Submission Date Research Articles

HIV Social-network intervention more effective in older populations in Kenya

US President’s Emergency Plan for HIV/AIDS has been credited with saving 25 million lives in sub-Sahara Africa and, as such, constitutes a preeminent US foreign policy achievement of the twenty-first century. However, the implementation of effective HIV/AIDS pharmacological interventions remains a challenge in rural Kenyan communities. Of particular importance are patient retention and care engagement and their interaction with age disparities that are sensitive to different socioeconomic contexts, as well as time-in-treatment. For the first time, we perform an intermediation and triple interaction intent-to-treat secondary analysis on a social network-based randomized controlled trial. We hypothesize that the temporal interactions of critical demographic features with a treatment/control indicator variable may significantly explain patient retention and that these results are intermediated by social network phenomena. We find that not only does extended time-in-treatment significantly improve primary outcomes, but the threefold interaction along with age and treatment itself is sufficiently flexible to fit the data remarkably well without unnecessary elaboration, an effect that is mediated via internalized stigma. This strongly suggests that patient retention varies by age group. Rather than deploying one-size-fits-all solutions, foreign and public policymakers should invest in research that considers how interventions might be optimized for different ages.Trial registration Clinical Trial Number. NCT02474992 (note: the main trial report was published here https://doi.org/10.1371/journal.pone.0255945.) Date of submission: June 6, 2015.

Call for papers 2025: JOVACET, Volume 8, Issue 1

You are invited to submit an article for the eighth volume of JOVACET to be published in October/November 2025. JOVACET is an accredited publication with the Department of Higher Education and Training. Articles should be topical with regard to current debates/discourses and recent research in the TVET, Adult, and Continuing Education and Training domains. Submissions should be of high quality and follow academic research/writing conventions of journal articles in the social sciences. Specifications can be found on the JOVACET website (www.jovacet.ac.za) or obtained from Dr Catherine Robertson at cathy@tcrobertson.co.za. Articles should comprise a maximum of 8 000 words, including the abstract of approximately 200 words and a list of references, and be submitted in MS Word format via the journal website at www.jovacet.ac.za or emailed to Dr Catherine Robertson at cathy@tcrobertson.co.za. Kindly follow the style guide which is provided on the website. We look forward to receiving your submissions! Due date for full paper submissions: 31 March 2025.

Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients

BACKGROUND The interactive media–based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated. METHODS This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States. Each site was provided with templated materials that had been reviewed and approved by a central institutional review board (cIRB). We collected the dates of milestones, including the study “kickoff call,” start of the social media campaign, dates of online community meetings, date of submission of site report to the cIRB, and cIRB approval date. RESULTS Sixty-two sites were cIRB approved at the time of this analysis. The median time from the kickoff call to the start of the social media campaign was 79 days, with an interquartile range of 33 to 126 days (range, 0–285 days). All social media campaigns ran for the prescribed period of at least 2 months. All sites conducted at least four online community meetings. The median number of days from the kickoff call to cIRB approval was 216 days (interquartile range, 168–281 days; range, 116–459 days). There was no significant difference between sites that had previous experience of EFIC trials. CONCLUSION Using the interactive media–based approach, CC/PD can be completed quickly; however, there are barriers that can incur substantial delays. Greater harmonization of local administrative processes would shorten the time to conduct CC/PD activities and facilitate the timely commencement and execution of EFIC trials. LEVEL OF EVIDENCE Systematic Review without Meta-analysis; Level III.

Conflicts of Interest in Bronchoscopy Research - Is Self-Reporting Sufficient?

