bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Status of Human Papillomavirus–Targeted Therapies Development in Head and Neck Cancer
Authors: Park Jong Chul , Bertaux Brittany , Park Junseok , Park Seongwoo 
Published: June 2023

PURPOSEWhile the incidence of smoking-related head and neck squamous cell carcinoma (HNSCC) has been declining, that of human papillomavirus (HPV)–mediated HNSCC has rapidly increased in the past decades worldwide. Despite rapid advances in therapeutics for solid tumors with novel immunotherapy and targeted therapeutic agents, no breakthroughs have yet been made in the treatment of advanced HPV+ HNSCCs. This review aims to summarize the concepts and designs, early trial results, and future directions of various HPV-targeted experimental therapeutics for HPV+ HNSCC.MATERIALS AND METHODSGuided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, a systemic literature search of PubMed was conducted for HPV-targeted therapeutics using the following search terms: HPV, head and neck squamous cell carcinoma, and therapy. For clinical trial data, publications, major oncology conference abstracts, and the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov) information were reviewed. This review focused on the ones that are in the clinical stage and currently in active ongoing evaluation. The therapeutics not actively evaluated in HNSCC, in the preclinical stage, or terminated for further development were excluded.RESULTSDiverse approaches are being actively explored to target HPV+ HNSCC, including therapeutic vaccines of various modalities, HPV-specific immune cell–activating agents, and adaptive cellular therapeutics. All these novel agents use immune-based mechanisms and target constitutively expressed oncogenic HPV E6 and/or E7 viral proteins. Most therapeutics demonstrated excellent safety but single-agent activities are only modest. Many are being tested in combination with immune checkpoint inhibitors.CONCLUSIONOur review summarized various novel HPV-targeted therapeutics that are in the clinical phase for HPV+ HNSCC. Early-phase trial data suggest the feasibility and promising efficacy. Further strategies, including selecting the optimal combination and understanding and overcoming resistant mechanisms, are warranted for successful development.
Protective Effects of Imeglimin and Metformin Combination Therapy on β-Cells in db/db Male Mice
Authors: Nishiyama Kuniyuki , Ono Masato , Tsuno Takahiro , Inoue Ryota , Fukunaka Ayako , Okuyama Tomoko , Kyohara Mayu , Togashi Yu , Fukushima Setsuko , Atsumi Takuto , Sato Aoi , Tsurumoto Asuka , Sakai Chisato , Fujitani Yoshio , Terauchi Yasuo , Ito Shuichi , Shirakawa Jun 
Published: June 2023

Abstract
Imeglimin and metformin act in metabolic organs, including β-cells, via different mechanisms. In the present study, we investigated the impacts of imeglimin, metformin, or their combination (Imeg + Met) on β-cells, the liver, and adipose tissues in db/db mice. Imeglimin, metformin, or Imeg + Met treatment had no significant effects on glucose tolerance, insulin sensitivity, respiratory exchange ratio, or locomotor activity in db/db mice. The responsiveness of insulin secretion to glucose was recovered by Imeg + Met treatment. Furthermore, Imeg + Met treatment increased β-cell mass by enhancing β-cell proliferation and ameliorating β-cell apoptosis in db/db mice. Hepatic steatosis, the morphology of adipocytes, adiposity assessed by computed tomography, and the expression of genes related to glucose or lipid metabolism and inflammation in the liver and fat tissues showed no notable differences in db/db mice. Global gene expression analysis of isolated islets indicated that the genes related to regulation of cell population proliferation and negative regulation of cell death were enriched by Imeg + Met treatment in db/db islets. In vitro culture experiments confirmed the protective effects of Imeg + Met against β-cell apoptosis. The expression of Snai1, Tnfrsf18, Pdcd1, Mmp9, Ccr7, Egr3, and Cxcl12, some of which have been linked to apoptosis, in db/db islets was attenuated by Imeg + Met. Treatment of a β-cell line with Imeg + Met prevented apoptosis induced by hydrogen peroxide or palmitate. Thus, the combination of imeglimin and metformin is beneficial for the maintenance of β-cell mass in db/db mice, probably through direct action on β-cells, suggesting a potential strategy for protecting β-cells in the treatment of type 2 diabetes.
Parallels between oncogene-driven cardiac hyperplasia and heart regeneration in zebrafish
Authors: Pfefferli Catherine , Bonvin Marylène , Grepper Dogan , Robatel Steve , König Désirée , Lischer Heidi E. L. , Bruggmann Rémy , Jaźwińska Anna 
Published: June 2023

