bluuebunny/crossref_metadata_2025 huggingface dataset:
Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes
Authors: Meng Fanyu , Yu Wenjun , Niu Minjia , Tian Xiaoting , Miao Yayou , Li Xvelian , Zhou Yan , Ma Lifang , Zhang Xiao , Qian Kun , Yu Yongchun , Wang Jiayi , Huang Lin
Published: March 2023

Non-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles μL−1within a linear range of 102–108particles μL−1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.

Graphical Abstract
Establishment and validation of a prognostic nomogram for patients with early-onset stage I–II colon cancer
Authors: Li Dongdong
Published: March 2023

Background

The aims of this study were to establish and validate a nomogram model for predicting the survival of patients with early-onset stage I–II colon cancer (CC).

Methods

Data of eligible patients enrolled from 2012 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly allocated to training and validation groups in a 7:3 ratio. Significant prognostic factors were identified by univariate and multivariate analysis and a nomogram model constructed. The predictive performance of the nomogram was evaluated by the concordance index (C-index), calibration plots, and decision curve analysis.

Results

Our study cohort comprised 3528 early-onset CC patients with stage I–II disease, 2469 of whom were allocated to the training cohort and 1059 to the validation cohort. Race, age, marital status, tumor grade, tumor size, tumor stage (T stage), and chemotherapy were considered the significant predictor by univariate analysis. Race, marital status, and T stage were found to be independent prognostic factors by multivariate analysis. The C-indexes of the nomogram were 0.724 and 0.692 in the training and validation cohorts, respectively. Likewise, the calibration plots showed good agreement regarding the probability of 3- and 5-year observed and nomogram-predicted overall survival in the training group. Decision curve analysis showed that the nomogram model was clinically practical and effective. Moreover, applying the nomogram enabled dividing of the patients into two cohorts with different risk scores. The low-risk group thus created had a better survival than the high-risk group.

Conclusions

We developed and validated a meaningful prognostic nomogram model for patients with early-onset stage I–II CC that clinicians can use to make better decisions for individual patients.
Outcome domains measured in randomized controlled trials of physical activity for older adults: a rapid review
Authors: Mackey Dawn C. , Ekegren Christina L. , Baldwin Claire , Young Peter J. , Gray Samantha M. , Ciok Alex , Wong Angela
Published: March 2023

Background

Toward development of a core outcome set for randomized controlled trials (RCTs) of physical activity (PA) interventions for older adults, the purpose of this study was to identify outcome domains and subdomains (‘what’ was measured) in previously published RCTs of PA for older adults.

Methods

We conducted a rapid review and searched Ovid MEDLINE for recently- published (2015-2021), English-language, RCTs of PA interventions for older adults (mean age 60+ yrs). We limited to articles published in Web of Science top-10 journals in general and internal medicine, geriatrics and gerontology, rehabilitation, and sports science. Two reviewers independently completed eligibility screening; two other reviewers abstracted trial descriptors and study outcomes. We classified study outcomes according to the standard outcome classification taxonomy endorsed by the Core Outcome Measures in Effectiveness Trials Initiative.

Results

Our search yielded 548 articles; 67 articles were eligible to be included. Of these, 82% were efficacy/effectiveness trials, 85% included both male and female participants, and 84% recruited community-dwelling older adults. Forty percent of articles reported on interventions that involved a combination of group and individual PAs, and 60% involved a combination of PA modes (e.g., aerobic, resistance). Trial sample size ranged from 14 to 2157 participants, with median (IQR) of 94 (57-517); 28,649 participants were included across all trials. We identified 21 unique outcome domains, spanning 4/5 possible core areas (physiological/clinical; life impact; resource use; adverse events). The five most commonly reported outcome domains were physical functioning (included in n=51 articles), musculoskeletal and connective tissue (n=30), general (n=26), cognitive functioning (n=16), and emotional functioning/wellbeing (n=14). Under these five outcome domains, we further identified 10 unique outcome subdomains (e.g., fall-related; body composition; quality of life). No outcome domains or subdomains were reported consistently in all RCTs.