Robotic assisted bronchoscopy has been enthusiastically adopted in the U.S. and transformed the management of patients with indeterminate pulmonary nodules. Unprecedented industry investments in research, development, and marketing have profoundly affected the bronchoscopy landscape, leading to concerns that conflicts of interest could influence the validity of bronchoscopy studies. Disclosures of conflicts of interest in research are predicated on open and transparent self-reporting. Are self-reported relevant conflicts of interest in articles pertaining to robotic assisted bronchoscopy accurate when compared to publicly available payments on the Centers of Medicare & Medicaid Services' Open Payments Database? All articles pertaining to robotic assisted bronchoscopy indexed on PubMed between 2016 and 2022 were screened for relevance. Articles appearing in the five journals with the most relevant publications were selected. General, research, and associated research payments reported in the Open Payments Database were recorded for each US physician-author with available data. "Relevant payments" refer to transactions made to authors by bronchoscopy-related companies. Documentation of all payments involving these companies during the three years prior to an article's submission date was obtained. These payments were compared to the self-reported conflicts of interest for each author, per article, and the number and value of payments were categorized and totaled. Twenty-seven articles were included, accounting for 75 U.S. physicians with data reported in the Open Payments Database. Of the $17 million in relevant payments reported, $9.9 million were not disclosed (57%). Sixty-eight of 75 (91%) of authors had incomplete physician disclosures. Excluding food and beverage payments, sixty authors had incomplete disclosures (80%). Relevant conflicts of interest appear to be inconsistently disclosed in publications on robotic assisted bronchoscopy, suggesting self-reporting may be an insufficient strategy. A centralized disclosure process that is automated or easier to use should be considered.

ANALISIS FAKTOR-FAKTOR YANG MENGHAMBAT KAJI ETIK PROTOKOL PENELITIAN: STUDI PADA KOMITE ETIK PENELITIAN FAKULTAS KEDOKTERAN UNIVERSITAS SEBELAS MARET, SURAKARTA

Ethics review is essential prior to conducting research involving humans and animals. This study aimed to evaluate the effectiveness of ethics review procedures and identify the causes of delayed ethical approval of the protocols submitted to Research Ethics Committee of the Faculty of Medicine, Universitas Sebelas Maret during 2022-2023. Retrospective data collected include protocol identity number, institution and educational level of the proposer, research type, date of protocol submission, completion of initial ethics review, and issuance of the ethical clearance certificate. A total of 458 protocols were received over 2 years period but the processing of 8 protocols were discontinued so that those 8 protocols were excluded from further analysis. Of the 450 protocols analysed, most involved human subjects (331; 73.6%). The majority of proposers were from UNS (309; 68.7%), were students (353; 78.4%), and had undergraduate education (166; 36.9%). The duration of the initial ethics review was generally <2 weeks (90.4%). Most (92.7%) protocols needed revision. The majority (66.4%) of proposers needed <2 weeks to revise the protocol. The total time for the entire ethics review process was 22.9 ± 14 days. Further evaluation found that the average duration needed for protocol revision was longer than that for reviewing (16 vs 9 days). It can be concluded that the ethics review process ran effectively so that almost all protocols submitted could undergo initial reviews in a relatively short time. The delayed ethical approval was due to the slow protocol revision process by the proposers.

An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma

Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2–4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2–4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36.

Retracted: Basic Concept of Healthy Aging

RETRACTION NOTICERetraction Notice (31th May 2024): The article by Hom Nath Chalise “Basic Concept of Healthy Aging” [JKAHS | Vol. 6 | No. 1 | Issue 16 | January - April 2023; https://doi.org/10.61814/jkahs.v6i1.763; published on 30 April 2023(submitted:14th December 2022) has been retracted from JKAHS by the editorial team for the duplicate publication on 31th May 2024.In response to the concern of duplicate publication of the article by a reader, the editorial team of JKAHS has reviewed the concern and has taken this decision of retracting the article.This article has been found to be already published in Journal of Patan Academy of Health Sciences (JPAHS) [Vol. 9 No. 3 (2022) https://doi.org/10.3126/jpahs.v9i3.52221] on 31 December 2022 (submitted: 29 May 2022) and in Asian Journal of Population Sciences (AJPS) [Vol. 2 (2023)https://doi.org/10.3126/ajps.v2i1.51096] on 10 January 2023 (submitted: 15 October 2022).As per the retraction policy of JKAHS, the author was contacted by the JKAHS EditorialTeam for an appropriate explanation. The author acknowledged that the article had been already under processing by Jat the time of submission to JKAHS. Based on the date of submission as well as publication on JPAHS, AJPS and JKAHS, the decision of retraction from JKAHS was made by the editorial meeting of JKAHS held on 31th May (Friday) 2024, and the need to correct the scientific record. JKAHS and AJPS were contacted from editorial office of JKAHS and make them aware of this retraction.Both of the involved journals have seen a copy of this retraction notice. The authors agree to this retraction notice.

Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups: ASCLEPIOS I/II Subgroup Analyses.

Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup. ASCLEPIOS I/II were identical, double-blind, double-dummy, active-controlled, multicenter, phase 3 trials. Participants were randomized (1:1) to receive ofatumumab 20 mg every 4 weeks or teriflunomide 14 mg once daily for up to 30 months. Pooled data were used to determine the efficacy/safety of ofatumumab vs teriflunomide in participants who self-identified as non-Hispanic Black, non-Hispanic Asian, Hispanic/Latino, or non-Hispanic White. Participants who did not self-identify into one of these groups were classified as other/unknown. Of the 1,882 participants, 64 (3.4%) self-identified as non-Hispanic Black, 71 (3.8%) as non-Hispanic Asian, 145 (7.7%) as Hispanic/Latino, and 1,538 (81.7%) as non-Hispanic White. Baseline participant demographics/characteristics were largely balanced across subgroups, aside from minor variations in sex, disease duration, and MRI lesions. From months 0 to 24, the proportion of ofatumumab vs teriflunomide-treated patients achieving NEDA-3 (odds ratio [95% CI]) was as follows: non-Hispanic Black, 33.3% vs 3.4% (15.9 [1.67-151.71; p = 0.0162]); non-Hispanic Asian, 42.9% vs 21.9% (3.18 [0.95-10.59; p = 0.06]); Hispanic/Latino, 36.6% vs 18.6% (3.21 [1.32-7.79; p = 0.01]); and non-Hispanic White, 37.4% vs 16.6% (3.57 [2.73-4.67; p < 0.0001]). Rates of AEs were generally similar between treatment groups and across race/ethnicity subgroups; no new or unexpected safety signals were identified. Ofatumumab was associated with greater proportions of NEDA-3 achievement than teriflunomide across race/ethnicity subgroups in the ASCLEPIOS trials. Within each treatment group, the proportion of patients achieving NEDA-3 from months 0 to 24 was similar across the subgroups and overall pooled population. Both ofatumumab and teriflunomide were well tolerated. Future MS trials should include ethnically diverse groups to better inform treatment decisions and improve real-world patient outcomes. ClinicalTrials.gov: NCT02792218 (clinicaltrials.gov/ct2/show/NCT02792218), NCT02792231 (clinicaltrials.gov/ct2/show/NCT02792231). Submission date: June 2, 2016. First enrollment: August 26, 2016. This study provides Class II evidence that among patients aged 18-55 years with RMS, the improvement in NEDA-3 with ofatumumab was comparably better than with teriflunomide among patients self-identified as non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, Hispanic/Latino, and other/unknown.

New Oncologic Drugs from 2008 to 2023-Differences in Approval and Access between the United States, Europe and Brazil.

Advancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008. Data were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Shapiro-Wilk, test and comparisons were made using the Mann-Whitney U test; the data are reported using median days and interquartile range (IQR1-IQR3). In total, 104 new oncologic drugs for the treatment of solid tumors were approved by the three agencies: 98 by the FDA, 90 by the EMA, and 68 by ANVISA. The cancer types with the highest number of first indications were lung cancer (n = 24), breast cancer (n = 15), and melanoma (n = 15). Most approvals were for oral medications (n = 63) and tyrosine-kinase inhibitors or other small-molecule inhibitors (n = 54). Time to approval after submission was as follows: the FDA-224 days (167-285); the EMA-364 days (330-418); and ANVISA-403 days (276-636) (p < 0.00001 for the FDA to the EMA and the FDA to ANVISA). The difference between submission dates among the agencies was as follows: EMA-FDA: 24 days (0-85); ANVISA-FDA: 255 (114-632); and ANVISA-EMA: 260 (109-645). The difference in approval dates between the agencies was as follows: EMA-FDA: 185 days (59-319); ANVISA-FDA: 558 (278-957); and ANVISA-EMA: 435 days (158-918). New oncologic drugs are submitted to the FDA and EMA for approval on similar dates; however, the longer appraisal period by the EMA pushes the approval date for Europe to approximately 6 months later. The same steps at ANVISA delay the approval by 1.5 years. Such procedures cause a significant difference in available medications between these regions.

Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150–300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized ‘responsive’ when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30–49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).

