bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV self-testing in the real world is acceptable for many: post-test participant feedback from the GetaKit study in Ottawa, Canada
Authors: O’Byrne Patrick , Musten Alexandra , Ho Nikki 
Published: December 2022

Background: HIV self-testing is the latest strategy to improve access to testing, diagnosis and treatment. Such strategies are beneficial due to the improved individual- and population-level health outcomes that emerge from early HIV diagnosis. Aims: While most research shows that HIV self-testing is acceptable and feasible, yielding higher numbers of first-time testers and positivity rates, compared to clinic-based testing, little evidence exists outside low- and middle-income countries about such testing. Methods: We implemented GetaKit.ca, a website through which eligible participants could register for and obtain an INSTI® HIV self-testing to their home, and then report the result back. Results: Those who returned to the website were asked to complete a post-test survey, which had a low response rate (42%), but identified satisfaction scores of 92%. Notably, 5% of testers sought in-person care after ordering the self-test, and only 80% of participants agreed that the INSTI® HIV self-test was easy to use. Conclusions: Participants provided tangible solutions to improve this test, which we feel are easy to incorporate and essential to maintain HIV self-testing efforts.
Using the NINDS Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome on 4 Cohorts of Retired Contact Sport Athletes
Authors: Casson Ira R. , Viano David C. 
Published: December 2022

Background: A 2021 National Institute for Neurological Disorders and Stroke (NINDS) consensus panel proposed a set of clinical diagnostic criteria for traumatic encephalopathy syndrome (TES) and determined provisional levels of certainty for chronic traumatic encephalopathy (CTE) pathology based on neuropathological evidence. The panel suggested the criteria needed to be validated by clinical studies of living populations exposed to repetitive head impacts (RHIs). Hypothesis: As the consensus criteria were developed solely from neuropathologically diagnosed cases of CTE, we hypothesized that they may not be readily applicable to the clinical impressions developed from the histories and examination findings of living patients whose neuropathology was unknown. Study Design: We applied the consensus criteria to 4 groups of living retired contact sports athletes collected from previously published articles in the medical literature. Level of Evidence: Level 4. Methods: Clinical evidence from 4 groups of living retired athletes (boxers and American football players) with extensive RHI exposure was available. We used the NINDS consensus criteria to determine for each athlete whether or not they met the criteria for TES. For those who met the criteria, we determined their provisional level of certainty for CTE pathology. Results: Among all 80 subjects, the prevalence of TES was 21.3% (17 of 80), the prevalence of possible CTE was 12.5% (10 of 80), and the prevalence of probable CTE was 2.5% (2 of 80). Among the 45 retired football players, the prevalence of TES was 24.4% (11 of 45) and the prevalence of possible CTE was 17.7% (8 of 45). None of the retired football players met the criteria for probable CTE. Among the 35 total retired boxers (from all 3 groups), the prevalence of TES was 17.1% (6 of 35), the prevalence of possible CTE was 5.7% (2 of 35), and the prevalence of probable CTE was 5.7% (2 of 35). Conclusion: Applying the NINDS consensus criteria to this historical cohort of living retired athletes with extensive RHI exposure resulted in a relatively low prevalence of TES and possible/probable certainties of CTE pathology, which might suggest limitations on the sensitivity of the NINDS criteria. Clinical Relevance: Physicians are often asked by retired contact sports athletes and their families to determine if their clinical picture is related to TES and/or CTE. Physicians may turn to the NINDS consensus criteria for guidance in making such determinations. The data presented here may assist physicians in evaluating the reliability and validity of using the consensus criteria in living subjects.
Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes
Authors: Zhang Kai , Liu Dingyang , Yang Zhuanyi , Li Xuejun , Yang Zhiquan , He Xinghui 
Published: December 2022

Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12–0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93–0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.
Development of an innovative strategy to determine functioning attributed to health conditions in low-resource settings
Authors: Charumbira Maria Yvonne , Berner Karina , Blaauw Denric , Louw Quinette Abegail 
Published: December 2022