ABSTRACT
The human heart is poorly regenerative and cardiac tumors are extremely rare. Whether the adult zebrafish myocardium is responsive to oncogene overexpression and how this condition affects its intrinsic regenerative capacity remains unknown. Here, we have established a strategy of inducible and reversible expression of HRASG12V in zebrafish cardiomyocytes. This approach stimulated a hyperplastic cardiac enlargement within 16 days. The phenotype was suppressed by rapamycin-mediated inhibition of TOR signaling. As TOR signaling is also required for heart restoration after cryoinjury, we compared transcriptomes of hyperplastic and regenerating ventricles. Both conditions were associated with upregulation of cardiomyocyte dedifferentiation and proliferation factors, as well as with similar microenvironmental responses, such as deposition of nonfibrillar Collagen XII and recruitment of immune cells. Among the differentially expressed genes, many proteasome and cell-cycle regulators were upregulated only in oncogene-expressing hearts. Preconditioning of the heart with short-term oncogene expression accelerated cardiac regeneration after cryoinjury, revealing a beneficial synergism between both programs. Identification of the molecular bases underlying the interplay between detrimental hyperplasia and advantageous regeneration provides new insights into cardiac plasticity in adult zebrafish.
Ultra-Low Dose of Superparamagnetic Iron Oxide Nanoparticles for Sentinel Lymph Node Detection in Patients with Breast Cancer
Authors: Mirzaei Nushin , Wärnberg Fredrik , Zaar Pontus , Leonhardt Henrik , Olofsson Bagge Roger 
Published: June 2023

Abstract
Background
Sentinel lymph node (SLN) status is pivotal for treatment decision-making in patients with breast cancer. Superparamagnetic iron oxide nanoparticles (SPIO) have been shown to be equivalent to the dual technique with technetium99m (Tc99) and blue dye (BD) for SLN detection. The aim of this study was to determine the feasibility of detecting SLNs using an ultra-low dose of SPIO.

Method
Patients planned for breast conserving surgery and SLN biopsy were included. An intradermal injection of 0.1 mL SPIO was administered at the areolar border up to 7 days before surgery. Tc99/BD was administered according to clinical routine. SLNs were detected during surgery using a handheld magnetometer. All nodes with a magnetic and/or radioactive signal, as well as blue or clinically suspicious nodes, were harvested and analyzed.

Results
In 50 patients, SPIO was injected a median of 4 days before surgery. At least one SLN was found in all patients with both methods. A total of 98 SLNs were removed; 90 were detected using SPIO and 88 using Tc99/BD. Of the 90 SLNs detected by SPIO, 80 were Tc99/BD positive (concordance 89%). Histopathological analysis classified 16 patients with tumor cells deposit and 9 with macro-metastasis > 2mm, where one SLN was identified only by the radioactive technique and one only by the magnetic technique.

Discussion
SLN detection using 0.1 mL ultra-low dose SPIO injected intradermally was successful in all patients. A future analysis will determine whether the approach using an ultra-low dose of SPIO injected intradermally will minimize skin staining and MRI artefacts.
Customers as Friendly Shareholders: Uncovering the Complex Mutual Fund-Broker Relationship
Authors: Kumar Nitish , Tang Yuehua , Wei Kelsey D. 
Published: June 2023

This paper examines mutual funds’ dual role as both clients and shareholders of broker banks. Mutual funds are more likely to hold and significantly overweight stocks of their broker banks. In line with the portfolio decisions, fund voting is biased toward broker management in contentious proposals. Such voting bias is inconsistent with maximizing broker banks’ shareholder value yet significantly affects voting outcomes and the presence of contentious proposals at the banks’ shareholder meetings. Furthermore, we show that although client funds are rewarded with preferential initial public offering allocations from connected brokers for their voting support, fund managers’ engagement in reciprocal practices is ultimately determined by the economic tradeoffs they face. Our study not only uncovers a new mechanism—being brokers’ friendly shareholders—through which the two parties maintain their quid pro quo relationships but also raises a broader concern about governance of important financial institutions. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2023.4820 .
Educating nurses caring for paediatric inflammatory bowel disease patients receiving biologics: the impact of a virtual event
Authors: Gil-Zaragozano Elena , Williams Jo 
Published: June 2023