Towards Achieving Substantive Justice: The Importance of Extending the Time Limit for Resolving Presidential Election Disputes

Presidential election dispute resolution (PHPU) is complicated because its scope covers the entire territory of Indonesia and its application to Indonesian citizens in various parts of the world. The PHPU dispute resolution process must also guarantee maximum protection of constitutional rights. This research uses normative research methods using secondary data sources. This aims to assess the urgency of extending the deadline for resolving presidential election disputes, which is currently 14 working days from the date of submission. Research sculpture approach and conceptual approach. These findings illustrate the need for changes to legislation to extend the time limit for resolving PHPU disputes beyond the existing 14-day limit. In practice, this time period does not provide maximum opportunity for the presentation of evidence. Historical analysis shows that from the 2004 presidential election to 2024, not a single PHPU demand has been granted, mainly because the demand cannot be proven. The author emphasizes that a time limit that is too early does not guarantee substantive justice, which includes not only fair and accurate decision-making, so rational considerations are needed that produce rational and logical decisions and a process that allows each party to present their arguments comprehensively and obtain fair treatment in the judicial process.

A holistic lifestyle mobile health intervention for the prevention of type 2 diabetes and common mental disorders in Asian women with a history of gestational diabetes: a randomised control trial with 3-year follow-up protocol

BackgroundWomen with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4–6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore.MethodsThe study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child’s socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the “LVL UP App”, a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily “Life Hacks” (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the “HAPPY App”, a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period.DiscussionHigh rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs.Trial statusThe protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023.Trial registrationClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023.

Patient-Reported Outcomes in COVID-19 Treatment with Monoclonal Antibodies Reveal Benefits in Return to Usual Activities.

This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life. We analyzed patient-reported outcomes data from symptomatic outpatients in a phase1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active. In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2consecutive days: 14 vs 17days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17vs 21days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12vs 15days [nominal p = 0.0001] and 9 vs 11days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18days [nominal p = 0.0003] and 10 vs 13days [nominal p = 0.0041], respectively). mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs. GOV: Registration number, NCT04425629; Submission date June 11, 2020.

Recurrent Hydatid Disease of Temporal Bone and Skull Base: A Case Report and Literature Review.

Hydatid disease is a parasitic infestation caused by Echinococcus granulosus. The disease is rare in the head and neck region with varying presentations. We present a rare case of recurrent hydatid disease of the temporal bone with intracranial involvement; and the treatment thereof. Hydatid disease is endemic in few parts of the world, its occurrence in head and neck region is very rare. The commonest causative organism is E. granulosus giving rise to cystic hydatid disease. Most of the former are asymptomatic, but can give rise to symptoms because of their mass effects or rupture. Our case is a 38year male presenting to ENT department with recurrent left ear discharge, giddiness, headache and facial palsy having operated elsewhere twice in the past. The patient was investigated by Computed Tomography (CT) scanning and Magnetic Resonance Imaging (MRI) of temporal bones, head and neck regions. Which showed soft tissue attenuation of middle ear cleft and multiple cystic lesions in the middle and posterior cranial fossae indicating intracranial extension of disease. We operated for left subtotal petrosectomy with vestibular labyrinthectomy. During the perioperative period he was treated with Albendazole. Patient remains clinically and radiologically asymptomatic (post surgery 1year) till date of this manuscript submission. Hence, we report the recurrent hydatid cyst in the temporal bone and skull base, which was managed by combination of surgical and medical treatment.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Competition Time

Now that Surgo is linked to a Creative Commons license AND articles are regarded ascitable publications, we want to give students the opportunity to share their researchprojects with the world. In each issue we want to publish five student visual abstracts. What is a visual abstract? A visual abstract is a novel way of presenting research. It is a small graphic that gives abrief overview of the research question, methods and conclusions of the project. Inessence it is an eye catching summary of the research you have carried out. Below is anexample published by the BMJ(1):What do I need to submit? The first five visual abstracts that aresubmitted to surgo_uofg@yahoo.comby 10th February will receive £20.Thereafter, the five best visualabstracts that are submitted (asjudged by Prof. Cindy Chew) will beselected and displayed in eachsubsequent future issue. The authorsof these visual abstracts will alsoreceive £20 each. To wrap up this academic year ofSurgo, Prof. Matthew Walters haskindly offered to judge and decide onthe best visual abstract submittedover the course of the next twoissues. The winner will receive £100prize money. Your written abstract (introduction, methods, results, conclusion (250 words))Your visual abstract The name of one project supervisor The date of submission to the competition Good luck!

