bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriateness of the EQ-5D-5L in capturing health-related quality of life in individuals with transfusion-dependent β-thalassemia: a mixed methods study
Authors: Boateng-Kuffour Adriana , Skrobanski Hanna , Drahos Jennifer , Kohli Puja , Forster Katie , Acaster Sarah , Pakbaz Zahra , Li Nanxin , Williams Kate
Published: July 2024

Background

Individuals with transfusion-dependent β-thalassemia (TDT) experience symptoms and functional impacts that reduce their health-related quality of life. However, EQ-5D-derived health utility index scores in TDT often indicate good HRQoL, suggesting the EQ-5D may not adequately capture the impact of TDT. This study explored the disease and treatment burden of TDT and examined the appropriateness of the EQ-5D-5L descriptive system (DS) in measuring HRQoL in TDT.

Methods

Adults with TDT in the United Kingdom, United States, and France completed a background questionnaire and EQ-5D-5L DS, followed by 60-minute semi-structured interviews on symptoms and HRQoL impacts of TDT (concept elicitation) and appropriateness of EQ-5D-5L DS (cognitive debrief). Transcribed interviews were analyzed using thematic and content analyses. The relationship between TDT symptoms and impacts were summarized in a conceptual model. EQ-5D-5L DS was mapped to concepts identified in the qualitative data to assess its capture of HRQoL concepts. Participants’ EQ-5D-5L DS scores were compared to their qualitative descriptions for each dimension to assess their concordance.

Results

Thirty participants in the United States (n = 14 [46.7%]), United Kingdom. (n = 12 [40.0%]), and France (n = 4 [13.3%]) completed the study (73.3% female; mean age = 28.4 years [standard deviation (SD) = 5.1]; mean annual red blood cell transfusion [RBCT] frequency = 18.4 [SD = 7.6]). Participants reported TDT symptoms and impacts on HRQoL, all fluctuating across the RBCT cycle. EQ-5D-5L DS did not fully capture 11 of 16 (68.8%) HRQoL concepts reported. Most participants (n = 20/27 [74.1%]) reported that EQ-5D-5L DS did not capture important aspects of living with TDT, and 42.9% (n = 12/28) reported negative/neutral overall impressions of EQ-5D-5L DS. The highest degree of discordance between participants’ qualitative data and EQ-5D-5L DS dimension scores was observed with mobility (42.3%) and self-care (34.6%), where the qualitative descriptions relating to these dimensions were worse than their quantitative scores.

Conclusion

Current findings suggest that EQ-5D-5L DS lacks content validity and the derived health utility index score may not fully represent the burden of disease in TDT.
Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer
Authors: Shen Yicheng , Shan Jiebo
Published: July 2024

Objective

The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables.

Methods

Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model.

Results

A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36–4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17–3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT.

Conclusion

Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.
Efficacy of Interceptor G2, Royal Guard and PermaNet 3.0 against pyrethroid-resistant Anopheles gambiae s.l. from Za-Kpota, southern Benin: an experimental hut trial
Authors: Sovegnon Pierre Marie , Akoton Romaric , Stopard Isaac J. , Churcher Thomas S. , McCall Philip J. , Ranson Hilary , Foster Geraldine M. , Djogbénou Luc Salako
Published: July 2024

Background

The widespread use of insecticide-treated nets (ITNs) has significantly contributed to the reduction in malaria cases and deaths observed across Africa. Unfortunately, this control strategy is threatened by the rapid spread of pyrethroid resistance in malaria vectors. Dual-active-ingredient insecticidal nets are now available to mitigate the impact of pyrethroid resistance. To facilitate evidence-based decisions regarding product selection in specific use settings, data are needed on the efficacy of these different nets against local mosquito populations.

Methods

Two experimental hut trials were performed in Za-Kpota, southern Benin in 2021 to evaluate the performance of Interceptor G2 (BASF), Royal Guard (Disease Control Technologies) and PermaNet 3.0 (Vestergaard Frandsen), all dual-active-ingredient bednets, in comparison to untreated or standard pyrethroid-treated bednets, against free-flying wild Anopheles gambiae mosquitoes. The performance of some of these next-generation nets was compared to the same type of nets that have been in use for up to 2 years. Mosquitoes collected in the huts were followed up after exposure to assess the sublethal effects of treatments on certain life-history traits.

Results

The predominant species in the study site was Anopheles gambiae sensu stricto (An. gambiae s.s.). Both Anopheles coluzzii and An. gambiae s.s. were resistant to pyrethroids (deltamethrin susceptibility was restored by piperonyl butoxide pre-exposure). In the experimental hut trials, the highest blood-feeding inhibition (5.56%) was recorded for the Royal Guard net, relative to the standard PermaNet 2.0 net (44.44% inhibition). The highest 72-h mortality rate (90.11%) was recorded for the Interceptor G2 net compared to the PermaNet 2.0 net (56.04%). After exposure, the risk of death of An. gambiae sensu lato (An. gambiae s.l.) was 6.5-fold higher with the Interceptor G2 net and 4.4-fold higher with the PermaNet 3.0 net compared to the respective untreated net. Lower mosquito mortality was recorded with an aged Interceptor G2 net compared to a new Interceptor G2 net. Oviposition rates were lower in mosquitoes collected from huts containing ITNs compared to those of untreated controls. None of the mosquitoes collected from huts equipped with Royal Guard nets laid any eggs.

Conclusions

The Royal Guard and Interceptor G2 nets showed a potential to significantly improve the control of malaria-transmitting vectors. However, the PermaNet 3.0 net remains effective in pyrethroid-resistant areas.