Background: A virtual educational and networking event took place for registered nurses caring for administering biologic therapy in paediatric Inflammatory Bowel Disease (IBD) patients and their families. The aim was to establish the level of self-reported competencies of the nurses and to evaluate the impact that the event had on them. Methods: Participants were requested to complete an online questionnaire before and after the interprofessional education event. Results: Some 21 pre–event questionnaires were completed. Of these, 81% (17) reported no previous relevant training, 20% (4) did not feel competent in the administration of biologics and patient monitoring and 29% (6) did not feel competent to meet the patient's holistic needs. A total of 13 post-event evaluations were completed. All (13) agreed/strongly agreed with feeling more competent in caring for patients and 84.7% (11) agreed/strongly agreed with feeling more competent in administering and monitoring the biologic therapy. A total of 77% (10) of participants could identify changes to their practice post-event. Conclusion: This study highlighted the need for interprofessional education for nurses caring for paediatric inflammatory bowel disease patients, particularly where care is delivered in district general hospitals. Feedback demonstrated that virtual educational events are effective in raising self-reported nursing competencies and in ensuring high standards of practice.
Major trauma presentations and patient outcomes in English hospitals during the COVID-19 pandemic: An observational cohort study
Authors: Marincowitz Carl , Bouamra Omar , Coats Tim , Surendra Kumar Dhushy , Lockey David , Mason Lyndon , Newcombe Virginia , Thompson Julian , Edwards Antoinette , Lecky Fiona 
Published: June 2023

BackgroundSingle-centre studies suggest that successive Coronavirus Disease 2019 (COVID-19)-related “lockdown” restrictions in England may have led to significant changes in the characteristics of major trauma patients. There is also evidence from other countries that diversion of intensive care capacity and other healthcare resources to treating patients with COVID-19 may have impacted on outcomes for major trauma patients. We aimed to assess the impact of the COVID-19 pandemic on the number, characteristics, care pathways, and outcomes of major trauma patients presenting to hospitals in England.Methods and findingsWe completed an observational cohort study and interrupted time series analysis including all patients eligible for inclusion in England in the national clinical audit for major trauma presenting between 1 January 2017 and 31 of August 2021 (354,202 patients). Demographic characteristics (age, sex, physiology, and injury severity) and clinical pathways of major trauma patients in the first lockdown (17,510 patients) and second lockdown (38,262 patients) were compared to pre-COVID-19 periods in 2018 to 2019 (comparator period 1: 22,243 patients; comparator period 2: 18,099 patients). Discontinuities in trends for weekly estimated excess survival rate were estimated when lockdown measures were introduced using segmented linear regression.The first lockdown had a larger associated reduction in numbers of major trauma patients (−4,733 (21%)) compared to the pre-COVID period than the second lockdown (−2,754 (6.7%)). The largest reductions observed were in numbers of people injured in road traffic collisions excepting cyclists where numbers increased. During the second lockdown, there were increases in the numbers of people injured aged 65 and over (665 (3%)) and 85 and over (828 (9.3%)).In the second week of March 2020, there was a reduction in level of major trauma excess survival rate (−1.71%; 95% CI: −2.76% to −0.66%) associated with the first lockdown. This was followed by a weekly trend of improving survival until the lifting of restrictions in July 2020 (0.25; 95% CI: 0.14 to 0.35). Limitations include eligibility criteria for inclusion to the audit and COVID status of patients not being recorded.ConclusionsThis national evaluation of the impact of COVID on major trauma presentations to English hospitals has observed important public health findings: The large reduction in overall numbers injured has been primarily driven by reductions in road traffic collisions, while numbers of older people injured at home increased over the second lockdown. Future research is needed to better understand the initial reduction in likelihood of survival after major trauma observed with the implementation of the first lockdown.
Pharmacokinetics, feasibility and safety of co-administering azithromycin, albendazole, and ivermectin during mass drug administration: A review
Authors: McPherson Scott , Solomon Anthony W. , Seife Fikre , Solomon Hiwot , Gebre Teshome , Mabey David C. W. , Marks Michael 
Published: June 2023

Introduction
Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration.

