bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II study protocol to assess safety and efficacy of adoptive cell therapy with anti-PD-1 plus low-dose pegylated-interferon-alpha in patients with metastatic melanoma refractory to standard of care treatments: the ACTME trial
Authors: van der Kooij Monique K , Verdegaal Els M E , Visser Marten , de Bruin Linda , van der Minne Caroline E , Meij Pauline M , Roozen Inge C F M , Jonker Mare A , van den Bosch Shelley , Liefers Gerrit-Jan , Speetjens Frank M , van der Burg Sjoerd H , Kapiteijn Ellen 
Published: April 2023

IntroductionTreatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.Methods and analysisPatients are treated in two phases. In phase I, the safety of the combination TIL and anti-PD-1 is assessed (cohort 1) according to CTCAE 4.03 criteria. Subsequently, the safety of cotreatment with PEG-IFNa is tested in cohort 2. The efficacy will be evaluated in the second phase of the trial. Efficacy is evaluated according to RECIST 1.1 and immune-related response criteria. Clinical and immunological parameters will be evaluated for their relation with clinical responsiveness.Ethics and disseminationEthical approval of the trial was obtained from the Central Committee on Research Involving Human Subjects in the Netherlands. The trial results will be shared with the scientific community at (inter)national conferences and by publication in a peer-reviewed journal.Trial registration numberNCT03638375.
Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population
Authors: Tannous Jonika , Pan Alan P , Potter Thomas , Bako Abdulaziz T , Dlouhy Katharine , Drews Ashley , Sostman Henry Dirk , Vahidy Farhaan S 
Published: April 2023

ObjectivesWe evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAbs) against postacute sequelae of SARS-CoV-2 infection (PASC).Design and settingA retrospective cohort study using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an eight-hospital tertiary hospital system in the Houston metropolitan area. Analyses were replicated across a global research network database.ParticipantsWe identified adult (≥18) patients with PASC. PASC was defined as experiencing constitutional (palpitations, malaise/fatigue, headache) or systemic (sleep disorder, shortness of breath, mood/anxiety disorders, cough and cognitive impairment) symptoms beyond the 28-day postinfection period.Statistical analysisWe fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted ORs with 95% CIs.ResultsPrimary analyses included 53 239 subjects (54.9% female), of whom 5929, 11.1% (95% CI 10.9% to 11.4%), experienced PASC. Both vaccinated breakthrough cases (vs unvaccinated) and mAb-treated patients (vs untreated) had lower likelihoods for developing PASC, aOR (95% CI): 0.58 (0.52–0.66), and 0.77 (0.69–0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared with mAb treatment. Replication analysis found identical frequency of PASC (11.2%, 95% CI 11.1 to 11.3) and similar protective effects against PASC for the COVID-19 vaccine: 0.25 (0.21–0.30) and mAb treatment: 0.62 (0.59–0.66).ConclusionAlthough both COVID-19 vaccines and mAbs decreased the likelihood of PASC, vaccination remains the most effective tool for the prevention of long-term consequences of COVID-19.
Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study
Authors: Royston Léna , Isnard Stéphane , Berini Carolina A. , Bu Simeng , Lakatos Peter L. , Bessissow Talat , Chomont Nicolas , Klein Marina , Lebouché Bertrand , de Pokomandy Alexandra , Kronfli Nadine , Costiniuk Cecilia T. , Thomas Rejean , Tremblay Cécile , Boivin Guy , Routy Jean-Pierre 
Published: April 2023

IntroductionChronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres correlated with gut permeability in PLWH on antiretroviral therapy (ART), which was associated with microbial translocation, systemic inflammation and non-infectious/non-AIDS comorbidities. Letermovir, a novel anti-CMV drug with a good safety profile, was recently approved for anti-CMV prophylaxis in allogeneic haematopoietic stem cell transplant recipients. A drastic and selective reduction of both low-grade replication and clinically significant CMV infections, combined with an improved immune reconstitution have been reported.In vitro, letermovir prevented CMV-induced epithelial disruption in intestinal tissues. Based on these findings, we aim to assess whether letermovir could inhibit CMV subclinical replication in CMV-seropositive PLWH receiving ART and, in turn, decrease CMV-associated gut damage and inflammation.Method and analysisWe will conduct a multi-centre, open-label, randomised, controlled clinical trial, including a total of 60 CMV-seropositive ART-treated PLWH for at least 3 years, with a viral load <50 copies/mL and CD4+count >400 cells/µL. Forty participants will be randomised to receive letermovir for 14 weeks and 20 participants will receive standard of care (ART) alone. Plasma, pheripheral blood mononuclear cells (PBMCs), and stool samples will be collected. Colon biopsies will be collected in an optional substudy. We will assess the effect of letermovir on gut damage, microbial translocation, inflammation and HIV reservoir size.Ethics and disseminationThe study was approved by Health Canada and the Research Ethics Boards of the McGill University Health Centre (MUHC-REB, protocol number: MP37-2022-8295). Results will be made available through publications in open access peer-reviewed journals and through the CIHR/CTN website.Trial registration numberNCT05362916.
Wireless physical activity monitor use among adults living with HIV in a community-based exercise intervention study: a quantitative, longitudinal, observational study
Authors: Turner Joshua R , Chow Judy , Cheng Justin , Hassanali Farhanna , Sevigny Hayley , Sperduti Michael , Chan Carusone Soo , Dagenais Matthieu , O'Brien Kelly K 
Published: April 2023