Graphical Abstract
Commentary on the “A multidisciplinary opioid-reduction pathway for robotic prostatectomy: outcomes at year one”
Authors: Zhu Binbin , Cao Angyang , Chen Yijun
Published: July 2024

Background

Opioid-sparing multimodal analgesia is increasingly emphasized for postoperative pain management. This commentary discusses a study by Manning et al. on an opioid reduction pathway for robotic prostatectomy.

Methods

We reviewed the Manning et al. study, which implemented a multidisciplinary opioid reduction pathway and compared outcomes before and after pathway implementation. Outcomes included opioid use, pain scores, antiemetic use, length of stay, and readmissions.

Results

The study found reduced opioid consumption, lower antiemetic use, shorter length of stay, and similar pain scores after pathway implementation. However, the pre-post-study design has limitations in attributing causality to the pathway itself. Key confounders were not fully accounted for. The clinical significance of the small reduction in length of stay is also questionable.

Conclusions

This commentary highlights important limitations of the Manning et al. study, including the retrospective design, potential confounding factors, small effect size, and lack of long-term outcomes. While the study provides early evidence for a multidisciplinary opioid reduction approach, further rigorous prospective research is needed to confirm the observed benefits and long-term impacts. Additional focus on direct opioid consumption, equivalent analgesia assessment, and clinically meaningful outcomes is warranted.
Survival after thermal ablation versus wedge resection for stage I non-small cell lung cancer < 1 cm and 1 to 2 cm: evidence from the US SEER database
Authors: Yim Shelly , Lin Wei Chan , Liu Jung Sen , Yen Ming Hong
Published: July 2024

Background

This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm.

Methods

Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures.

Results

Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09–1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96–1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10–1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size < 1 cm.

Conclusions

In patients with stage I NSCLC and tumor size < 1 cm, thermal ablation has similar OS and CSS with wedge resection.
The role of national nutrition programs on stunting reduction in Rwanda using machine learning classifiers: a retrospective study
Authors: Munyemana Jacques , Kabano Ignace H. , Uzayisenga Bellancile , Cyamweshi Athanase Rusanganwa , Ndagijimana Emmanuel , Kubana Emmanuel
Published: July 2024

Background

In Rwanda, the prevalence of childhood stunting has slightly decreased over the past five years, from 38% in 2015 to about 33% in 2020. It is evident whether Rwanda's multi-sectorial approach to reducing child stunting is consistent with the available scientific knowledge. The study was to examine the benefits of national nutrition programs on stunting reduction under two years in Rwanda using machine learning classifiers.

Methods

Data from the Rwanda DHS 2015–2020, MEIS and LODA household survey were used. By evaluating the best method for predicting the stunting reduction status of children under two years old, the five machine learning algorithms were modelled: Support Vector Machine, Logistic Regression, K-Near Neighbor, Random Forest, and Decision Tree. The study estimated the hazard ratio for the Cox Proportional Hazard Model and drew the Kaplan–Meier curve to compare the survivor risk of being stunted between program beneficiaries and non-beneficiaries. Logistic regression was used to identify the nutrition programs related to stunting reduction. Precision, recall, F1 score, accuracy, and Area under the Curve (AUC) are the metrics that were used to evaluate each classifier's performance to find the best one.

Results

Based on the provided data, the study revealed that the early childhood development (ECD) program (p-value = 0.041), nutrition sensitive direct support (NSDS) program (p-value = 0.03), ubudehe category (p-value = 0.000), toilet facility (p-value = 0.000), antenatal care (ANC) 4 visits (p-value = 0.002), fortified blended food (FBF) program (p-value = 0.038) and vaccination (p-value = 0.04) were found to be significant predictors of stunting reduction among under two children in Rwanda. Additionally, beneficiaries of early childhood development (p < .0001), nutrition sensitive direct support (p = 0.0055), antenatal care (p = 0.0343), Fortified Blended Food (p = 0.0136) and vaccination (p = 0.0355) had a lower risk of stunting than non-beneficiaries. Finally, Random Forest performed better than other classifiers, with precision scores of 83.7%, recall scores of 90.7%, F1 scores of 87.1%, accuracy scores of 83.9%, and AUC scores of 82.4%.

Conclusion

The early childhood development (ECD) program, receiving the nutrition sensitive direct support (NSDS) program, focusing on households with the lowest wealth quintile (ubudehe category), sanitation facilities, visiting health care providers four times, receiving fortified blended food (FBF), and receiving all necessary vaccines are what determine the stunting reduction under two among the 17 districts of Rwanda. Finally, when compared to other models, Random Forest was shown to be the best machine learning (ML) classifier. Random forest is the best classifier for predicting the stunting reduction status of children under two years old.
Exploring barriers and solutions to consumer involvement in health service research using a nominal group technique
Authors: Ryan Laura , Wenke Rachel , Carlini Joan , Weir Kelly A. , Shapiro Margaret , Baglot Noela , Tobiano Georgia , Sargeant Sally , Hattingh Laetitia
Published: July 2024

Background

Consumer involvement in health research is when patients, their families and caregivers work with researchers on research projects. Despite the growing expectation for health services to facilitate the involvement of consumers in research, the practical integration of this approach is an ongoing process, with limited research conducted into how Australian health services can support this practice. This study explored consumer perspectives on the barriers and solutions to enabling consumer involvement in research within an Australian tertiary hospital and health service, and staff perspectives on the solutions to facilitating consumer involvement. A prior survey had identified barriers to consumer involvement from the staff perspective. The broad aim was to inform the development of a framework to help promote consumer involvement in research within the health service.

Methods

A Nominal Group Technique (NGT) was utilised with groups comprised of health service consumers and staff. Three health consumers were co-researchers in the full life-cycle of this study and are included as authors.

