leukemia (CLL) and have been shown to improve progression-free survival compared with chlorambucil + obinutuzumab (ClbO). However, novel targeted agents are associated with a significant cost investment. The objective of this study was to investigate the cost-effectiveness of VenO compared with ClbO and ibrutinib in treatment-naive CLL without del17p/TP53 mutation in Denmark. We used a decision-analytic modeling approach to simulate hypothetical cohorts of patients with CLL from the initiation of first-line treatment to death, including the full treatment pathway and second-line therapy. VenO, ClbO, or ibrutinib was included as first-line therapy followed by either Ven + rituximab or ibrutinib. Model outcomes were expected quality-adjusted life years (QALYs), life years (LYs), and cost per patient, which were used to calculate incremental cost-effectiveness ratios (ICERs) with a willingness to pay from €23 600 to €35 600 per QALY. Compared with ClbO, VenO was associated with a QALY gain of 1.30 (1.42 LYs) over a lifetime. The incremental cost was €12 360, resulting in an ICER of €9491 per QALY gained, indicating that VenO is cost-effective. Compared with VenO, ibrutinib was associated with a QALY gain of 0.82 (1.74 LYs) but at a substantially increased incremental cost of €247 488 over a lifetime horizon. The ICER was €302 156 per QALY, indicating that ibrutinib in first-line treatment would not be considered cost-effective in Danish health care, compared with VenO. Future analyses in fit patients with CLL are needed to determine the cost-effectiveness of VenO.
Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on Poly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers
Authors: Cai Aijia , Schneider Paul , Zheng Zeng-Ming , Beier Justus P. , Himmler Marcus , Schubert Dirk W. , Weisbach Volker , Horch Raymund E. , Arkudas Andreas 
Published: May 2023

AbstractBackgroundFor the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers.ResultsHuman Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone.ConclusionsThis is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.
The unrecognized role of fidelity in effectiveness-implementation hybrid trials: simulation study and guidance for implementation researchers
Authors: Trutschel Diana , Blatter Catherine , Simon Michael , Holle Daniela , Reuther Sven , Brunkert Thekla 
Published: May 2023

Abstract
Background
Effectiveness-implementation hybrid designs are a relatively new approach to evaluate efficacious interventions in real-world settings while concurrently gathering information on the implementation. Intervention fidelity can significantly influence the effectiveness of an intervention during implementation. However little guidance exists for applied researchers conducting effectiveness-implementation hybrid trials regarding the impact of fidelity on intervention effects and power.

Methods
We conducted a simulation study based on parameters from a clinical example study. For the simulation, we explored parallel and stepped-wedge cluster randomized trials (CRTs) and hypothetical patterns of fidelity increase during implementation: slow, linear, and fast. Based on fixed design parameters, i.e., the number of clusters (C = 6), time points (T = 7), and patients per cluster (n = 10) we used linear mixed models to estimate the intervention effect and calculated the power for different fidelity patterns. Further, we conducted a sensitivity analysis to compare outcomes based on different assumptions for the intracluster-correlation coefficient and the cluster size.

Results
Ensuring high fidelity from the beginning is central to achieve accurate intervention effect estimates in stepped-wedge and parallel CRTs. The importance of high fidelity in the earlier stages is more emphasized in stepped-wedge designs than in parallel CRTs. In contrast, if the increase of fidelity is too slow despite relatively high starting levels, the study will likely be underpowered and the intervention effect estimates will also be biased. This effect is more accentuated in parallel CRTs, here reaching 100% fidelity within the next measurement points is crucial.

Conclusions
This study discusses the importance of intervention fidelity for the study`s power and highlights different recommendations to deal with low fidelity in parallel and stepped-wedge CRTs from a design perspective. Applied researchers should consider the detrimental effect of low fidelity in their evaluation design. Overall, there are fewer options to adjust the trial design after the fact in parallel CRT as compared to stepped-wedge CRTs. Particular emphasis should be placed on the selection of contextually relevant implementation strategies.
Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer
Authors: Fanale Daniele , Brando Chiara , Corsini Lidia Rita , Cutaia Sofia , Di Donna Mariano Catello , Randazzo Ugo , Filorizzo Clarissa , Lisanti Chiara , Magrin Luigi , Gurrera Vittorio , Romano Raffaella , Dimino Alessandra , Bazan Russo Tancredi Didier , Olive Daniel , Vieni Salvatore , Pantuso Gianni , Giordano Antonio , Chiantera Vito , Russo Antonio , Bazan Viviana , Iovanna Juan Lucio 
Published: May 2023

Abstract
Background
The most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient’s clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women.

Patients and methods
Through specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan–Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models.

Results
For each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (≥ 30 months) versus short progression-free survival (PFS < 30 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that poor clinical outcome and median PFS ranging between 6 and 16 months were associated with higher baseline levels of PD-L1 (> 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 ≤ 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis ≤ 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients.