ObjectivesOur aim was to examine wireless physical activity monitor (WPAM) use and its associations with contextual factors (age, highest education level, social support and mental health) among adults living with HIV engaged in a community-based exercise (CBE) intervention.DesignQuantitative, longitudinal, observational study.SettingToronto YMCA, Ontario, Canada.ParticipantsEighty adults living with HIV who initiated the CBE intervention.InterventionParticipants received a WPAM to track physical activity during a 25-week CBE intervention involving thrice-weekly exercise, supervised weekly (phase 1) and a 32-week follow-up involving thrice-weekly exercise with no supervision (phase 2), completed in December 2018.Outcome measuresUptake was measured as participants who consented to WPAM use at initation of the intervention. Usage was defined as the proportion of days each participant had greater than 0 steps out of the total number of days in the study. We measured contextual factors using a baseline demographic questionnaire (age, highest education level), and median scores from the bimonthly administered Medical Outcomes Study-Social Support Scale and Patient Health Questionnaire (mental health), where higher scores indicated greater social support and mental health concerns, respectively. We calculated Spearman correlations between WPAM usage and contextual factors.ResultsSeventy-six of 80 participants (95%) consented to WPAM use. In phase 1, 66% of participants (n=76) and in phase 2, 61% of participants (n=64) used the WPAM at least 1 day. In phase 1, median WPAM usage was 50% (25th, 75th percentile: 0%, 87%; n=76) of days enrolled and in phase 2, 23% (0%, 76%; n=64) of days. Correlation coefficients with WPAM usage ranged from weak for age (ρ=0.26) and mental health scores (ρ=−0.25) to no correlation (highest education level, social support).ConclusionsMost adults living with HIV consented to WPAM use, however, usage declined over time from phase 1 to phase 2. Future implementation of WPAMs should consider factors to promote sustained usage by adults living with HIV.Trial registration numberNCT02794415.
Usability of exergames as a home-based balance training tool for older adults: protocol for a systematic review
Authors: Medeiros Candice Simões Pimenta de , Santos Jaiana Xavier , Restrepo Daniela Ramirez , Araújo Farias Luanna Barbara , Pacheco Thaiana Barbosa Ferreira , Cavalcanti Fabrícia Azevêdo da Costa 
Published: April 2023

IntroductionExergames are used in the clinical practice of geriatric rehabilitation to increase physical activity levels and motivate players/patients. Their use in the home environment makes it possible to perform fun, engaging and interactive training with a large number of repetitions, thereby reducing the negative repercussions of postural imbalance in older adults. The aim of this systematic review is to collate and analyse evidence on the usability of exergames as a tool for home-based balance training for older adults.Methods and analysisWe will include randomised controlled trials involving healthy older adults (aged 60 years or older) who are described as having impaired static or dynamic balance using any subjective or objective assessment criteria. We will search Web of Science, MEDLINE, Embase, Scopus, ScienceDirect and the Cochrane Library from database inception to December 2022. ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and ReBEC will be searched for ongoing or unpublished trials. Two independent reviewers will screen the studies and extract the data. The findings will be presented in the text and tables, and if possible, relevant meta-analyses will be performed. The risk of bias and the quality of evidence will be assessed based on the recommendations of the Cochrane Handbook and Grading of Recommendations, Assessment, Development and Evaluation, respectively.Ethics and disseminationEthical approval was not required because of the nature of this study. Findings will be disseminated through peer-reviewed publications, conference presentations and through clinical rehabilitation networks.PROSPERO registration numberCRD42022343290.
Incidence and predictors of acquired resistance to second-line antituberculosis drugs during the course of multi-drug resistant tuberculosis treatment: protocol for a systematic review and meta-analysis
Authors: Alemu Ayinalem , Bitew Zebenay Workneh , Diriba Getu , Gashu Emebet , Seid Getachew , Eshetu Kirubel , Kebede Abebaw , Gumi Balako 
Published: April 2023