Results

Ten consumers and 14 staff participated across three sessions ranging from one to three hours. For consumers, barriers to their involvement were grouped into seven domains: (1) lack of connection with researchers/research projects, (2) low research literacy, (3) structural barriers, (4) lack of acknowledgement, (5) implementation challenges, (6) inadequate information provision, and (7) representation concerns. Solutions to enabling involvement were grouped into five domains: (1) support to connect with researchers/research projects, (2) adequate information provision, (3) incentive for involvement, (4) acknowledgement, and (5) balanced representation. Staff ideas for solutions were grouped into five domains: (1) support to connect with consumers, (2) support to involve consumers, (3) access to funds to remunerate consumers, (4) more time to involve consumers, and (5) staff training.

Conclusion

Through an NGT methodology, this study delivered a nuanced comprehension of perspectives on involving consumers in research from both health service consumers and staff. These findings serve as a foundation for identifying strategies that foster enhanced and refined relationships between consumers and researchers, advancing the collaborative landscape in health research. The findings from this project offer valuable strategies for researchers to better engage consumers in research and for consumer groups to enhance their involvement. Additionally, these insights could be used by other health services to advocate for essential resources.
Automated prediction of response to neoadjuvant chemotherapy from digitized H&E slides of pre-treatment core needle biopsies in germline BRCA carriers with HER2-negative breast cancer (TBCRC 031).
Authors: Tung Nadine M. , Schnitt Stuart J. , Garber Judy Ellen , Mukhopadhyay Satabhisa , Dasgupta Tathagata , Bunnell Craig A.
Published: July 2024

605

Background: The INFORM trial, a phase II study of neoadjuvant cisplatin (C) vs doxorubicin-cyclophosphamide (AC) in germline BRCA carriers with HER2-negative breast cancer, demonstrated no difference in response rates between the two arms. The aim of the current study was to determine if quantification of features related to the immune response, proliferative status, and key cell cycle deregulation extracted from digital images of H&E-stained pre-treatment core needle biopsies (CNB) could distinguish patients with a good response to neoadjuvant chemotherapy (NAC) (RCB 0,1) from those with a poor response (RCB 2,3). Methods: CNBs (n=92 with RCB scores available) scanned at 40x on a Hamamatsu Nanozoomer scanner were evaluated using the 4D QPOR platform to generate digital biomarkers as continuous indices measuring immune, proliferation, and key cell cycle deregulation signatures. 96% (88/92) could be analyzed successfully. All biomarkers generated were based on an algorithm that combines statistical physics and tumor biology features to quantify cell cycle aberrations, from H&E whole slide images alone, and were evaluated at their median cut-off to determine if they could identify responders to NAC. Other QPOR indices were analyzed using AUC-ROC to further reduce false positive (FP) and false negative (FN) rates. Pathology review was done on FP and FN cases to determine if they were associated with any specific features. Results: The QPOR Immune Heterogeneity Index (IHI), measuring intra-slide spatial heterogeneity of stromal tumor infiltrating lymphocytes (sTIL), was predictive of RCB 0,1 with greater heterogeneity associated with worse response. IHI identified patients with RCB 0,1 with overall accuracy = 65%, sensitivity = 63%, specificity = 66%, PPV = 62%, NPV = 67%. IHI performed better in predicting RCB 0,1 than pathologist-identified sTIL in the full cohort, TNBC, and BRCA1 sub-cohorts (two sample Wilcoxon test p-value = 0.013, 0.047 and 0.013 respectively, with nonsignificant p-values for sTIL). IHI combined with a proliferative index and a G1S phase deregulation index (CmbI) was predictive of RCB 0,1 with improved accuracy over that of any of these features alone (overall accuracy = 80%, sensitivity = 71%, specificity = 87%, PPV = 83%, NPV = 77%, OR = 16.51 95% CI: 10.05-1.14, kappa = 0.59 (p<0.00001), AUC=0.80 95% CI: 0.71-0.89). CmbI better predicted RCB 0,1 for both AC and C arms (AUC=0.83 95% CI: 0.71-0.96 and 0.77 95% CI: 0.63-0.91, OR = 23.22 95% CI: 148.88-5.10 and 6.47 95% CI: 28.08-1.72, respectively) than IHI alone. Conclusions: QPOR-generated immune, proliferative, and key cell cycle signature indices individually, and more strongly in combination, appear predictive of NAC response in germline BRCA carriers with HER2-negative breast cancers.
Survival outcomes and treatment patterns by tumor subtype (TS) in stage III inflammatory and non-inflammatory breast cancer (BC).
Authors: Leone Jose Pablo , Leone Julieta , Nakhlis Faina , Schlam Ilana , Hirko Kelly , Hazra Aditi , Bellon Jennifer Ruth , Vallejo Carlos Teodoro , Lin Nancy U. , Tolaney Sara M. , Lynce Filipa
Published: July 2024