Conclusions

We found extensive variability in outcome domains and subdomains used in RCTs of PA for older adults, reflecting the broad range of potential health benefits derived from PA and also investigator interest to monitor a range of safety parameters related to adverse events. This study will inform development of a core outcome set to improve outcome reporting consistency and evidence quality.
Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation
Authors: Di Zazzo Erika , Rienzo Monica , Casamassimi Amelia , De Rosa Caterina , Medici Nicola , Gazzerro Patrizia , Bifulco Maurizio , Abbondanza Ciro
Published: March 2023

Background

T cell activation and programming from their naïve/resting state, characterized by widespread modifications in chromatin accessibility triggering extensive changes in transcriptional programs, is orchestrated by several cytokines and transcription regulators. PRDM1 and PRDM2 encode for proteins with PR/SET and zinc finger domains that control several biological processes, including cell differentiation, through epigenetic regulation of gene expression. Different transcripts leading to main protein isoforms with (PR +) or without (PR-) the PR/SET domain have been described. Although many studies have established the critical PRDM1 role in hematopoietic cell differentiation, maintenance and/or function, the single transcript contribution has not been investigated before. Otherwise, very few evidence is currently available on PRDM2. Here, we aimed to analyze the role of PRDM1 and PRDM2 different transcripts as mediators of T lymphocyte activation.

Methods

We analyzed the transcription signature of the main variants from PRDM1 (BLIMP1a and BLIMP1b) and PRDM2 (RIZ1 and RIZ2) genes, in human T lymphocytes and Jurkat cells overexpressing PRDM2 cDNAs following activation through different signals.

Results

T lymphocyte activation induced an early increase of RIZ2 and RIZ1 followed by BLIMP1b increase and finally by BLIMP1a increase. The “first” and the “second” signals shifted the balance towards the PR- forms for both genes. Interestingly, the PI3K signaling pathway modulated the RIZ1/RIZ2 ratio in favor of RIZ1 while the balance versus RIZ2 was promoted by MAPK pathway. Cytokines mediating different Jak/Stat signaling pathways (third signal) early modulated the expression of PRDM1 and PRDM2 and the relationship of their different transcripts confirming the early increase of the PR- transcripts. Different responses of T cell subpopulations were also observed. Jurkat cells showed that the acute transient RIZ2 increase promoted the balancing of PRDM1 forms towards BLIMP1b. The stable forced expression of RIZ1 or RIZ2 induced a significant variation in the expression of key transcription factors involved in T lymphocyte differentiation. The BLIMP1a/b balance shifted in favor of BLIMP1a in RIZ1-overexpressing cells and of BLIMP1b in RIZ2-overexpressing cells.

Conclusions

This study provides the first characterization of PRDM2 in T-lymphocyte activation/differentiation and novel insights on PRDM1 and PRDM2 transcription regulation during initial activation phases.
Exoskeleton-based training improves walking independence in incomplete spinal cord injury patients: results from a randomized controlled trial
Authors: Gil-Agudo Ángel , Megía-García Álvaro , Pons José Luis , Sinovas-Alonso Isabel , Comino-Suárez Natalia , Lozano-Berrio Vicente , del-Ama Antonio J.
Published: March 2023

Background

In recent years, ambulatory lower limb exoskeletons are being gradually introduced into the clinical practice to complement walking rehabilitation programs. However, the clinical evidence of the outcomes attained with these devices is still limited and nonconclusive. Furthermore, the user-to-robot adaptation mechanisms responsible for functional improvement are still not adequately unveiled. This study aimed to (1) assess the safety and feasibility of using the HANK exoskeleton for walking rehabilitation, and (2) investigate the effects on walking function after a training program with it.

Methods

A randomized controlled trial was conducted including a cohort of 23 patients with less than 1 year since injury, neurological level of injury (C2-L4) and severity (American Spinal Cord Injury Association Impairment Scale [AIS] C or D). The intervention was comprised of 15 one-hour gait training sessions with lower limb exoskeleton HANK. Safety was assessed through monitoring of adverse events, and pain and fatigue through a Visual Analogue Scale. LEMS, WISCI-II, and SCIM-III scales were assessed, along with the 10MWT, 6MWT, and the TUG walking tests (see text for acronyms).