Conclusions
The identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels.
A comprehensive analysis of different types of databases reveals that CDH1 mRNA and E-cadherin protein are not downregulated in most carcinoma tissues and carcinoma cell lines
Authors: Sicairos Brihget , Alam Shorna , Du Yuchun 
Published: May 2023

Abstract
Background
The CDH1 gene codes for the epithelial-cadherin (E-cad) protein, which is embedded in the plasma membrane of epithelial cells to form adherens junctions. E-cad is known to be essential for maintaining the integrity of epithelial tissues, and the loss of E-cad has been widely considered a hallmark of metastatic cancers enabling carcinoma cells to acquire the ability to migrate and invade nearby tissues. However, this conclusion has come under scrutiny.

Methods
To assess how CDH1 and E-cad expression changes during cancer progression, we analyzed multiple large transcriptomics, proteomics, and immunohistochemistry datasets on clinical cancer samples and cancer cell lines to determine the CDH1 mRNA and E-cad protein expression profiles in tumor and normal cells.

Results
In contrast to the textbook knowledge of the loss of E-cad during tumor progression and metastasis, the levels of CDH1 mRNA and E-cad protein are either upregulated or remain unchanged in most carcinoma cells compared to normal cells. In addition, the CDH1 mRNA upregulation occurs in the early stages of tumor development and the levels remain elevated as tumors progress to later stages across most carcinoma types. Furthermore, E-cad protein levels are not downregulated in most metastatic tumor cells compared to primary tumor cells. The CDH1 mRNA and E-cad protein levels are positively correlated, and the CDH1 mRNA levels are positively correlated to cancer patient’s survival. We have discussed potential mechanisms underlying the observed expression changes in CDH1 and E-cad during tumor progression.

Conclusions
CDH1 mRNA and E-cadherin protein are not downregulated in most tumor tissues and cell lines derived from commonly occurring carcinomas. The role of E-cad in tumor progression and metastasis may have previously been oversimplified. CDH1 mRNA levels may serve as a reliable biomarker for the diagnosis of some tumors (such as colon and endometrial carcinomas) due to the marked upregulation of CDH1 mRNA in the early stages of tumor development of these carcinomas.
Clinical activity of pembrolizumab with or without chemotherapy in advanced pulmonary large-cell and large-cell neuroendocrine carcinomas: a multicenter retrospective cohort study
Authors: Song Lianxi , Zhou Fei , Xu Tian , Zeng Liang , Xia Qing , Wang Zhan , Deng Li , Li Yizhi , Qin Haoyue , Yan Huan , Huang Zhe , Mi Jinye , Xu Qinqin , Yang Nong , Zhou Caicun , Zhang Yongchang 
Published: May 2023

Abstract
Background
Immune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC).

Methods
We retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC – 37 treatment-naïve and 23 pre-treated – who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed.

Results
Of the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2–11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0–50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3–8.7) and mOS was 13.0 months (95%CI: 11.0–15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6–3.4) and mOS was 4.5 months (95% CI: 0.0–9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0–7.6) and mOS was not reached for LCNEC.

Conclusion
Our study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer.

Trial registration
NCT05023837(ESPORTA, 27/08/2021).
Factors related to postoperative vitreous hemorrhage after small-gauge vitrectomy in proliferative diabetic retinopathy patients
Authors: Zhao Meng , Chandra Aman , Xu Jun , Li Jipeng 
Published: May 2023

Abstract
Background
The role of anticoagulation or antiplatelet on post-vitrectomy vitreous hemorrhage (POVH) in patients with proliferative diabetic retinopathy (PDR) is rarely investigated in the small-gauge vitrectomy era. We investigate the relationship between the long-term use of those medications and POVH in a group of PDR patients.

Methods
A retrospective cohort study was carried out in a group of PDR patients who underwent small-gauge vitrectomy in our center. The baseline data on diabetes, diabetic complications, long-term use of anticoagulants and antiplatelet agents, ocular findings, and vitrectomy details were collected. The occurrence of POVH was recorded during at least three-month follow-up. Factors related to POVH were analyzed using logistic analysis.

Results
During a median follow-up of 16 weeks, 5% (11/220) of patients had POVH, and 75 had received antiplatelet or anticoagulation agents before the operation. Factors related to persistent POVH were the use of antiplatelet or anticoagulation agents (5.98, 1.75–20.45, p = 0.004), the presence of myocardial revascularization (130.65, 3.53-4834.50, p = 0.008), the presence of coronary artery disease (CAD) treated with medicine (56.52, 1.99–1604.06, p = 0.018), and younger age (0.86, 0.77–0.96, p = 0.012). For those receiving preoperative antiplatelet or anticoagulation agents, the probability of developing POVH was higher in the patients whose previous therapy was adjusted compared to those with continued therapy (p = 0.02 by Log-rank test).

Conclusions
We identified long-term use of anticoagulation or antiplatelet medication, the presence of CAD, and younger age as three independent factors related to POVH. In PDR patients on long-term antiplatelet or anticoagulation medications, particular attention should be given to controlling intraoperative bleeding, and follow-up for POVH should be scheduled.