IntroductionTo date, acquired resistance to second-line antituberculosis drugs (SLDs) during multi-drug resistant tuberculosis (MDR-TB) treatment is becoming a public health concern. Different studies have assessed the incidence of acquired resistance to SLDs. However, the findings are inconsistent and there is limited global evidence. Thus, we are going to assess the incidence and predictors of acquired resistance to SLDs during MDR-TB treatment.Methods and analysisWe designed this protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Electronic databases and grey literature sources will be searched systematically for articles published up to 25 March 2023. Studies reporting the incidence and predictors of acquired resistance to SLDs in MDR-TB patients will be explored. The studies will be managed using Endnote X8 citation manager and a stepwise approach will be followed to select studies. Data will be summarised using Microsoft Excel 2016 spreadsheet. A Newcastle-Ottawa Scale quality assessment and cochrane risk-of-bias tools will be used to assess the study’s quality. The authors will independently search databases, select studies, assess the study’s quality and extract data. Data will be analysed using STATA V.17 software. We will estimate the pooled incidence of acquired resistance with 95% CI. In addition, the pooled effect measures (OR, HR, risk ratio) with their 95% CI will be estimated. Heterogeneity will be assessed using the I2statistics. Publication bias will be assessed using funnel plot and Egger’s test. A subgroup analysis will be conducted for the primary outcome (acquired resistance) per each study characteristics such as WHO regional category, country’s TB/MDR-TB burden, data collection period and per the specific second-line anti-TB drug.Ethics and disseminationSince this study will be based on data extraction from published studies, ethical approval is not mandatory. The study will be published in peer-reviewed scientific journals and the findings will be presented at different scientific conferences.PROSPERO registration numberCRD42022371014.
Infection-related hospitalisation in young adults with systemic lupus erythematosus: data from the National Inpatient Sample
Authors: Dhital Rashmi , Guma Monica , Poudel Dilli R , Chambers Christina , Kalunian Kenneth 
Published: April 2023

IntroductionCare of young adults with SLE (YA-SLE, 18–24 years) is challenging due to major life transitions co-occurring with chronic healthcare needs. Studies have demonstrated poorer outcomes in the post-transition period. Epidemiological studies focused on serious infection-related hospitalisation (SIH) in YA-SLE are lacking.MethodsWe used National Inpatient Sample from 2010 to 2019 to study the epidemiology and outcomes of SIH for five common infections in SLE, namely sepsis, pneumonia, urinary tract infections, skin and soft tissue infections, and opportunistic infections. For time trends, we extended the dataset to cover 2000–2019. The primary outcome was the rate of SIH in YA-SLE compared with adults (25–44 years) with SLE and with young adults without SLE (YA-no SLE).ResultsFrom 2010 to 2019, we identified 1 720 883 hospital admissions with SLE in patients aged ≥18 years. Rates of SIH were similar in young adults and adults with SLE (15.0% vs 14.5%, p=0.12), but considerably higher than in the YA-no SLE group (4.2%, p<0.001). Among SLE with SIH, sepsis followed by pneumonia was the most common diagnosis. Significantly higher proportions of SIH among young adults than adults with SLE were comprised of non-white patients, belonged to the lowest income quartile and had Medicaid. However, only race/ethnicity was associated with SIH among YA-SLE. There was a higher prevalence of comorbid lupus nephritis and pleuritis among young adults compared with adults with SLE and SIH, and both comorbidities were associated with SIH in YA-SLE. Increasing rates of SIH, driven by sepsis, were seen over time.DiscussionYA- SLE had similar rates of SIH to adults with SLE. While hospitalised YA-SLE differed sociodemographically from SLE adults and YA-no SLE, only race/ethnicity was associated with SIH in the YA-SLE group. Lupus nephritis and pleuritis were associated with higher SIH in YA-SLE. Among SLE with SIH, increasing trends of sepsis deserve further study.
Synthesis and properties of 5,10-calixphyrin and its palladium-inserted complex
Authors: Kang Zhengxin , Wang Long , Li Zhongxin , Wu Qinghua , Wei Ying , Zuo Huiquan , Hao Erhong , Jiao Lijuan 
Published: April 2023

