bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
Authors: Li Xuejie , Liu Zheqi , Zhou Wenkai , Liu Xiaofang , Cao Wei
Published: August 2021

Objective

Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear.

Materials and methods

Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations.

Results

In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC.

Conclusion

In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.
Experiences of COVID-19-related anti-Asian discrimination and affective reactions in a multiple race sample of U.S. young adults
Authors: Hahm Hyeouk Chris , Xavier Hall Casey D. , Garcia Kana Tsurudome , Cavallino Anna , Ha Yoonsook , Cozier Yvette C. , Liu Cindy
Published: August 2021

Background

Little remains known about both Asian and Asian American (A/AA) and non-Asian young adults’ experiences and affective reactions regarding COVID-19 anti-Asian discrimination. To our knowledge, this is the first study that explores the nature and impact of COVID-19 anti-Asian discrimination within a multi-racial sample.

Methods

This study uses qualitative open-ended responses from a sub-sample of Wave I of the COVID-19 Adult Resilience Experiences Study (CARES) data collected between March to September 2020. Thematic analysis was used to explore two open-ended questions: “Are there experiences we missed in the survey so far that you wish to describe?” and “What are your thoughts about the current social climate?” The data analysis for this study focused on 113 discrimination or racism-related comments.

Results

A total of 1331 young adults completed an online survey of which 611 provided comments; a multi-racial sample of 95 individuals (65.3% non-Asians, 24.7% A/AA) contributed 113 COVID-19 anti-Asian discrimination or racism-related comments. Two overarching themes were: types of discrimination (societal, interpersonal, intrapersonal) and affective reactions to discrimination (fear, anxiety/distress, hopelessness/depression, and avoidance). Not only did both A/AA and non-Asian participants report witnessing or hearing reports of anti-Asian discrimination, but both groups described having negative affective reactions to anti-Asian discrimination.

Conclusion

Anti-Asian discrimination in the face of COVID may be more widespread than initial reports indicate. Our finding suggests that anti-Asian discrimination is a societal illness that impacts all populations in the U.S. This calls for cross-racial coalitions and solidarity in the fight against discrimination and racism.
The effects of race/ethnicity and physician recommendation for physical activity on physical activity levels and arthritis symptoms among adults with arthritis
Authors: Huckleby Jeremy , Williams Faustine , Ramos Rose , Nápoles Anna María
Published: August 2021

Background

Among U.S. adults with physician-diagnosed arthritis, we examined the association of 1) participant race/ethnicity with meeting physical activity guidelines and arthritis symptoms, and 2) the association of receipt of a physician exercise recommendation with physical activity levels and arthritis symptoms, and whether race/ethnicity moderates these associations.

Methods

Retrospective, cross-sectional study of National Health Interview Survey pooled data from 2002, 2006, 2009, and 2014 from 27,887 U.S. adults aged ≥18 years with arthritis. Outcomes were meeting aerobic (yes/no) and strengthening guidelines (yes/no), arthritis-associated activity limitations (yes/no) and arthritis-related pain (0–10; higher score = more pain). Predictors were race/ethnicity (White, African American, Latino, and Asian) and receipt of physician recommendation for exercise (yes/no). Covariates included demographic and health characteristics.

Results

Adjusting for covariates, African Americans were more likely (AOR = 1.27; 95% CI 1.12, 1.43) and Asians were less likely (AOR = 0.75; 95% CI 0.61, 0.92) than Whites to meet muscle strengthening activity guidelines. Compared to Whites, African Americans (B = 0.48; 95% CI 0.24, 0.72) and Latinos (B = 0.44; 95% CI 0.15, 0.72) reported more severe, while Asians reported less severe (B = -0.68; 95% CI -1.22, − 0.14) joint pain. Controlling for covariates, physician exercise recommendation was associated with meeting aerobic (AOR = 1.20; 95% CI 1.11, 1.30) and strengthening (AOR = 1.21; 95% CI 1.11, 1.33) guidelines, regardless of race/ethnicity except for a weak negative association with meeting strengthening guidelines (AOR = 0.85; CI 0.74–0.99) among Latinos.

Conclusions

Disparities in pain exist for African Americans and Latinos with arthritis. Physician exercise recommendation is critical among patients with arthritis to relieve symptom burden.
Risk perception of COVID-19 among sub-Sahara Africans: a web-based comparative survey of local and diaspora residents
Authors: Abu Emmanuel Kwasi , Oloruntoba Richard , Osuagwu Uchechukwu Levi , Bhattarai Dipesh , Miner Chundung Asabe , Goson Piwuna Christopher , Langsi Raymond , Nwaeze Obinna , Chikasirimobi Timothy G. , Ovenseri-Ogbomo Godwin O. , Ekpenyong Bernadine N. , Charwe Deborah Donald , Mashige Khathutshelo Percy , Ishaya Tanko , Agho Kingsley Emwinyore
Published: August 2021

Background

Perceived risk towards the coronavirus pandemic is key to improved compliance with public health measures to reduce the infection rates. This study investigated how Sub-Saharan Africans (SSA) living in their respective countries and those in the diaspora perceive their risk of getting infected by the COVID-19 virus as well as the associated factors.