Results

No major adverse events were reported. Participants in the intervention group (IG) reported 1.8 cm (SD 1.0) for pain and 3.8 (SD 1.7) for fatigue using the VAS. Statistically significant differences were observed for the WISCI-II for both the “group” factor (F = 16.75, p < 0.001) and “group-time” interactions (F = 8.87; p < 0.01). A post-hoc analysis revealed a statistically significant increase of 3.54 points (SD 2.65, p < 0.0001) after intervention for the IG but not in the CG (0.7 points, SD 1.49, p = 0.285). No statistical differences were observed between groups for the remaining variables.

Conclusions

The use of HANK exoskeleton in clinical settings is safe and well-tolerated by the patients. Patients receiving treatment with the exoskeleton improved their walking independence as measured by the WISCI-II after the treatment.
A focused review of statistical practices for relating radiation dose-volume exposure and toxicity
Authors: McDonald Andrew M. , Schneider Craig S. , Stahl John M. , Oster Robert A. , Popple Richard A. , Mayo Charles S.
Published: March 2023

Purpose

Relating dose-volume histogram (DVH) information to patient outcomes is critical for outcomes research in radiation oncology, but this is statistically challenging. We performed this focused review of DVH toxicity studies to characterize current statistical approaches and determine the need for updated reporting recommendations.

Methods and materials

We performed a focused MEDLINE search to identify studies published in 5 radiation oncology specialty journals that associated dosimetry with toxicity outcomes in humans receiving radiotherapy between 2015 and 2021. Elements abstracted from each manuscript included the study outcome, organs-at-risk (OARs) considered, DVH parameters analyzed, summary of the analytic approach, use of multivariable statistics, goodness-of-fit reporting, completeness of model reporting, assessment of multicollinearity, adjustment for multiple comparisons, and methods for dichotomizing variables. Each study was also assessed for sufficient reporting to allow for replication of results.

Results

The MEDLINE search returned 2,300 studies for review and 325 met the inclusion criteria for the analysis. DVH variables were dichotomized using cut points in 154 (47.4%) studies. Logistic regression (55.4% of studies) was the most common statistical method used to relate DVH to toxicity outcomes, followed by Cox regression (20.6%) and linear regression (12.0%). Multivariable statistical tests were performed in 226 (69.5%) studies; of these, the possibility of multicollinearity was addressed in 47.8% and model goodness-of-fit were reported in 32.6%. The threshold for statistical significance was adjusted to account for multiple comparisons in 41 of 196 (17.1%) studies that included multiple statistical comparisons. Twenty-eight (8.6%) studies were classified as missing details necessary to reproduce the study results.

Conclusions

Current practices of statistical reporting in DVH outcomes suggest that studies may be vulnerable to threats against internal and external validity. Recommendations for reporting are provided herein to guard against such threats and to promote cohesiveness among radiation oncology outcomes researchers.
Precise acetabular positioning, discrepancy in leg length, and hip offset using a new seven-axis robot-assisted total hip arthroplasty system requires no learning curve: a retrospective study
Authors: Tian Run , Duan Xudong , Kong Ning , Wang Kunzheng , Yang Pei
Published: March 2023

Objective

The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted total hip arthroplasty (RA-THA) system, and to explore whether it was able to provide greater accuracy in acetabular cup positioning, superior leg length discrepancy (LLD), and hip offset than conventional methods.

Methods

A total of 160 patients in which unilateral THA was performed in the second affiliated Hospital of Xi'an Jiaotong University from July 2021 to September 2022 were studied. The first 80 patients underwent robot-assisted THA, while conventional THA was performed on the subsequent 80 by the same team of experienced surgeons. The learning curve for the RA-THA system was evaluated using cumulative sum (CUSUM) analysis. The demographic data, preoperative clinical data, duration of surgery, postoperative Harris hip score (HHS) and postoperative radiographic data from patients that had conventional THA were compared.