The reaction of dipyrrolomethane and acetone in the presence of acid and oxidant affords a mixture of 5,15-calixphyrin and 5,10-calixphyrin. The 5,10-calixphyrin readily forms an organometallic Pd(II) complex in 84% yield when treated with Pd(OAc)2 in acetonitrile at reflux. The crystal structure revealed that the 5,10-calixphyrin macrocycle adopted a twisted conformation because of the existence of two sp3-hybridized meso-carbon atoms, which was an impediment in [Formula: see text]-delocalization throughout the macrocycle core. The optimized palladium complex displayed a tetrahedron geometry with reduced distortion throughout the macrocycle. The introduction of palladium metal to the parent calixphyrin scaffold was found to have profound effects on the photophysical and electrochemical properties. Significantly, palladium-inserted 5,10-calixphyrin complex exhibits favorable absorption bands in the visible-near-infrared region with a maximum peak at 672 nm, which is a 148 nm red-shift as compared with that of free base 5,10-calixphyrin. The Pd(II) complex exhibits two reversible reductions and two irreversible oxidations and is more electron-deficient than the corresponding free-base 5,10-calixphyrin. Time-dependent density functional theory studies supported the experimental observations.
Abstract 1220: Carcinogenic nickel(II) is a replication stressor causing genotoxicity via DNA incorporation of rNMPs
Authors: Krawic Casey , Valiente Sophia , Zhitkovich Anatoly 
Published: April 2023

Abstract
Nickel(II) is a long-established inhalation carcinogen that causes lung and nasal tumors in humans and rodents. Despite its being a complete carcinogen, Ni(II) is DNA-unreactive and tested negative in the standard mutagenicity assays and consequently, is described as nongenotoxic. However, we have recently found that Ni(II) caused activation of the genotoxic stress-sensitive transcription factor p53, suggesting that this metal may possess some atypical, poorly detectable form(s) of genotoxicity. To determine what genotoxic or other cellular injury by Ni(II) upregulated p53, we examined multiple DNA damage responses and the role of several stress-sensitive kinases. We found that Ni(II)-induced phosphorylation and stabilization of p53 was mediated by ATR kinase but in its absence, by ATM kinase. Phosphorylation of p53 and CHK1 (another ATR target) occurred specifically in S phase, as determined by immunofluorescence and using synchronized cell populations. Inhibition of ATR strongly increased severity of replication stress and triggered activation of ATM kinase. Replication stress by Ni(II) was found to result from depletion of ribonucleotide reductase subunits through their higher turnover. We developed a novel fluorescent assay for detection of DNA-embedded rNMPs and found that Ni(II) induced a large increase in the DNA burden of ribonucleotides. The biological significance of DNA-incorporated rNMPs in Ni(II)-induced genotoxic responses was confirmed by the hypersensitivity of cells with inactivated ribonucleotide excision repair (RNAse H2 knockdown). Thus, our findings identified carcinogenic Ni(II) as a replication stressor inducing DNA incorporation of genotoxic rNMPs which are poorly detectable in the standard mutagenicity tests. Other protein-reactive carcinogen may also engage similar genotoxicity mechanisms.
Citation Format: Casey Krawic, Sophia Valiente, Anatoly Zhitkovich. Carcinogenic nickel(II) is a replication stressor causing genotoxicity via DNA incorporation of rNMPs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1220.
Abstract 1224: Quaking overexpression downregulates epithelial-mesenchymal transition in lung cancer cells
Authors: Kao Ying-Shiun , Hung Jung-Jyh 
Published: April 2023

Abstract
Background: Lung cancer is the leading cause of cancer death worldwide. Tumor recurrence is the most common cause of treatment failure after surgical resection. Quaking (QKI) is a functional protein that mediate alternative splicing, which belongs to the STAR family of the KH domain, containing RNA binding proteins. QKI regulate various genes via alternative splicing and circRNA formation during epithelial-mesenchymal transition (EMT). QKI takes an important part in tumorigenesis. QKI has been reported to be associated with progression of human cancer. However, several studies have indicated that QKI was associated with repression of EMT. Furthermore, the prognostic value of QKI in lung cancer patients and its regulatory mechanisms in EMT in lung cancer cells remains unknown.
Materials and Methods: A total of 79 patients with resected lung adenocarcinoma were included in the study. QKI expression was determined by immunohistochemistry in tumor specimens. The prognostic value of QKI overexpression and its relationship with clinicopathological variables were investigated. QKI knockdown was performed in H1299 and A549 cells. Western blotting analysis was performed to demonstrated QKI, E-cadherin and vimentin expression.
Results: QKI overexpression was significantly associated with female gender (P = 0.045). There was no significant association between QKI overexpression and predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.180). Univariate analysis indicated that predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.006) was a significant prognostic factor for worse recurrence-free survival (RFS). QKI overexpression (P = 0.042) was a significant prognostic factor for better RFS. Increased vimentin expression and decreased E-cadherin expression were identified in H1299 and A549 cells after QKI knockdown.
Conclusions: QKI overexpression has the potential to be a significant prognostic factor for better RFS in patients with resected lung adenocarcinoma. Increased vimentin expression and decreased E-cadherin expression were identified in H1299-QKIi cells. QKI may possess the ability to inhibit invasion and migration through repressing EMT.
Citation Format: Ying-Shiun Kao, Jung-Jyh Hung. Quaking overexpression downregulates epithelial-mesenchymal transition in lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1224.