Methods

A web-based cross-sectional survey on 1969 participants aged 18 years and above (55.1% male) was conducted between April 27th and May 17th 2020, corresponding to the mandatory lockdown in most SSA countries. The dependent variable was the perception of risk for contracting COVID-19 scores. Independent variables included demographic characteristics, and COVID-19 related knowledge and attitude scores. Univariate and multiple linear regression analyses identified the factors associated with risk perception towards COVID-19.

Results

Among the respondents, majority were living in SSA (n = 1855, 92.8%) and 143 (7.2%) in the diaspora. There was no significant difference in the mean risk perception scores between the two groups (p = 0.117), however, those aged 18–28 years had lower risk perception scores (p = 0.003) than the older respondents, while those who were employed (p = 0.040) and had higher levels of education (p < 0.001) had significantly higher risk perception scores than other respondents. After adjusting for covariates, multivariable analyses revealed that SSA residents aged 39–48 years (adjusted coefficient, β = 0.06, 95% CI [0.01, 1.19]) and health care sector workers (β = 0.61, 95% CI [0.09, 1.14]) reported a higher perceived risk of COVID-19. Knowledge and attitude scores increased as perceived risk for COVID-19 increased for both SSAs in Africa (β = 1.19, 95% CI [1.05, 1.34] for knowledge; β = 0.63, 95% CI [0.58, 0.69] for attitude) and in Diaspora (β = 1.97, 95% CI [1.16, 2.41] for knowledge; β = 0.30, 95% CI [0.02, 0.58] for attitude).

Conclusions

There is a need to promote preventive measures focusing on increasing people’s knowledge about COVID-19 and encouraging positive attitudes towards the mitigation measures such as vaccines and education. Such interventions should target the younger population, less educated and non-healthcare workers.
Clinical experience with the treatment of retroperitoneal vascular leiomyosarcoma originating from large veins
Authors: Zhang Hong-xian , Wang Kai , Hong Peng , Lu Min , Liu Zhuo , Liu Lei , Wang Guo-liang , Ma Lu-lin
Published: August 2021

Background

Retroperitoneal vascular leiomyosarcoma (RVLMS) is an extremely rare disease in clinical practice, and it has poor prognosis. This article is to explore the diagnosis and treatment of RVLMS and present our experience.

Methods

Data of RVLMS patients were continuously collected in our hospital from August 2018 to February 2020: two males and two females with a median age of 56 (min–max = 33–61) years were included. Patients in whom paraganglioma could not be excluded were asked to take phenoxybenzamine before surgery. A multi-disciplinary team (MDT) meeting had been held and surgery was recommended. The operation procedures varied based on the tumor location, shape, and stage, and the core steps were "exposure of the retroperitoneum and tumor, identification of vital blood vessels, blocking the bloodstream, complete removal of the tumor and tumor thrombus, and release of blood flow". A Satinsky clamp was used to partially block the blood vessels. Follow-up was conveyed by revisits and phone calls.

Results

One patient underwent open surgery, and three patients underwent laparoscopic surgery, one of whom underwent conversion to open surgery. The procedures were finished successfully, with a median operative time of 314.5 (min–max = 224–467) mins. The median amount of intraoperative bleeding was 550 (min–max = 200–1500) ml, and three patients had transfusion during the operation. The mass was irregular in shape, with a median maximum size of 7.45 (min–max = 4.2–10.7) cm, and the pathological examination confirmed RVLMS, which has spindle-shape, high mitotic activity and atypia. One week after the operation, the median serum creatinine level was 85 (min–max = 70–99) µmol/L. The median follow-up time was 16 (min–max = 13–21) months, and 1 case reported asymptomatic recurrence.

Conclusion

Uncharacteristic manifestations and imaging features contribute to the problematic diagnosis of RVLMS. Comprehensive preoperative evaluation and careful surgical planning are essential. Multicenter research is needed in the future to reach a dominant consensus.
Evaluation of bactericidal effects of ultraviolet light C irradiation on cariogenic bacteria: An in vitro study
Authors: Alharbi Moayyad , Bakitian Fahad , Alenezi Ali
Published: August 2021

Backgrounds

Ultraviolet light C (UVL-C) irradiation has demonstrated an antimicrobial action against various pathogens. This study aimed to evaluate the bactericidal effect of UVL-C irradiation against cariogenic oral bacteria (Streptococcus mutans) in single layers and colonies grown on solid surfaces.