607

Background: Inflammatory BC (IBC) is an aggressive form of BC for which trimodality therapy (TMT) is standard. We examined TMT use and compared BC-specific survival (BCSS) and overall survival (OS) between IBC and non-IBC within TS. We also examined survival changes over time. Methods: We evaluated patients (pts) with stage III BC diagnosed 2010 - 2020, using Surveillance, Epidemiology and End Results data. The cohort was categorized as IBC (T4d), and non-IBC. TMT included neoadjuvant systemic therapy (NAST), mastectomy, dissection of ≥6 axillary nodes, and adjuvant radiation (RT). We evaluated BCSS and OS between IBC and non-IBC stratified by TS. Comparisons were made in stratified multivariable Cox models providing adjusted hazard ratios (aHzR) with 95% confidence intervals (CI). Results: We included 3,227 IBC and 44,475 non-IBC pts, with a median follow up of 70 and 68 months, respectively. Median age was 57 years for both. As compared with non-IBC, IBC pts were more often White, single, and had more grade III and less HR+/HER2- (all p<0.001). Individual treatments in IBC vs non-IBC included: mastectomy (73.5% vs 68.1%, p<0.001); dissection of ≥6 axillary nodes (54.9% vs 71.6%, p<0.001); RT (58.4% vs 60%, p=0.07), chemotherapy (87.1% vs 78.7%, p<0.001), NAST (58.4% vs 32.7%, p<0.001); respectively. Overall rate of TMT for IBC was 31.4% and decreased from 33.9% in 2010 to 24.2% in 2020 (p for trend = 0.014). Stage III IBC pts had worse BCSS than non-IBC in each TS (table). Pts with T4 tumors had similar differences but with smaller magnitude (table). We observed improvements in BCSS between 2010-2020 for stage III non-IBC (aHzR=0.98 per year, p<0.001), non-IBC T4 only (aHzR=0.97 per year, p<0.001), and stage III non-IBC treated with TMT (aHzR=0.97 per year, p=0.007). In contrast, there were no improvements in BCSS between 2010-2020 for IBC pts overall (aHzR=1.02 per year, p=0.12) or IBC pts treated with TMT (aHzR=1.03 per year, p=0.25). OS showed similar results to those from BCSS across all analyses. Conclusions: Stage III IBC has worse BCSS and OS than stage III non-IBC within each TS. The rate of TMT for IBC is low and decreased significantly over time, though the completeness of treatment data is a limitation. BCSS and OS did not improve over time for IBC pts, even when treated with TMT; whereas BCSS and OS improved for non-IBC. [Table: see text]
Differentiating pancreatic cancer via cfDNA levels in liquid biopsies.
Authors: Riauka Romualdas , Kupcinskaite-Noreikiene Rita , Grabauskyte Ingrida , Barauskas Giedrius , Gulbinas Antanas , Gruodyte Vakare , Jasukaitiene Aldona , Ignatavicius Povilas
Published: July 2024

e16344

Background: Pancreatic cancer remains an aggressive and highly lethal disease, exhibiting an overall 5-year survival rate of merely 10%, among the lowest compared to other oncological conditions. The absence of early and effective diagnostic tools hampers the management of pancreatic cancer (PC) patients, leading to compromised quality of life and treatment outcomes. Liquid biopsies, a relatively novel diagnostic method, enable non-invasive sampling of tumor materials. Specific genetic information, particularly changes in circulating free DNA (cfDNA) levels, is believed to forecast poorer tumor differentiation, a more aggressive disease course, faster relapse, and potential use as an early cancer diagnostic marker or for evaluating treatment efficacy. Methods: This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed PC, without prior treatment and patients with chronic pancreatitis (control group), admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and November 2023 were included in this study. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Results: Throughout the study period, 55 patients were included (47 with PC and 8 with chronic pancreatitis). cfDNA levels exhibited significant elevation in PC patients compared to those with chronic pancreatitis (p = 0.037; median (minimum – maximum): 46.5 ng/ml (4 – 768) vs 21.9 ng/ml (8.56 – 138.4) accordingly). The determined cut-off value for cfDNA levels distinguishing PC from chronic pancreatitis was 23.65 ng/ml (Area Under the Curve (AUC) = 0.73, sensitivity = 0.851, specificity = 0.625. Nevertheless, no distinctions in cfDNA levels were noted concerning tumor localization, size, differentiation, spread, or survival rates. Conclusions: Liquid biopsies and alterations in cfDNA levels could aid in distinguishing pancreatic cancer from benign inflammatory diseases like chronic pancreatitis. Nonetheless, further studies and experiments are necessary for comprehensive validation.
A multicenter, randomized controlled phase 2b trial of survivin vaccine SurVaxM plus adjuvant temozolomide for newly diagnosed glioblastoma (SURVIVE).
Authors: Ahluwalia Manmeet Singh , Ciesielski Michael J , Reardon David A. , Butowski Nicholas A. , Aiken Robert , Venur Vyshak , Abad Ajay Prakash , Mechtler Laszlo , Peereboom David M. , Odia Yazmin , Sinicrope Kaylyn , Boockvar John A , Brenner Andrew J. , Barbaro Marissa , Ozair Ahmad , Belal Ahmed , Qiu Jing-Xin , Khosla Atulya Aman , Casucci Danielle M. , Fenstermaker Robert Alan
Published: July 2024

TPS2099

Background: Newly-diagnosed glioblastoma (nGBM) has a dismal prognosis with a median overall survival (OS) of nearly 16 months. nGBM cells have high expression of tumor-associated survivin protein. Survivin, localized to the cell surface through presentation by MHC class I molecules, is recognized by antibodies and cytotoxic T-lymphocytes (CTLs). A phase 2a trial (NCT02455557) demonstrated a median OS of 25.9 months in nGBM from a 15-amino acid-peptide-conjugate vaccine (SurVaxM), which also stimulated production of survivin-directed antibodies and anti-tumor CTL. This phase 2b randomized controlled trial (RCT) aims to further investigate the efficacy and safety of SurVaxM and adjuvant temozolomide for nGBM. Methods: This multicenter, placebo-controlled, investigator- and patient-blinded, in-progress RCT randomizes nGBM patients receiving standard of care to either SurVaxM (arm A) or saline placebo (arm B) in a 3:2 ratio at 11 sites. Included patients have age ≥18 years, normal organ function, Karnofsky Performance Status (KPS) ≥70, receiving surgical resection with residual MRI contrast enhancement of ≤1 cm3 within 72 hours of resection, and adjuvant temozolomide (TMZ) therapy. Patients with recurrent, multicentric, brainstem- or cerebellar-origin GBM are excluded, as well as patients on tumor-treating fields or other immunotherapies. All patients undergo 3 phases: (1) vaccine priming (VP) phase, starting within 4 weeks after completion of chemoradiation, where 4 doses of SurVaxM or Placebo are administered every 2 weeks; (2) adjuvant TMZ phase, started after ≥1 VP dose; and (3) vaccine maintenance phase, started 8 weeks after VP, with SurVaxM or placebo given every 8 weeks. TMZ phase overlaps with VP and VM phases. The primary endpoint is median OS. Assuming a 1-year survival rate of 75% in the SurVaxM arm, comparable to median OS in early phase trials, and 60% in the control arm, the required sample size consists of 137 in the SurVaxM arm and 91 in the control arm for a total sample size of 228. Accounting for dropout, the study aims to enroll 246 patients. A log-rank test stratified by KPS (70-80 and 90-100), MGMT status (methylated and unmethylated), and IDH status (mutant and wild-type) will be used for analysis. Secondary endpoints per study arm are survival at 15, 18, and 24 months, median progression-free survival, toxicity, and progression-free survival at 3, 6, and 12 months. A single sequential OS-driven interim analysis is planned when 50% of OS events (deaths) occur. 205 patients have been enrolled as of January 2024. Clinical trial information: NCT05163080 .
Diagnostic and Practical Challenges in Applying National Comprehensive Cancer Network Guidelines for Suspected Pathogenic TP53 Mosaicism
Authors: Nathan Daniel I. , Brander Tehilla , Gold Julie , Paul Deborah , Klein Paula , Cheng Kit , Liu Johnson M. , Marcellino Bridget K.
Published: July 2024