Objectives Rehabilitation is a health strategy that aims to reduce functioning problems. There is a lack of country-level data on the burden and type of functioning problems to inform service planning and management of patients’ rehabilitation needs, particularly at primary care level in low-resource settings. Health researchers need an application that automates synthesis of data extracted from several peer-reviewed publications to determine the most prevalent functioning problems compared across several health states. This article describes the journey leading to the conceptualization and development of the Rehab4all application and compares the application's performance to a standard desktop program. Methods A descriptive case study approach was used to report on the following steps involved in the development of the web-based Rehab4all application: (i) preliminary literature review to assess the evidence gap of country-level data on functioning problems comparable across several health states; (ii) an initial attempt to perform data extraction and synthesis in Excel; (iii) design and development of Rehab4all; (iv) piloting of the Rehab4all application; and (v) implementation of application with input data from South Africa and Zimbabwe. Results The Rehab4all application offers a feasible solution for synthesizing data from several peer-reviewed publications to provide information on context-specific, priority functioning problems at country level through the integrated global International Classification of Functioning, Disability and Health Framework (ICF). Conclusion This bespoke innovation provides impetus for further development, profile comparison and shared information between countries to co-develop strategies which can strengthen rehabilitation service delivery.
IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML
Authors: Perriello Vincenzo Maria , Rotiroti Maria Caterina , Pisani Ilaria , Galimberti Stefania , Alberti Gaia , Pianigiani Giulia , Ciaurro Valerio , Marra Andrea , Sabino Marcella , Tini Valentina , Spinozzi Giulio , Mezzasoma Federica , Morena Francesco , Martino Sabata , Salerno Domenico , Ashby Julian François , Wingham Brittany , Serafini Marta , Martelli Maria Paola , Falini Brunangelo , Biondi Andrea , Tettamanti Sarah 
Published: December 2022

Abstract
Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. Adoptive cell therapy by chimeric antigen receptor (CAR)-engineered T cells demonstrated a high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML, especially in elderly patients. To date, translation of CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen. CD123 and CD33 are the 2 most widely overexpressed leukemic stem cell biomarkers but their shared expression with endothelial and hematopoietic stem and progenitor cells increases the risk of undesired vascular and hematologic toxicities. To counteract this issue, we established a balanced dual-CAR strategy aimed at reducing off-target toxicities while retaining full functionality against AML. Cytokine-induced killer (CIK) cells, coexpressing a first-generation low affinity anti-CD123 interleukin-3–zetakine (IL-3z) and an anti-CD33 as costimulatory receptor without activation signaling domains (CD33.CCR), demonstrated a powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells and endothelial cells. The proposed optimized dual-CAR cytokine-induced killer cell strategy could offer the opportunity to unleash the potential of specifically targeting CD123+/CD33+ leukemic cells while minimizing toxicity against healthy cells.
Adaptation of Serious Illness Care Program to be delivered via telehealth for older patients with hematologic malignancy
Authors: LoCastro Marissa , Sanapala Chandrika , Mendler Jason H. , Norton Sally , Bernacki Rachelle , Carroll Thomas , Klepin Heidi D. , Watson Erin , Liesveld Jane , Huselton Eric , O’Dwyer Kristen , Baran Andrea , Flannery Marie , Kluger Benzi , Loh Kah Poh 
Published: December 2022

Abstract
Older patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) experience intense inpatient health care at the end-of-life stage. Early advance care planning may improve care at the end of life for patients with AML or MDS. The Serious Illness Care Program (SICP) is a multicomponent, communication intervention developed to improve conversations about values for patients with serious illnesses. The SICP has been shown to improve the quality and frequency of advance care planning discussions. We adapted the SICP for delivery via telehealth to older patients with AML or MDS. We conducted a single-center qualitative study of 45 participants (25 clinicians, 15 older patients with AML or MDS, and 5 caregivers). Participants, whether clinicians, patients, or caregivers, agreed that the SICP would help older patients with AML or MDS to share their personal values with their care team. Four qualitative themes emerged from our data: (1) serious illness conversations can be conducted via telehealth, (2) older patients have limited experience using technology but are willing and able to learn, (3) patients feel that serious illness conversations will help them understand their AML or MDS diagnosis and prognosis better, and (4) serious illness conversations should be common and routine, not extraordinary. The adapted SICP may provide older patients with AML or MDS an opportunity to share what matters most to them with their care team and may assist oncologists in aligning patient care with patient values. The adapted SICP is the subject of an ongoing single-arm pilot study at the Wilmot Cancer Institute (clinicaltrials.gov identifier: NCT04745676).
Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma
Authors: Epperla Narendranath , Switchenko Jeffrey , Bachanova Veronika , Gerson James N. , Barta Stefan K. , Gordon Max J. , Danilov Alexey V. , Grover Natalie S. , Mathews Stephanie , Burkart Madelyn , Karmali Reem , Sawalha Yazeed , Hill Brian T. , Ghosh Nilanjan , Park Steven I. , Bond David A. , Hamadani Mehdi , Fenske Timothy S. , Martin Peter , Malecek Mary-Kate , Kahl Brad S. , Flowers Christopher R. , Link Brian K. , Kaplan Lawrence D. , Inwards David J. , Feldman Andrew L. , Hsi Eric D. , Maddocks Kami , Blum Kristie A. , Bartlett Nancy L. , Cerhan James R. , Leonard John P. , Habermann Thomas M. , Maurer Matthew J. , Cohen Jonathon B. 
Published: December 2022