Methods

Two different experiments were performed. In the first experiment, a single layer of Streptococcus mutans bacteria on agar plates was exposed to UVL-C irradiation at energies from 0 to 21 mWs/cm2. The second experiment was conducted to inhibit viability of bacterial colonies on solid surfaces. The samples were derived from saliva from a patient where bacteria were grown on plastic strips and then exposed to UVL-C. The highest energy was 1050 mWs/cm2.

Results

Exposure to 21 mWs/cm2 was bactericidal in single layers of Streptococcus mutans. The result for bacterial colonies on solid surfaces indicated only a bacteriostatic effect, even at energies of 1050 mWs/cm2.

Conclusions

Ultraviolet light C exhibits bactericidal effects on single layers of Streptococcus mutans but has a limited effect on bacterial colonies in a biofilm. It is a matter of debate whether these in vitro results would have the same effect in clinical setting.
Efficacy of pedagogical framework in neonatal resuscitation skill learning in a resource-limited setting: a randomized controlled trial
Authors: Liaqat Mishal , Hussain Muhammad , Afzal Muhammad , Altaf Maryam , Khan Sadia , Gilani Syed Amir , Liaqat Iram
Published: August 2021

Background

The educational efficacy in neonatal resuscitation relies on the subject and teaching strategies. Therefore, it is imperative to test diverse educational methods if they are more instructive to engage students in active learning and practicing knowledge. Hence, the present study aims to investigate the efficacy of a pedagogical framework in neonatal resuscitation skill learning among nursing students in a resource-limited setting.

Methods

A single-blind randomized controlled trial was conducted between October 2020 to March 2021. Sixty nursing students in the 3rd and 4th year of professional training were randomly allocated to the pedagogy and the traditional group. The pedagogy group learned via 6-step LSPPDM (Learn, See, Practice, Prove, Do, Maintain) pedagogy including lectures, video, clinical observation, skill sessions under supervision, and self-directed practice. The traditional group learned through 2-step (Learn, Practice) method that included lectures and skill sessions under supervision. The outcomes measured included technical and non-technical skills in neonatal resuscitation. The technical skill deals with steps such as stimulation, ventilation, oxygenation, intubation, chest compression, medications, and reporting. Non-technical skills refer to teamwork skills that focus on the interaction between leader and helper. Both skills were measured through previously published validated tools two times before and after the intervention by blinded assessors in a simulated delivery room.

Results

Overall, the skill was significantly improved in both groups after intervention. Yet, the results showed that the mean difference of technical skill score in the pedagogy group (24.3 ± 3.5) was significantly higher (p <  0.001) compared to the traditional group (16.2 ± 2.4). Likewise, the mean difference of non-technical skill score in the pedagogy (36.9 ± 1.9) was highly significant (p <  0.001) compared to the traditional group (31.2 ± 1.7).

Conclusions

The LSPPDM pedagogy was found more effective in enhancing technical and non-technical skills in neonatal resuscitation compared to the traditional method. The results of this study support the efficacy of the 6-step LSPPDM pedagogy in the education of nursing students regarding neonatal resuscitation in a resource-limited setting.

Trial registration

Prospectively registered at ClinicalTrials.gov (NCT04748341).
The cost burden of Crohn’s disease and ulcerative colitis depending on biologic treatment status – a Danish register-based study
Authors: Alulis Sarah , Vadstrup Kasper , Olsen Jens , Jørgensen Tine Rikke , Qvist Niels , Munkholm Pia , Borsi Andras
Published: August 2021

Background

Patients diagnosed with inflammatory bowel disease may be treated with biologics, depending on several medical and non-medical factors. This study investigated healthcare costs and production values of patients treated with biologics.

Methods

This national register study included patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) between 2003 and 2015, identified in the Danish National Patient Register (DNPR). Average annual healthcare costs and production values were compared for patients receiving biologic treatment or not, and for patients initiating biologic treatment within a year after diagnosis or at a later stage. Cost estimates and production values were based on charges, fees and average gross wages.

Results

Twenty-six point one percent CD patients and ten point seven percent of UC patients were treated with biologics at some point in the study period. Of these, 46.4 and 45.5 % of patients initiated biologic treatment within the first year after diagnosis. CD and UC patients treated with biologics had higher average annual healthcare costs after diagnosis compared to patients not treated with biologics. CD patients receiving biologics early had lower production values both ten years before and eight years after treatment initiation, compared to patients receiving treatment later. UC patients receiving biologics early had lower average annual production values the first year after treatment initiation compared to UC patients receiving treatment later.