Results

The 80 patients who underwent primary unilateral RA-THA comprised 42 males and 38 females and were followed up for 12 weeks. Using analysis by CUSUM, the learning curve of the RA-THA system could be divided into learning and proficiency phases, the former of which consisted of the first 17 cases. There was no significant difference between the learning and proficiency phases in terms of LLD, hip offset, or accuracy of acetabular prosthesis position in the RA-THA groups. The proportion of acetabular prostheses located in the Lewinnek safe zone was 90.5% in the proficiency group and 77.5% in the conventional group, respectively, a difference that was statistically significant (P < 0.05). The absolute error between target angle and postoperative measured angle of anteversion was statistically significant in the proficiency group and the conventional group((P < 0.05). Postoperative acetabular anteversion and LLD were 19.96 ± 5.68° and 6.00 (5.00) mm in the proficiency group, respectively, and 17.84 ± 6.81° and 8.09 (4.33) mm using conventional surgery, respectively (anteversion: P = 0.049; LLD: P < 0.001).

Conclusions

The surgical team required a learning curve of 17 cases using the RA-THA system to become proficient. There was no learning curve for other parameters, namely LLD, hip offset, or accuracy of acetabular prosthesis positioning. During the proficiency phase, the RA system was superior to conventional THA for control of leg length and accuracy of acetabular cup placement.
Protective role of FBXL19 in Streptococcus pneumoniae-induced lung injury in pneumonia immature mice
Authors: Chen Zhiqiang , Zheng Bijuan , Zhang Zhiwei , Huang Zhiyong
Published: March 2023

Objective

Streptococcus pneumoniae (Spn) is a common pathogen for pediatric pneumonia and leads to severe lung injury. This study is conducted to analyze the role of F-box and leucine rich repeat protein 19 (FBXL19) in Spn-induced lung injury in immature mice.

Methods

Immature mice were infected with Spn to record the survival rates and bacterial loads in bronchoalveolar lavage fluid. Levels of FBXL19 and FOXM1 in lung tissues were determined via real-time quantitative polymerase chain reaction or Western blotting. After the interference of FBXL19, its impacts on lung inflammatory injury were appraised by the lung wet/dry weight ratio, myeloperoxidase activity, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The binding of FBXL19 to forkhead box M1 (FOXM1) in mouse lung epithelial cells was determined. After MG132 treatment, the protein and ubiquitination levels of FOXM1 were measured. The functional rescue experiments were performed to analyze the role of FOXM1 in FBXL19-regulated lung injury.

Results

FBXL19 was downregulated while FOXM1 was upregulated in lung tissues of Spn-infected immature mice. Overexpression of FBXL19 reduced the degree of lung injury and inflammation. FBXL19 can bind to FOXM1 to reduce its protein level via ubiquitination degradation. MG132 reduced the ubiquitination and increased the protein level of FOXM1. Overexpression of FOXM1 reversed the protective role of FBXL19 overexpression in lung injury of Spn immature mice.

Conclusion

FBXL19 was downregulated by Spn and FBXL19 overexpression alleviated lung injury by inducing ubiquitination and degradation of FOXM1 in Spn immature mice.
Deferral of elective surgeries during the COVID-19 pandemic and its impact on Palestinian patients: a cross-sectional study
Authors: Atary Mousa , Abu-Rmeileh Niveen M. E.
Published: March 2023

Background

During the Covid-19 epidemic, the increased number of people seeking medical attention worsened hospital shortages. This shortage required reallocating the workforce, personal protective equipment (PPE), medical equipment, medical disposables, and hospital wards. This reallocation delayed a number of elective surgeries. This study explored the financial, physical, and psychological implications of deferring elective surgeries on Palestinians in three West Bank hospitals during the pandemic.

Methods

This cross-sectional study included 398 patients from tertiary hospitals in Palestine whose elective surgical procedures were deferred due to the COVID-19 pandemic. Between 8/8/2021 and 6/9/2021, data were collected on patients who had elective surgery deferral at three government hospitals in the West Bank of the Palestinian territories. There were five parts to the study tool; personal information, access to the health system, physical affection, financial effect, and psychological effect. Statistical analysis included a univariate, bivariate and multivariate.