Abstract
The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using 3 large datasets (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource, (2) patients enrolled in the ALL Age Asthma Cohort/CALGB 50403, and (3) a multisitecohort of patients with MCL. Patients were a priori divided into 2 groups, 0 to 14 days (short DTI) and 15 to 60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. One thousand ninety-seven patients newly diagnosed with MCL and available DTI were included in the study. The majority (73%) had long DTI (n=797). Patients with short DTI had worse eastern cooperative oncology group performance status (ECOG PS ≥2), higher lactate dehydrogenase, bone marrow involvement, more frequent B symptoms, higher MCL International Prognostic Index (MIPI ≥6.2), and were less likely to receive intensive induction therapy than long DTI group. The median progression-free survival (2.5 years vs 4.8 years, p&lt;0.0001) and overall survival (7.8 years vs. 11.8 years, p&lt;0.0001) were significantly inferior in the short DTI group than the long DTI cohort and remained significant for progression-free survival and overall survival in multivariable analysis. We show that the DTI is an important prognostic factor in patients newly diagnosed with MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the patients newly diagnosed with MCL who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided.
Virtual consultations for patients with obstructive sleep apnoea: a systematic review and meta-analysis
Authors: Alsaif Sulaiman S. , Kelly Julia L. , Little Stuart , Pinnock Hilary , Morrell Mary J. , Polkey Michael I. , Murphie Phyllis 
Published: December 2022

BackgroundThe coronavirus disease 2019 pandemic has accelerated the adoption of virtual care strategies for the management of patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS).Research questionWhat is the effectiveness of virtual consultations compared to in-person consultations for the management of continuous positive airway pressure (CPAP) therapy in adult patients with OSAHS?MethodsA systematic review and meta-analysis (PROSPERO; CRD42022297532) based on six electronic databases plus manually selected journals was conducted in January 2022. Two researchers independently selected, quality appraised and extracted data. The co-primary outcomes were patient-reported sleepiness, assessed by the Epworth Sleepiness Scale (ESS), and reported cost-effectiveness.Results12 studies (n=1823 adults) were included in the review. Seven studies (n=1089) were included in the meta-analysis which showed no difference in the magnitude of improvement in patient-reported sleepiness scores between virtual and in-person consultations (mean difference −0.39, 95% CI −1.38–0.60; p=0.4), although ESS scores improved in both groups. Virtual care strategies modestly increased CPAP therapy adherence and were found to be less costly than in-person care strategies in the three Spanish trials that reported cost-effectiveness.ConclusionThe findings of this review suggest that virtual care delivered by telephone or video consultations is as effective as in-person consultations for improving subjective sleepiness in patients with OSAHS treated with CPAP. This clinical management strategy may also improve CPAP adherence without increasing the costs, supporting its potential as a follow-up management strategy, where patients prefer this approach.
Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study
Authors: Fenn Dominic , Lilien Thijs A. , Hagens Laura A. , Smit Marry R. , Heijnen Nanon F.L. , Tuip-de Boer Anita M. , Neerincx Anne H. , Golebski Korneliusz , Bergmans Dennis C.J.J. , Schnabel Ronny M. , Schultz Marcus J. , Maitland-van der Zee Anke H. , Brinkman Paul , Bos Lieuwe D.J. 
Published: December 2022