Conclusions

CD and UC patients receiving biologic treatment had higher average annual healthcare costs and lower average annual production values, compared to patients not receiving biologic treatment. The main healthcare costs drivers were outpatient visit costs and admission costs.
The current and potential uses of Electronic Medical Record (EMR) data for primary health care performance measurement in the Canadian context: a qualitative analysis
Authors: Barbazza Erica , Allin Sara , Byrnes Mary , Foebel Andrea D , Khan Tanya , Sidhom Patricia , Klazinga Niek S , Kringos Dionne S
Published: August 2021

Background

Electronic Medical Records (EMRs) are a rich data source to measure and improve quality of care. As Canadian primary health care (PHC) EMRs mature, there is increasing potential use of EMR data for performance measurement. This study identifies and describes current uses of EMR data for performance measurement and considerations to further its potential in the Canadian context.

Methods

We applied a qualitative case study design and descriptive assessment in three phases, consulting multiple data sources including scientific and grey literature, system leaders (n = 41), and clinician/researchers (n = 20). Phases included a multimethod approach to identify initiatives using EMR data for performance measurement across Canadian jurisdictions; in-depth review of current initiatives identified from a healthcare performance intelligence lens; and triangulation and thematic analysis across data sources to explore considerations for advancing performance measurement uses of EMR data in the Canadian context.

Results

Six initiatives of EMR data use for performance measurement were identified: one multi-jurisdictional; five jurisdiction-specific in the provinces of British Columbia, Manitoba and Ontario. EMR data uses were predominately for micro-level PHC physician and team performance improvement, with some use for meso-level organization/network-wide improvement. Indicator sets varied in number, though shared emphasis on chronic disease management and prevention/screening and to a lesser extent medication management. Key considerations for governing, resourcing and implementing EMR data for performance measurement were identified.

Conclusions

The extent of EMR data use for performance measurement varies across Canada. To further its potential, pan-Canadian data and privacy standards, performance intelligence competencies and renewed core PHC indicators should be prioritized. Experiences across countries, coupled with increasing momentum for performance measurement using real-world data, should be leveraged to avoid unnecessarily slow progress in Canada and abroad.
PhenoDB, GeneMatcher and VariantMatcher, tools for analysis and sharing of sequence data
Authors: Wohler Elizabeth , Martin Renan , Griffith Sean , Rodrigues Eliete da S. , Antonescu Corina , Posey Jennifer E. , Coban-Akdemir Zeynep , Jhangiani Shalini N. , Doheny Kimberly F. , Lupski James R. , Valle David , Hamosh Ada , Sobreira Nara
Published: August 2021

Background

With the advent of whole exome (ES) and genome sequencing (GS) as tools for disease gene discovery, rare variant filtering, prioritization and data sharing have become essential components of the search for disease genes and variants potentially contributing to disease phenotypes. The computational storage, data manipulation, and bioinformatic interpretation of thousands to millions of variants identified in ES and GS, respectively, is a challenging task. To aid in that endeavor, we constructed PhenoDB, GeneMatcher and VariantMatcher.

Results

PhenoDB is an accessible, freely available, web-based platform that allows users to store, share, analyze and interpret their patients’ phenotypes and variants from ES/GS data. GeneMatcher is accessible to all stakeholders as a web-based tool developed to connect individuals (researchers, clinicians, health care providers and patients) around the globe with interest in the same gene(s), variant(s) or phenotype(s). Finally, VariantMatcher was developed to enable public sharing of variant-level data and phenotypic information from individuals sequenced as part of multiple disease gene discovery projects. Here we provide updates on PhenoDB and GeneMatcher applications and implementation and introduce VariantMatcher.

Conclusion

Each of these tools has facilitated worldwide data sharing and data analysis and improved our ability to connect genes to phenotypic traits. Further development of these platforms will expand variant analysis, interpretation, novel disease-gene discovery and facilitate functional annotation of the human genome for clinical genomics implementation and the precision medicine initiative.
ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer
Authors: Brett Jamie O. , Spring Laura M. , Bardia Aditya , Wander Seth A.
Published: August 2021