Methodology
We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1st, 1995 through October 1st, 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone.

Results
We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded.

Conclusion
There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes.
Seroprevalence of SARS-CoV-2 IgG and associated factors among people living with HIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso, a sub-Saharan African country
Authors: Kaboré Odilon D. , Poda Armel , Ouattara Cheick Ahmed , Michodigni Fernand N. , Belem Abdoul-Aziz , Sawadogo Yacouba , Zoungrana Jacques , Galal Lokman , Meda Clément Z. , Godreuil Sylvain , Ouédraogo Abdoul-Salam 
Published: June 2023

Objective
This study aimed to evaluate the seroprevalence of anti-SARS-CoV-2 IgG and factors associated with the infection among PLWHIV over the first 12 months following the outbreak of COVID-19 in Burkina Faso.

Design
A retrospective cross-sectional study of plasma samples collected from March 9, 2020, and March 8, 2021, at the outpatient HIV referral center, before the introduction of the SARS-CoV-2 vaccine in Burkina Faso.

Methods
Anti-SARS-CoV-2 IgG were detected in plasma using DS-ЕIA-ANTI-SARS-CoV-2-G (S) kit. Logistic regressions were used to compare SARS-CoV-2 specific immune responses between groups and within subgroups.

Results and discussion
A total of 419 plasma were subjected to serological diagnosis. None of the participants was vaccinated against COVID-19 during the period of sample collection, and 130 samples were positive for anti-SARS-CoV-2 IgG, giving a prevalence of 31.0% (95% CI 26.6–35.7). The median CD4 cell count was 661 cells/μL (IQR,422–928). Retailers had half the risk of being infected compared to housemaids with an OR of 0.49 (p = 0.028, 95% CI 0.26–0.91). Likewise, the risk of infection was 1.69 times higher in patients on integrase inhibitors compared to that of patients on non-nucleoside reverse transcriptase inhibitors (p = 0.020, 95% CI 1.09–2.63).

Conclusion
Our study reveals a high seroprevalence among PLWHIV to SARS-CoV-2 during the first year of the pandemic. In addition, PLWHIV on integrase inhibitors are 1.69 times more likely to be infected than PLWHIV on non-nucleoside inhibitors, and this observation remains an intriguing topic that still needs to be clarified.
Is movement variability altered in people with chronic non-specific low back pain? A systematic review
Authors: Alsubaie Amal M. , Mazaheri Masood , Martinez-Valdes Eduardo , Falla Deborah 
Published: June 2023

Background
Variability in spine kinematics is a common motor adaptation to pain, which has been measured in various ways. However, it remains unclear whether low back pain (LBP) is typically characterised by increased, decreased or unchanged kinematic variability. Therefore, the aim of this review was to synthesise the evidence on whether the amount and structure of spine kinematic variability is altered in people with chronic non-specific LBP (CNSLBP).

Methods
Electronic databases, grey literature, and key journals were searched from inception up to August 2022, following a published and registered protocol. Eligible studies must investigated kinematic variability in CNSLBP people (adults ≥18 years) while preforming repetitive functional tasks. Two reviewers conducted screening, data extraction, and quality assessment independently. Data synthesis was conducted per task type and individual results were presented quantitatively to provide a narrative synthesis. The overall strength of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation guidelines.

Findings
Fourteen observational studies were included in this review. To facilitate the interpretation of the results, the included studies were grouped into four categories according to the task preformed (i.e., repeated flexion and extension, lifting, gait, and sit to stand to sit task). The overall quality of evidence was rated as a very low, primarily due to the inclusion criteria that limited the review to observational studies. In addition, the use of heterogeneous metrics for analysis and varying effect sizes contributed to the downgrade of evidence to a very low level.

Interpretation
Individuals with chronic non-specific LBP exhibited altered motor adaptability, as evidenced by differences in kinematic movement variability during the performance of various repetitive functional tasks. However, the direction of the changes in movement variability was not consistent across studies.
LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting
Authors: Marincowitz Carl , Hodkinson Peter , McAlpine David , Fuller Gordon , Goodacre Steve , Bath Peter A. , Sbaffi Laura , Hasan Madina , Omer Yasein , Wallis Lee 
Published: June 2023

Background
Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.

Methods
Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.

Results
We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.

Conclusion
The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.