Benefits and limitations in using NCCN guidelines to distinguish TP53 CH from mosaic LFS.
Ο ρόλος της θυρεοειδικής ορμόνης ως προστατευτικής παρέμβασης στην ψυχρή ισχαιμική βλάβη που προκαλείται στο μυοκάρδιο από την καρδιοπληγία
Authors: Κουνατίδης Δημήτριος
Published: July 2024

Η μεταμόσχευση καρδιάς αποτελεί τη θεραπεία εκλογής στην τελικού σταδίου καρδιακή ανεπάρκεια, με τη στατική ψυχρή καρδιοπληγία να είναι η μέθοδος εκλογής στη συντήρηση του καρδιακού αλλομοσχεύματος. Ωστόσο, η παρατεταμένη διατήρηση της καρδιάς του δότη σε συνθήκες ψύξης σχετίζεται με αυξημένο κίνδυνο πρώιμης δυσλειτουργίας. Αυτό αποτελεί απόρροια της υποκείμενης ισχαιμίας, αλλά και της βλάβης που εμφανίζει το μυοκάρδιο του δότη μετά την επαναιμάτωση. Από την άλλη πλευρά, τα τελευταία χρόνια διαπιστώνεται ένας σημαντικός περιορισμός του αριθμού των διαθέσιμων μοσχευμάτων, γεγονός το οποίο καθιστά επιτακτική την ανεύρεση εναλλακτικών πηγών. Αυτό μπορεί να επιτευχθεί αφενός με τη διεύρυνση των αποδεκτών κριτηρίων, που χαρακτηρίζουν ένα μόσχευμα ως κατάλληλο για χρήση, και αφετέρου με την αναζήτηση νεότερων μεθόδων, που θα καταστήσουν το προς χρήση μόσχευμα περισσότερο λειτουργικό. Η νορμοθερμική διαπότιση αποτελεί μια τέτοια, νεότερη και πολλά υποσχόμενη τεχνική, που βασίζεται στη χορήγηση παραγόντων με τεκμηριωμένη καρδιοπροστατευτική δράση. Η θυρεοειδική ορμόνη (ΤΗ) χρησιμοποιείται παραδοσιακά στη μεταμόσχευση καρδιάς, λόγω των ευεργετικών επιδράσεων που αυτή εμφανίζει στον τραυματισμό του μυοκαρδίου από την ισχαιμία/επαναιμάτωση, ενώ παράλληλα έχει ευνοϊκή επίδραση στην καρδιακή αναδιαμόρφωση (remodeling). Πρόσφατα, η χρήση της θυρεοειδικής ορμόνης κατά τη νορμοθερμική διαπότιση έδειξε ένα ευνοϊκό προφίλ στην καρδιακή λειτουργία, ως συνέπεια των επιδράσεων της ορμόνης σε μονοπάτια, τα οποία σχετίζονται με τη φλεγμονή, την απόπτωση και την αγγειογένεση, αντίστοιχα. Στο γενικό μέρος της παρούσας διδακτορικής διατριβής, το οποίο διακρίνεται σε 2 κύρια τμήματα, θα αναλυθούν τα κύρια προβλήματα στη μεταμόσχευση καρδιάς στη σύγχρονη κλινική πρακτική, οι κύριες μέθοδοι συντήρησης του καρδιακού αλλομοσχεύματος αλλά και οι μηχανισμοί μέσω των οποίων η θυρεοειδική ορμόνη ασκεί την προστατευτική της δράση στο μυοκάρδιο. Στο δεύτερο, ειδικό μέρος, αναλύεται το πειραματικό πρωτόκολλο της παρούσας διατριβής, η μοριακή και στατιστική ανάλυση, ενώ τέλος γίνεται μια συζήτηση ως προς τον ρόλο της θυρεοειδικής ορμόνης στη συντήρηση του καρδιακού μοσχεύματος με τη μέθοδο της νορμοθερμικής διαπότισης.
Οδοντική φθορά και περιοδοντική κατάσταση σε Ελληνικό πληθυσμό ενηλίκων
Authors: Θεοδωρίδης Χάρης
Published: July 2024