Retracted] Knockdown of SNHG16 suppresses the proliferation and induces the apoptosis of leukemia cells via miR‑193a‑5p/CDK8.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 7A on p. 1183 were strikingly similar to data appearing in different form in the following article written by different authors at different research institutes that had already been published prior to its date of submission: Lou L, Chen G, Zhong B and Liu F: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down‑regulation of PI3K/AKT signaling pathway. Biosci Rep 39: BSR20191182, 2019. In addition, possible anomalies were noted regarding the appearance of the western blots in the paper. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 1175‑1185, 2020; DOI: 10.3892/ijmm.2020.4671].

Post-market study requirements and associations with timely submission and regulatory action for oncology drugs receiving accelerated approval, 2011-2023.

11028 Background: For oncology drugs receiving accelerated approval (AA), the Food and Drug Administration (FDA) enforces Postmarketing Requirements (PMRs) to verify clinical benefit prior to regular approval. Although previous work has characterized the rigor and timeliness of confirmatory studies, the association between specificity and scope of PMR statements and the timeliness of PMR submission and ultimate approval status is not well understood. Methods: We identified 161 oncology indications granted AA between January 2011 and July 2023 using FDA’s Cancer AA database. We linked indications to 181 corresponding PMR statements using the Drugs@FDA database. We analyzed PMR statement scope and specificity based on the presence or requirement of eight characteristics: target population, comparator (active or placebo-controlled), randomization, multicenter trial, blinding (double-blind or open-label), enrollment target, follow-up duration, and endpoints. We used chi-square and t-tests to analyze associations between PMR characteristics and two primary outcomes: indication approval status (regular vs. withdrawn) and PMR timeliness (on time vs. late). We defined “late” submissions as PMRs submitted or withdrawals occurring after an expected PMR Final Report submission date. Ongoing PMRs were excluded from the timeliness analysis unless expected dates occurred before August 2023. Results: Among 181PMR statements, 98% percent specified target population, 81% endpoint (44% overall survival), 63% use of randomization, 54% comparator (40% active; 14% placebo-controlled), 30% follow-up duration 26% enrollment targets, 24% multicenter trial, and 13% double-blinding (and 8% open-label). Among AAs converted to regular approval, 82% of PMRs were submitted on time vs. 24% on-time for withdrawn AAs (p=0.001). Regular approval PMRs were submitted 10.2 months ahead of expected dates, whereas withdrawn AAs were submitted 14.5 months behind expected dates (p&lt;0.001). Compared late PMR submissions, on-time PMR submissions had lower enrollment (400 vs. 665, p=0.01), less blinding (19% vs. 40%, p=0.03), more frequent use of a single trial for both AA and PMR (38% vs. 8%, p=0.001), and primary endpoints other than overall or progression-free survival (36% vs. 5%, p&lt;0.001). Compared to late PMR submissions, on-time PMR submissions more often followed PMR statements that specified follow-up duration (39% vs. 13%, p=0.006) and non-survival primary endpoints (30% vs. 8%, p=0.01). Conclusions: There is marked variability in the contents of PMR statements for oncology AA drugs. Several characteristics of PMRs – including smaller enrollment size, surrogate endpoints, and single trials for AA and PMR – are associated with timely submission. These findings inform the specificity and scope of future FDA PMRs for oncology AA indications.

ACcoding: A graph-based dataset for online judge programming

A well-designed educational programming dataset is a valuable asset for students and educators. Such a dataset enables students to improve their programming performances continuously, provides researchers with significant data sources to identify students’ learning behaviours and enhance the quality of programming education. Several existing datasets for programming education are either limited by a small number of participating students or a short span of learning records, bringing great challenges to investigate students’ learning patterns in programming. We present a graph-based large-scale dataset specialized in programming learning on Online Judge (OJ) platform. The dataset, named ACcoding, was built by a university teaching group. As of the submission date of the initial manuscript of this paper (May 6, 2022), the dataset contains 4,046,652 task-solving records submitted by 27,444 students on 4,559 programming tasks over a span of 6 years. The large size of the dataset, combined with rich functional features, empowers educators to trace students’ programming progress and choose appropriate programming tasks for specific training purposes. We also presents examples of applications used by the dataset.

Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice.MethodsInvestigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain.DiscussionData from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention.Trial registrationclinicaltrials.gov NCT05855109 (submission date: 3 May 2023).