In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to the backbone of therapy, estrogen deprivation by aromatase inhibition. How these mutations affect tumor sensitivity to established and novel therapies are active areas of research. These therapies include estrogen receptor-targeting agents, such as selective estrogen receptor modulators, covalent antagonists, and degraders (including tamoxifen, fulvestrant, and novel agents), and combination therapies, such as endocrine therapy plus CDK4/6, PI3K, or mTORC1 inhibition. In this review, we summarize existing knowledge surrounding the mechanisms of action of ESR1 mutations and roles in resistance to aromatase inhibition. We then analyze the recent literature on how ESR1 mutations affect outcomes in estrogen receptor-targeting and combination therapies. For estrogen receptor-targeting therapies such as tamoxifen and fulvestrant, ESR1 mutations cause relative resistance in vitro but do not clearly lead to resistance in patients, making novel agents in this category promising. Regarding combination therapies, ESR1 mutations nullify any aromatase inhibitor component of the combination. Thus, combinations using endocrine alternatives to aromatase inhibition, or combinations where the non-endocrine component is efficacious as monotherapy, are still effective against ESR1 mutations. These results emphasize the importance of investigating combinatorial resistance, challenging as these efforts are. We also discuss future directions and open questions, such as studying the differences among distinct ESR1 mutations, asking how to adjust clinical decisions based on molecular surveillance testing, and developing novel therapies that are effective against ESR1 mutations.
Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial
Authors: Rozemeijer Sander , de Grooth Harm-Jan , Elbers Paul W. G. , Girbes Armand R. J. , den Uil Corstiaan A. , Dubois Eric A. , Wils Evert-Jan , Rettig Thijs C. D. , van Zanten Arthur R. H. , Vink Roel , van den Bogaard Bas , Bosman Rob J. , Oudemans-van Straaten Heleen M. , de Man Angélique M. E.
Published: August 2021

Background

High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients.

Methods

This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations.

Discussion

Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest.

Trial registration

ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL
Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study
Authors: Day Emily , Prevost A. Toby , Sydes Matthew R. , Reddy Deepika , Shah Taimur T. , Winkler Mathias , Dudderidge Tim , Staffurth John , McCracken Stuart , Khoo Vincent , Jadav Puja , Klimowska-Nassar Natalia , Sasikaran Thiagarajah , Ahmed Hashim U. , Fiorentino Francesca
Published: August 2021

Background

Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services.

Methods and design

IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B.

IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm.

Results

This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings.

Discussion

Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage.

Trial registration

ISRCTN ISRCTN17796995. Registered on 08 October 2019
Gastric glomus tumor: a case report and review of the literature
Authors: Tsagkataki Eleni S. , Flamourakis Mathaios E. , Gkionis Ioannis G. , Giakoumakis Michail I. , Delimpaltadakis Georgios N. , Kazamias Georgios M. , Giannikaki Elpida S. , Christodoulakis Manousos S.
Published: August 2021

Introduction

Gastric glomus tumor is a rare mesenchymal neoplasm. There are only a few cases of the tumor showing malignancy, and there are no specific guidelines for the management of this entity.

Case presentation

We present the case of a 53-year-old Caucasian male who was hospitalized for anemia. Computerized tomography of the abdomen depicted a mass between the pylorus of the stomach and the first part of the duodenum. Preoperative diagnosis was achieved with pathology examination of the biopsies taken via endoscopic ultrasound and upper gastrointestinal endoscopy. An antrectomy with Roux-en-Y anastomosis and appendicectomy, due to suspicion of appendiceal mucocele, were performed. The patient had an uneventful postoperative recovery and was discharged 5 days later.

Discussion

Preoperative diagnosis of a gastric glomus tumor is difficult owing to the location of the tumor and the lack of specific clinical and endoscopic characteristics. Furthermore, it is exceptional to establish diagnosis with biopsies taken through endoscopic ultrasound or upper gastrointestinal endoscopy, prior to surgical resection. Although most glomus tumors are benign and are not known to metastasize, there are rare examples of glomus tumors exhibiting malignancy. Treatment of choice is considered wide local excision with negative margins. However, long-term follow-up is required as there is the possibility of malignancy.

Conclusion

The aim of this report is to enlighten doctors about this uncommon pathologic entity. Surgical resection is considered the golden standard therapy to establish a diagnosis and evaluate the malignant potential.
Existence and uniqueness of a finite energy solution for the mixed value problem of porous thermoelastic bodies
Authors: Marin M. , Vlase S. , Carstea C.
Published: August 2021

We consider the mixed problem with boundary and initial data in thermoelasticity of porous bodies with dipolar structure. By generalizing some known results developed by Dafermos in a more simple case of the classical theory of elasticity, we prove new theorems in which we address the issues regarding the uniqueness and existence of a solution with finite energy of the respective problem after we define this type of solution.
Enhancing learning potential score in EFL listening comprehension and self-regulation through self-regulated dynamic assessment procedures
Authors: Abdolrezapour Parisa , Ghanbari Nasim
Published: August 2021