Σκοπός: Η διερεύνηση επιδημιολογικών χαρακτηριστικών της οδοντικής φθοράς (ΟΦ) σε πληθυσμό Ελλήνων ενηλίκων και η μελέτη ενδεχόμενων συσχετίσεων αυτής με την περιοδοντική κατάσταση, αλλά και με κοινωνικούς και δημογραφικούς παράγοντες. Υλικά και Μέθοδοι: Το αρχειακό υλικό της μελέτης αφορά σε δείγμα 894 ατόμων που ανήκουν στις ηλικιακές ομάδες ενοδόντων εθελοντών 35-44 ετών (Ομάδα Ι, Ν=531) και 65-74 ετών (Ομάδα ΙΙ, Ν=363), όλοι κάτοικοι Β. Ελλάδας, και οι οποίοι υποβλήθηκαν σε κλινική εξέταση και συμπλήρωση ερωτηματολογίου, σύμφωνα με το πρωτόκολλο του ΠΟΥ για Εθνικές τροχιοδεικτικές Έρευνες. Αξιολογήθηκε ο δείκτης TWI (Tooth Wear Index), αλλά και περιοδοντικοί δείκτες όπως ο δείκτης απώλειας πρόσφυσης (ΑL), ο CPI (Community Periodontal Index) και δείκτες σχετικά με την παρουσία μικροβιακής πλάκας (DI) και τρυγιακών εναποθέσεων (CI). Με τη χρήση ερωτηματολογίου καταγράφτηκαν κοινωνικά και δημογρα-φικά χαρακτηριστικά των υπό εξέταση Ομάδων. Η στατιστική ανάλυση, βασι-σμένη στους σκοπούς της μελέτης, έλαβε χώρα σε επίπεδο οδοντικής επιφά-νειας, αλλά και σε επίπεδο ατόμου. Αποτελέσματα: Η Οδοντική Φθορά (ΟΦ) μετρήθηκε σε περίπου 40.000 οδοντικές επιφάνειες που εξετάστηκαν στους εθελοντές και των δύο ομάδων. Από όλες τις επιφά-νειες, αυτές που εμφάνισαν τη μεγαλύτερη μέση ΟΦ ήταν οι κοπτικές των προσθίων δοντιών, με τις χαμηλότερες τιμές ΟΦ να καταγράφονται στις χειλικές επιφάνειες των άνω προσθίων. Στην Ομάδα Ι, εντοπίστηκε σημαντική θετική συσχέτιση του μέσου TWI και της περιοδοντικής κατάστασης, όπως αυτή καταγράφτηκε με τους μετρούμενους δείκτες ΑL, CPI, DI, CI, ενώ στην Ομάδα ΙΙ o δείκτης TWI συσχετίστηκε σημαντικά με τους δείκτες ΑL, DI και CI. Επι-πρόσθετα, ανευρέθηκε συσχέτιση του TWI με την ηλικία και το φύλο των εθε-λοντών σε αμφότερες τις ηλικιακές ομάδες. Συμπεράσματα: Η ΟΦ συνιστά διαδεδομένο φαινόμενο στις τάξεις των Ελλήνων μεσηλίκων και υπερηλίκων, με τους τελευταίους να παρουσιάζουν τουλάχιστον μία φθαρμένη οδοντική επιφάνεια σε σχεδόν καθολικό βαθμό. Η ΟΦ σχετίζεται σημαντικά με την περιοδοντική κατάσταση των συμμετεχόντων και στις δύο ηλικιακές ομάδες της μελέτης. Επίσης, το ανδρικό φύλο, και η επιμέρους αύξηση της ηλικίας των συμμετεχόντων αποτελούν παράγοντες συνδεδεμένους με επιδείνωση της ΟΦ.
The potential role of Vascular Endothelial Growth Factor for hepatocellular carcinoma screening: a systematic review
Authors: Masadah Rina , Qanitha Andriany , Hanifah Rif'at , Al Atsari Muhammad Azka , Nurdahlia Andi , Muiz Faturrahman , Yusuf Rezky Aulia
Published: July 2024

Background Hepatocellular Carcinoma (HCC) stands as the third most fatal malignancy worldwide, accounting for over 830,000 fatalities annually. This pressing concern has spurred extensive research into potential early diagnostic biomarkers, with a particular focus on the role of vascular endothelial growth factor (VEGF) in recognizing angiogenesis within HCC. VEGF offers an intricate insight into the angiogenic processes, among its multifaceted advantages. Methods We systematically curated articles from PubMed and Epistemonikos, concentrating on the determination of VEGF’s diagnostic cutoff value, sensitivity, and specificity for HCC. Employing the PRISMA 2020 flowchart, we meticulously delineated the process of article selection. Results In total, our review encompasses nine studies, encompassing 576 HCC patients, subject to qualitative analysis. The collective findings indicate that the specificity of VEGF outweighs its sensitivity, indicating its aptitude in distinguishing HCC from both a healthy population and other high-risk conditions, most notably in comparison with these high-risk conditions. Specificity holds pivotal significance as a preferred parameter for a screening test, endorsing the prospective utility of VEGF in HCC screening. Conclusions For individuals, especially those within the normal alpha-fetoprotein range, VEGF may serve as a viable alternative for HCC screening, facilitating the differentiation of this condition from other high-risk conditions.
Is there a link between gastroesophageal reflux disease and physical activity?
Authors: Puchała Justyna , Basiura Karolina , Starzomska Dominika , Gajdzińska Natalia , Rymaszewska Katarzyna , Rostkowska Weronika , Salwa Adam , Rutkowski Wojciech , Rzepka Maciej , Sztuba Karolina
Published: July 2024