BackgroundChanges in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking.MethodsIn this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (H2O2), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres. Exposed and unexposed cells were compared using targeted and untargeted analysis. Breath samples of invasively ventilated intensive care unit patients (n=489) were collected on sorbent tubes and associated with the inspiratory oxygen fraction (FIO2) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry.ResultsIn the cell, headspace octane concentration was decreased after oxidative stress (p=0.0013), while the other VOCs were not affected. 2-ethyl-1-hexanol showed an increased concentration in the headspace of cells undergoing oxidative stress in untargeted analysis (p=0.00014). None of the VOCs that were linked to oxidative stress showed a significant correlation withFIO2(Rsrange: −0.015 to −0.065) or discriminated between patients withFIO2≥0.6 or below (area under the curve range: 0.48 to 0.55).ConclusionDespite a comprehensive translational approach, validation of known and novel volatile biomarkers of oxidative stress was not possible in patients at risk of pulmonary oxidative injury. The inconsistencies observed highlight the difficulties faced in VOC biomarker validation, and that caution is warranted in the interpretation of the pathophysiological origin of discovered exhaled breath biomarkers.
Exogenous 8-hydroxydeoxyguanosine attenuates doxorubicin-induced cardiotoxicity by decreasing pyroptosis in H9c2 cardiomyocytes
Authors: Hwang Soyoung , Kim Se-Hee , Yoo Kwai Han , Chung Myung-Hee , Lee Jin Woo , Son Kuk Hui 
Published: December 2022

AbstractDoxorubicin (DOX), which is widely used in cancer treatment, can induce cardiomyopathy. One of the main mechanisms whereby DOX induces cardiotoxicity involves pyroptosis through the NLR family pyrin domain containing 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Increased NAPDH oxidase (NOX) and oxidative stress trigger pyroptosis. Exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases reactive oxygen species (ROS) production by inactivating NOX. Here, we examined whether 8-OHdG treatment can attenuate DOX-induced pyroptosis in H9c2 cardiomyocytes. Exposure to DOX increased the peroxidative glutathione redox status and NOX1/2/4, toll-like receptor (TLR)2/4, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while an additional 8-OHdG treatment attenuated these effects. Furthermore, DOX induced higher expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a c-terminal caspase recruitment domain (ASC), and pro-caspase-1. Moreover, it increased caspase-1 activity, a marker of pyroptosis, and interleukin (IL)-1β expression. All these effects were attenuated by 8-OHdG treatment. In addition, the expression of the cardiotoxicity markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased by DOX, whereas the increase of ANP and BNP induced by DOX treatment was reversed by 8-OHdG. In conclusion, exogenous 8-OHdG attenuated DOX-induced pyroptosis by decreasing the expression of NOX1/2/3, TLR2/4, and NF-κB. Thus, 8-OHdG may attenuate DOX-induced cardiotoxicity through the inhibition of pyroptosis.
Initial treatment is associated with improved survival and end-of-life outcomes for patients with pancreatic cancer: a cohort study
Authors: Khan Rishad , Salim Misbah , Tanuseputro Peter , Hsu Amy T. , Coburn Natalie , Hallet Julie , Talarico Robert , James Paul D. 
Published: December 2022

Abstract
Background
We describe the association between initial treatment and end-of-life (EOL) outcomes among patients with pancreatic ductal adenocarcinoma (PDAC).

Methods
This population-based cohort study included patients with PDAC who died from April 2010–December 2017 in Ontario, Canada using administrative databases. We used multivariable models to explore the association between index cancer treatment (no cancer-directed therapy, radiation, chemotherapy, surgery alone, and surgery and chemotherapy), and primary (mortality, healthcare encounters and palliative care) and secondary outcomes (location of death, hospitalizations, and receipt of chemotherapy within the last 30 days of life).

Results
In our cohort (N = 9950), 56% received no cancer-directed therapy, 5% underwent radiation, 27% underwent chemotherapy, 7% underwent surgery alone, and 6% underwent surgery and chemotherapy. Compared to no cancer-directed therapy, radiation therapy (HR = 0.63), chemotherapy (HR = 0.43) surgery alone (HR = 0.32), and surgery and chemotherapy (HR = 0.23) were all associated with decreased mortality. Radiation (AMD = − 3.64), chemotherapy (AMD = -6.35), surgery alone (AMD = -6.91), and surgery and chemotherapy (AMD = -6.74) were all associated with fewer healthcare encounters per 30 days in the last 6 months of life. Chemotherapy (AMD = -1.57), surgery alone (AMD = -1.65), and surgery and chemotherapy (AMD = -1.67) were associated with fewer palliative care visits (all p-values for estimates above < 0.05). Treatment groups were associated with lower odds of institutional death and hospitalization at EOL, and higher odds of chemotherapy at EOL.

Conclusions
Receiving cancer-directed therapies was associated with higher survival, fewer healthcare visits, lower odds of dying in an institution and hospitalization at EOL, fewer palliative care visits, and higher odds of receiving chemotherapy at EOL.