This study aimed to integrate self-regulation strategies into dynamic assessment procedures of listening comprehension in an EFL setting and examine the possibility of raising EFL students’ listening comprehension and self-regulation skills. In addition, it explored the possibility of enhancing EFL learners’ potential scores in listening comprehension and self-regulation through applying self-regulation activities as a tool for motivating learners while being assessed. The assessment procedure was based on Vygotsky’s notion of the zone of proximal development and self-regulated intervention. The participants were 49 Iranian EFL learners in three groups: a control group, which received the institute’s regular instructional activities; a comparison group, which received dynamic assessment (DA); and an experimental group which received self-regulated dynamic assessment (SR-DA) procedures, in the form of an intervention focusing on cognitive, emotional, and behavioral self-regulation states of learners. Results of the study pointed to the potential of SR-DA for enhancing the students’ learning potential over and beyond that which is available from the DA (as offered to the comparison group) and the static testing (as offered to the control group). The results have important implications for a theoretical understanding of the mechanisms through which EFL learners develop necessary self-regulation skills in the EFL context.
The efficiency of mandibular mini-implants in reducing adverse effects of class II elastics in adolescent female patients: a single blinded, randomized controlled trial
Authors: El-Dawlatly Mostafa M. , Mabrouk Mohamed A. , ElDakroury Amr , Mostafa Yehya A.
Published: August 2021

Background

Excessive proclination of lower incisors and other undesirable consequences usually result from the use of class II elastics during orthodontic treatment. The purpose of this study was to attempt to limit the adverse effects of class II elastics by the use of mini implants placed in the mandibular arch in adolescent class II female patients.

Methods

The sample comprised 28 patients, (a mean age of 15.66 ± 2 years for intervention group and 15.1 ± 2.2 years for conventional group) with one-fourth or one-half unit class II canine relationship. The sample was divided into two equal groups. Randomization was carried out by a computer sequence generator with a 1:1 allocation ratio. In the intervention group, the mini implants were inserted between the lower second premolar and first molar, while the conventional group underwent regular class II elastics therapy. The active elastics treatment time was 8 months for both groups. Results were assessed by measurements from pre- and post-elastics lateral cephalometric radiographs.

Results

The change in L1 inclination (0.97 ± 0.92°) and L1 AP position (0.31 ± 0.63 mm) did not show a statistically significant difference between the two groups, but a statistically significant difference was found in the U1 retroclination (5.23 ± 1.92°) and U1 distal movement (4.05 ± 1.4 mm) [P ˂ 0.001] and [P ˂ 0.05] respectively in favor of the intervention group.

Conclusion

Mini-implants in conjunction with class II elastics had no skeletal effect, mainly dentoalveolar and it did not prevent the proclination of lower incisors. There was more distal movement in the upper incisors in the skeletal anchorage group which helped in enhancing the camouflaging of class II malocclusion.

Trial registration

Trial registered “FUE.REC (10)/10-2018” at the FUE registration council for clinical trials/IOP Orthodontic Program October 2018.
Complement factor D is linked to platelet activation in human and rodent sepsis
Authors: Sommerfeld O. , Dahlke K. , Sossdorf M. , Claus R. A. , Scherag A. , Bauer M. , Bloos F.
Published: August 2021

Background

The complement factor D (CFD) exerts a regulatory role during infection. However, its physiological function in coagulopathy and its impact on the course of an infection remains unclear.

Materials

Wild-type and CFD-deficient mice (n = 91) were subjected to cecal ligation and puncture to induce sepsis. At several time points, markers of coagulation and the host-immune response were determined. Furthermore, in patients (n = 79) with sepsis or SIRS, CFD levels were related to clinical characteristics, use of antiplatelet drugs and outcome.

Results

Septic CFD-deficient mice displayed higher TAT complexes (p = 0.02), impaired maximal clot firmness, but no relevant platelet drop and reduced GPIIb/IIIa surface expression on platelets (p = 0.03) compared to septic wild-type mice. In humans, higher CFD levels (non-survivors, 5.0 µg/ml to survivors, 3.6 µg/ml; p = 0.015) were associated with organ failure (SOFA score: r = 0.33; p = 0.003) and mortality (75% percentile, 61.1% to 25% percentile, 26.3%). CFD level was lower in patients with antiplatelet drugs (4.5–5.3 µg/ml) than in patients without.

Conclusion

In mice, CFD is linked to pronounced platelet activation, depicted by higher GPIIb/IIIa surface expression in wild-type mice. This might be of clinical importance since high CFD plasma concentrations were also associated with increased mortality in sepsis patients.
Pharmacokinetics and biodistribution of a novel anticancer thyrointegrin αvβ3 antagonist: triazole modified tetraiodothyroacetic acid conjugated to polyethylene glycol (P-bi-TAT)
Authors: Fujioka Kazutoshi , Godugu Kavitha , Mousa Shaker A.
Published: August 2021