Aim of study
The purpose of this review is to examine the impact of physical activity on the course of gastroesophageal reflux disease (GERD) and to provide an overview of the disease based on current literature.
Materials and Methods
A comprehensive literature search was conducted using the Medline/PubMed database to identify relevant studies. Additionally, reference lists of included articles were manually searched to identify further relevant studies. Data extraction was performed independently by two reviewers using a standardized form.
Results
GERD is a chronic condition characterized by the reflux of stomach contents into the esophagus, affecting an estimated 20% of the global population. Pathophysiological mechanisms include transient lower esophageal sphincter relaxation, hiatal hernia, and delayed gastric emptying. Physical activity has a dual impact on GERD; while moderate exercise can aid in symptom management by promoting weight loss and improving gastric emptying, high-intensity activities may exacerbate symptoms due to increased intra-abdominal pressure.
Conclusions
GERD is a prevalent chronic condition that significantly impacts quality of life. Effective management requires a multifaceted approach, including lifestyle modifications, pharmacotherapy, and in severe cases, surgical intervention. Moderate physical activity can be beneficial for symptom management, but high-intensity exercise may worsen symptoms. Health professionals should emphasize patient education and tailored treatment strategies to improve outcomes for GERD patients.
Level of knowledge of Stereotypic Movement Disorders among paediatric population. An update on proper differential diagnosis and management including physical exercise approach - comprehensive literature review
Authors: Jachymek Anna , Gmitrzuk Julia , Malinka Zuzanna , Wiśniewska Katarzyna , Opatowska Martyna , Jakubiec Joanna , Kucharski Tomasz , Piotrowska Marta
Published: July 2024

Stereotypies stand out as the most debated aspect within the spectrum of repetitive behaviors observed in childhood, which encompass mannerisms,habits, compulsions, tics, and other sudden movements. Stereotypies refer to a repetitive, persistent, often rhythmic pattern of non-purposeful motor actions that may disrupt social interaction, academic performance, or other daily activities, and can potentially lead to physical harm. Many young children exhibit stereotyped behaviors, such as thumb sucking. In older children and adults, repetitive behaviors like finger tapping or drumming, self-stimulatory actions (e.g., masturbation) or leg shaking, may occur in response to boredom. These behaviors differ from Stereotyped Movement Disorder because they do not significantly interfere with daily activities nor cause self-inflicted bodily injury severe enough to warrant independent clinical attention. Stereotyped movements are commonly categorized into two groups: primary and secondary, based on the presence of additional signs or symptoms. The former are perceived as physiological, as opposed to the latter, which are considered pathological. There is growing evidence supporting a neurobiological mechanism despite some perceiving stereotypic movements as behaviors aimed at modifying arousal states. Both behavioral and pharmacological treatments have been employed with mixed results, hence, there is a need for further research in this area, including physical exercise. Conclusively, a more profound comprehension of the underlying risk factors and biology of motor stereotypies will eventually bring us nearer to developing more effective targeted therapies, which will alleviate the suffering of children who are affected.
EL PROCURADOR CRIOLLO ALONSO DE OVALLE EN ROMA. UNA “HISTÓRICA RELACIÓN” DE GUERRA Y PAZ, SIGLO XVII
Authors: Gaune Corradi Rafael , Domeyko Josefina
Published: July 2024

En este artículo abordaremos a un mediador –el procurador jesuita criollo Alonso de Ovalle– y su movilidad entre América, España y Roma durante la segunda mitad del siglo XVII. Vincularemos ese mediador a un agente de saberes y redes específicas de conocimiento. De este modo, el estudio de caso que presentamos nos permite estudiar cómo un libro publicado sobre Chile en la Roma barroca, la Histórica Relación del Reino de Chile, abre posibilidades de análisis sobre la importancia del procurador como un mediador y agente de circulación que permite dar a conocer en Europa y describir las vicisitudes de la guerra y la paz de un confín de la Monarquía de España.
DE ZHANGZHOU A FILIPINAS: UNA RUTA DE APROVISIONAMIENTO DEL GALEÓN DE MANILA EN LA PRIMERA GLOBALIZACIÓN.
Authors: Meng Zhou
Published: July 2024

Este estudio investiga la ruta marítima histórica entre Zhangzhou y Manila durante los siglos XVI y XVII, explicando la navegación comercial que aprovechaba los monzones para llegar a Filipinas e intercambiar mercancías chinas por plata española. Se examinan detalladamente los términos náuticos y métodos de orientación utilizados por los marineros chinos, así como las unidades de tiempo y recorrido empleadas en la navegación. Se reconstruye la ruta analizando fuentes primarias y mapas menos conocidos por la historiografía occidental, incluyendo el Dongxiyangkao y el Shunfeng Xiangsong. Se discuten las variaciones en la duración del viaje según las condiciones meteorológicas y se comparan las descripciones de la ruta que aparecen en diferentes fuentes históricas
LA SALUD DE LA PATRIA ESTÁ EN PELIGRO”: ENFERMEDADES Y EPIDEMIAS DURANTE LA GUERRA DE INDEPENDENCIA EN EL PERÚ.
Authors: Morán Ramos Daniel , Yarango Velásquez Jesús , Carcelén Reluz Carlos , Pérez Valdivia Javier
Published: July 2024

En el contexto de la conmemoración del bicentenario de la independencia peruana, encontramos una diversidad de líneas temáticas que merecen mayores exploraciones. Bajo esa premisa, el objetivo central de esta investigación es analizar el impacto de las enfermedades y epidemias durante la guerra de Independencia en el Perú en base a una serie de testimonios médicos y relatos de viajeros de la época. En ese sentido, este trabajo busca sumarse a una serie de investigaciones que contribuyen a conocer la situación de la salud pública en los últimos años del dominio español en el Perú, y las repercusiones que tuvieron las enfermedades y epidemias durante y después de la guerra de independencia.
EL RELICARIO DE SAN HERMIÓN Y LAGOS DE MORENO, 1791-2019.
Authors: Carbajal López David
Published: July 2024