We previously developed a triazole modified tetraiodothyroacetic acid (TAT) conjugated to a polyethylene glycol (PEG)-based thyrointegrin αvβ3 antagonist targeted compound, called P-bi-TAT. It exhibited potent anti-angiogenic and anticancer activities in vivo. The objective of the current study is to develop a quantitative bioanalytical method for P-bi-TAT using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to elucidate pharmacokinetics (PK) and biodistribution of P-bi-TAT in animals. We used in-source collision-induced dissociation (CID) for ionization of P-bi-TAT in the positive mode, followed by multiple reaction monitoring (MRM) for quantification. P-bi-TAT was quantified using P-mono-TAT as an internal standard because of its similarity in structure and physicochemical properties to P-bi-TAT. The LOQ for P-bi-TAT was 30 ng/μL and the recovery efficiency was 76% with the developed method. Cmax and AUC results at different doses (1, 3, 10 mg/kg) in rats suggest that P-bi-TAT is dose-dependent within the range administered. Results for Cmax and AUC in monkeys at a low dose (25 mg/kg) were comparable to those in rats. Biodistribution of subcutaneously administered P-bi-TAT in the brain of rats ranged from 7.90 to 88.7 ng/g brain weight, and levels of P-bi-TAT in the brain were dose-dependent. The results suggest that P-bi-TAT is a potential candidate as a molecular-targeted anticancer therapeutic with blood-brain barrier permeability and acceptable PK parameters. Its accumulation in organs, toxicokinetic, and pharmacodynamics needs to be further investigated.

Graphical Abstract
Transcortical approaches to large intraventricular tumors: a prospective case series of 20 patients
Authors: Elkallaf Mohamed AbdAllah , Elsaadany Waleed , Moussa Wael Mohamed Mohamed , Fayed Ahmed Abdel Aziz
Published: August 2021

Background

Large intraventricular tumors (IVTs) impose technical and surgical challenges, due to their enormous sizes, mass effect, vast extensions, and vascularity.

Objective

The authors aim at presenting their results, clinical outcomes, and the surgical strategies in the management of large IVTs through transcortical approaches.

Methods

A prospective trial was conducted at the Main Hospital of Alexandria University, Egypt, between August 2018 and October 2020 on 20 patients harboring IVTs larger than 5 cm or bilaterally represented. The variables evaluated included the extent of resection, postoperative neurological deficits, blood loss, surgical approaches, intraoperative challenges, complications, adjuvant therapies, Glasgow Outcome Scale, hydrocephalus, and cerebrospinal fluid (CSF) diversion.

Results

The study included 20 cases (9 males and 11 females). Mean age at diagnosis was 16.1 years (range 1–45). Mean follow-up was 12 months (range 9–26). Primary tumor locations were ventricular body, atrium, temporal horn, and frontal horn in 11, 5, 3, and 1 cases, respectively. Main pathologies were central neurocytomas (7 patients/35%), ependymomas (3 patients/15%), and subependymal giant cell astrocytoma (SEGA) (3 patients/15%). Excision was gross total (n = 19) and near-total (n = 1). Significant intraoperative bleeding (n = 6). Postoperative minor intraventricular hemorrhage (n = 6), subdural collections (n = 8), hydrocephalus (n = 9), memory affection (n = 4), and motor deficits (n = 4). Postoperative Glasgow Outcome Scale of 5/5 (n = 20), no mortalities were recorded. preoperative seizures (n = 7), new onset postoperative seizures (n = 2).

Conclusion

Surgical approaches to large tumors of the lateral ventricles should be tailored to the variability of tumor locations, dimensions, extensions, and the individual morbid anatomy, in addition to the surgeon’s experience and preferences. Trans-cortical approaches can provide safe surgical corridors to tackle these challenging subtypes of IVTs with good clinical outcomes, tumor resectability rates, and seizure control.
Anionic surfactant sulfate dodecyl sodium (SDS)-induced thermodynamics and conformational changes of collagen by ultrasensitive microcalorimetry
Authors: Zhang Jie , Wang Chunhua , Zhang Fengteng , Lin Wei
Published: August 2021

In this communication, sulfate dodecyl sodium (SDS)-induced thermodynamics and conformational changes of collagen were studied. We used ultrasensitive differential scanning calorimetry (US-DSC) to directly monitor the thermal transition of collagen in the presence of SDS. The results show that SDS affects the conformation and thermal stability of collagen very differently depending on its concentrations. At CSDS ≤ 0.05 mM, the enhanced thermal stability of collagen indicates the stabilizing effect by SDS. However, a further increase of SDS leads to the denaturation of collagen, verifying the well-known ability of SDS to unfold proteins. This striking difference in thermodynamics and conformational changes of collagen caused by SDS concentrations can be explained in terms of their interactions. With increasing SDS, the binding of SDS to collagen can be dominated by electrostatic interaction shifting to hydrophobic interaction, and the latter plays a key role in loosening and unfolding the triple-helix structure of collagen. The important finding in the present study is the stabilizing effect of SDS on collagen molecules at extreme low concentration.

Graphical abstract
Clinicopathologic features and therapy outcome in childhood Hodgkin’s lymphoma: a report from tertiary care center in Saudi Arabia
Authors: Alkhayat Nawaf , Alshahrani Mohammad , Elyamany Ghaleb , Sedick Qanita , Ibrahim Walid , Hamzi Hasna , Binhassan Amal , Othman Mohamed , Alshieban Saeed , Aljabry Mansour S. , Asiri Shuaa , Alzouman Muneerah , Alsuhaibani Omar , Alabbas Fahad , Alsharif Omar , Elborai Yasser
Published: August 2021

Background

Hodgkin lymphoma (HL) is lymphoid neoplasm usually affecting lymphatic system; it accounts 3.6% of cancers in Saudi Arabia. Modern treatment protocols had shown particular success rates in overall-survival (OS) and event-free-survival (EFS). In our study, we reviewed the medical records of 80 pediatric and young adolescent patients diagnosed HL from January 2006 to July 2020, treated at tertiary care hospital in Riyadh, Saudi Arabia. Demographic, clinical, and pathological data were explored. First line therapy was ABVD, COG, COPP, R-CHOP, or radiotherapy alone in 53/80 (66.4%), 24/80 (30%), 1/80 (1.2%), 1/80 (1.2%), or 1/80 (1.2%) patients; respectively. Response assessment was done by CT + / − PET scan after first 2 cycles then every 2 cycle and end of therapy. Another assessment was done if any clinical suspicion of recurrence.

Results

Median age 11 (range 3–16) years. Males to females 1.3:1. Seventy-two out of eighty (90%) patients showed first complete remission (CR1) and maintained remission for median 40 (range 7–136) months. Eight out of eighty (10%) patients showed refractory disease. Nineteen patients received salvage therapy (ICE or ESHAP/brentuximab vedotin or gemcitabine/brentuximab vedotin), 14/19 (73.7%) had 2nd complete remission (CR2) for median time 24 (ranged 9–78) months, while 5/19 (26.3%) did not show any response. Five-year OS and EFS were 95% and 75%. Two patients had 2ry malignant neoplasms, one had AML and died, the other had malignant fibrous histocytoma and still alive. None of our patients had fertility problem. Also, they did not experience chronic pulmonary or cardiotoxicity. Classic Hodgkin’s lymphoma: nodular sclerosis subtype was more prominent (55%) than mixed cellularity subtype (22.5%), which is similar to several European and US studies, lymphocyte rich (11.25%) and lymphocyte depleted (0%), while nodular lymphocyte predominant Hodgkin’s lymphoma (11.25%).

Conclusions

Our study provided unique descriptive study of childhood HL, in Saudi Arabia, with valuable insight into the long-term outcome and late toxicity. Our results are comparable to other studies in the Middle East and European countries.
Association of microalbuminuria with left ventricular dysfunction in type 2 diabetes mellitus
Authors: Mehta Jiteshri , Godbole Varsha Y. , Mehta Kedar G. , Lalithambigai A.
Published: August 2021

Background

The prevalence of diabetes mellitus is on rising trend in developing countries like India. In type 2 diabetes patients, albuminuria has been shown to predict development of dysfunction in other organ systems such as kidneys, nervous system, and retina and increase risk of cardiovascular (CV) morbidity and mortality. In this study, we plan to assess association of microalbuminuria with left ventricular dysfunction in type 2 diabetes mellitus.

Results

This cross-sectional study was conducted among 100 type 2 diabetes mellitus patients attending a tertiary care hospital in Gujarat, Western India. Based on urine albumin excretion status, they were divided in two groups of 50 each—normoalbuminuric and microalbuminuric patients. The mean FBS, PPBS, and HbA1c level was significantly lower in normoalbuminuric group compared to microalbuminuric group. There was an increase in cholesterol, triglyceride, VLDL, and LDL levels and decrease in HDL levels in microalbuminuric group as compared to normoalbuminuric group. Multivariate logistic regression analysis revealed that increase in age and a decrease in E/A ratio in patients with microalbuminuria was significantly associated with left ventricular diastolic dysfunction (LVDD).

Conclusion

The presence of microalbuminuria is associated with increased likelihood of LVDD in type 2 diabetes patients. Increase in age and decrease in E/A ratio show direct and independent association with LVDD in normotensive diabetic patients with microalbuminuria. Therefore, diabetes patients who have microalbuminuria should be regularly (or more frequently) evaluated for development of LVDD using Echocardiography. This can allow early identification of myocardial diastolic dysfunction.