El relicario de San Hermión mártir llegó a la villa de Lagos en 1791. Desde entonces lo mismo ha sido objeto de devoción, capaz de conceder milagros y “favores”, que ha dado su nombre a hijos e hijas de las familias laguenses. Entre los siglos XX y XXI, además, se ha consolidado también como un objeto cultural fuente de leyendas, evocador de memoria y motivo importante de visitas turísticas para la ciudad.
LA LLEGADA DE LOS JUDÍOS HÚNGAROS A URUGUAY DURANTE Y DESPUÉS DE LA SHOÁ.
Authors: Facal Santiago Silvia
Published: July 2024

La llegada de los judíos de Hungría a Uruguay se produjo entre los años 1920 y 1957. En este estudio nos focalizamos únicamente en analizar las vivencias tanto en Hungría como en Uruguay de quienes llegaron durante y después de la Shoá, Es decir, de quienes sufrieron la persecución y el intento de exterminio por el hecho de ser judíos y de quienes sobrevivieron a este.
Jurisdiction over International Crimes: International Criminal Court and Other Ways of Ending Impunity
Authors: Valusha Irina , van den Boom Maryna
Published: July 2024

The book addresses the challenges and limitations in prosecution of individuals who committed crimes under international law. The individual criminal responsibility is broadly recognized and based on the understanding of the feasibility of such accountability in the present era. The Nuremberg Trials in 1946 marked a pivotal moment, establishing the first international tribunal for individuals and initiating a new chapter in international law’s pursuit of perpetrators threatening common values. The establishment of the permanent International Criminal Court (ICC) under the Rome Statute in 1998 and its operations since July 2002 show that its jurisdiction has not effectively curtailed the impunity of dictators, tyrants, and torture servants, especially in non-member States. Motivated by these shortcomings, the authors have analyzed the ICC’s procedural capacity to prosecute offenders from non member States to the Rome Statute and explored alternative jurisdiction modes over international crimes committed by individuals. The book advocates a broader application of the universal jurisdiction principle, recognizing the limitations of ad hoc criminal tribunals, hybrid courts, and the practical constraints of the ICC. The authors propose that, in addition to the ICC, international organizations and national states—especially those progressing toward the rule of law—can enhance the international justice system. Their suggestions include supporting civil society, establishing independent investigative mechanisms, maintaining human rights monitoring processes, and sharing best practices in investigating international crimes, including those covered by the Rome Statute, within national legal systems that apply the universal jurisdiction principle.
The role of mammals as carriers of pathogens with zoonotic potential
Authors: Tapia-Ramírez Gloria , Hernández-Aguilar Itandehui
Published: July 2024

The COVID-19 pandemic, which occurred 4 years ago, left behind a renewed interest in the discussion of the role of mammals as carriers of pathogens with zoonotic potential.  Previously, Han et al. (2016) stated that the mammalian orders with the highest number of species carrying this type of pathogens were Rodentia, Carnivora, and Chiroptera.  It was also noted that the areas of the Earth with the most mammalian carriers matched the areas with high biological biodiversity, i.e., those between latitudes 40° N and 40° S (Morse et al. 2012; Allen et al. 2017).  México is home to a high diversity of mammals (564 species; Sánchez-Cordero et al. 2014), and the orders mentioned above rank in the top 3 places in species richness (Rodentia 254, Chiroptera 144, and Carnivora 41).  So, it is important to know their role as reservoirs or carriers of etiological agents that can spread from animals to humans.  This is especially important because of the current loss rate of the original vegetation cover (for example, México lost 758,000 ha of tropical forest between 2002 and 2023; Global Forest Watch 2024) and because more people are moving into cities, which could make it easier for animals and people to come into contact with each other, potentially leading to a spillover. Given this scenario, this special issue of Therya Notes entitled “The Role of Mammals as Carriers of Pathogens with Zoonotic Potential” presents advances on the topic in the American continent through 11 notes focused on rodents, bats, and marsupials.
Molecular identification of Blastocystis sp. in urban rodents from México City
Authors: Martínez-Hernández Fernando , Ocampo Cervantes José Antonio , Tamayo-Aguilar Laura , Villalobos Guiehdani , Maravilla Pablo , Muñoz-García Claudia Irais , Rendón-Franco Emilio
Published: July 2024

Los roedores urbanos son animales sinantrópicos que desempeñan un papel fundamental como hospederos de las enfermedades transmitidas por roedores; sin embargo, existen escasos informes de protozoos zoonóticos intestinales en estos animales.  Por otro lado, Blastocystis sp. es el parásito zoonótico protozoario identificado con mayor frecuencia en estudios coprológicos de humanos a nivel mundial, y su presencia en roedores urbanos solo se ha documentado en algunos estudios.  El objetivo del presente estudio fue identificar a Blastocystis sp. mediante métodos moleculares en roedores sinantrópicos de la Ciudad de México.  Ochenta y cinco roedores (33 Mus musculus y 52 Rattus norvegicus) fueron atrapados en el parque público de Canal Nacional en la Ciudad de México, durante el otoño e invierno de 2020.  Se obtuvieron muestras de intestino grueso de todos los animales.  Se recuperó DNA de las muestras y se procesaron mediante la técnica de reacción en cadena de la polimerasa para la identificación de Blastocystis sp.  Veintiún muestras fueron positivas, por lo que la prevalencia fue del 32.7 % y 12.1 % para R. norvegicus y M. musculus, respectivamente.  Un reporte previo documentó una frecuencia del 31.5 % de Blastocystis sp. en pacientes de la Ciudad de México con trastornos gastrointestinales, y en concordancia con otros autores, nuestros resultados fortalecen que R. norvegicus podría ser utilizado como animal sinantrópico centinela; sin embargo, estudios que profundicen en la ecología humana y del roedor son necesarios para asegurar esto.