Results

The healthcare system's response to the COVID-19 epidemic directly affected patients whose surgeries were deferred. The healthcare system's response was the cause of the delay in 91.5% of the cases. Orthopedic and neurological surgeries account for 48.3% of deferred surgery. Other than delayed surgeries, 30.2% of patients were unable to get additional health care services. Physically, 55.5% of patients were impacted, 45% were anxious, and 29.6% were depressed.

Conclusions

Patients who had procedures deferred as a result of the healthcare system's response to the COVID-19 epidemic were impacted physically, financially, and psychologically. There should bea better crisis management strategyto ensure that certain hospitals are able to operate regularly despite the situation.
Bi-stability and critical transitions in mental health care systems: a model-based analysis
Authors: Skinner Adam , Occhipinti Jo-An , Prodan Ante , Song Yun Ju Christine , Hickie Ian B.
Published: March 2023

Background

Delayed initiation and early discontinuation of treatment due to limited availability and accessibility of services may often result in people with mild or moderate mental disorders developing more severe disorders, leading to an increase in demand for specialised care that would be expected to further restrict service availability and accessibility (due to increased waiting times, higher out-of-pocket costs, etc.).

Methods

We developed a simple system dynamics model of the interaction of specialised services capacity and disease progression to examine the impact of service availability and accessibility on the effectiveness and efficiency of mental health care systems.

Results

Model analysis indicates that, under certain conditions, increasing services capacity can precipitate an abrupt, step-like transition from a state of persistently high unmet need for specialised services to an alternative, stable state in which people presenting for care receive immediate and effective treatment. This qualitative shift in services system functioning results from a ‘virtuous cycle’ in which increasing treatment-dependent recovery among patients with mild to moderate disorders reduces the number of severely ill patients requiring intensive and/or prolonged treatment, effectively ‘releasing’ services capacity that can be used to further reduce the disease progression rate. We present an empirical case study of tertiary-level child and adolescent mental health services in the Australian state of South Australia demonstrating that the conditions under which such critical transitions can occur apply in real-world services systems.

Conclusions

Policy and planning decisions aimed at increasing specialised services capacity have the potential to dramatically increase the effectiveness and efficiency of mental health care systems, promoting long-term sustainability and resilience in the face of future threats to population mental health (e.g., economic crises, natural disasters, global pandemics).
Uncovering gene-family founder events during major evolutionary transitions in animals, plants and fungi using GenEra
Authors: Barrera-Redondo Josué , Lotharukpong Jaruwatana Sodai , Drost Hajk-Georg , Coelho Susana M.
Published: March 2023

We present GenEra (https://github.com/josuebarrera/GenEra), a DIAMOND-fueled gene-family founder inference framework that addresses previously raised limitations and biases in genomic phylostratigraphy, such as homology detection failure. GenEra also reduces computational time from several months to a few days for any genome of interest. We analyze the emergence of taxonomically restricted gene families during major evolutionary transitions in plants, animals, and fungi. Our results indicate that the impact of homology detection failure on inferred patterns of gene emergence is lineage-dependent, suggesting that plants are more prone to evolve novelty through the emergence of new genes compared to animals and fungi.
Suture-tape augmentation of anterior cruciate ligament reconstruction: a prospective, randomised controlled trial (STACLR)
Authors: Huntington Lachlan , Griffith Andrew , Spiers Libby , Pile Rebecca , Batty Lachlan , Tulloch Scott , Tran Phong
Published: March 2023

Background

Anterior cruciate ligament (ACL) reconstruction aims to restore anteroposterior and rotatory stability to the knee following ACL injury. This requires the graft to withstand the forces applied during the process of ligamentisation and the rehabilitative period. We hypothesise that the use of suture tape augmentation of single bundle ACL reconstruction (ACLR) will reduce residual knee laxity and improve patient-reported outcomes at 2-year follow-up. We will conduct a 1:1 parallel arm single-centre randomised controlled trial comparing suture tape augmented ACLR to standard ACLR technique.

Methods

The study design will be a parallel arm 1:1 allocation ratio randomised controlled trial. Sixty-six patients aged 18 and over waitlisted for primary ACLR will be randomised. Patients requiring osteotomy and extra-articular tenodesis and who have had previous contralateral ACL rupture or repair of meniscal or cartilage pathology that modifies the post-operative rehabilitation will be excluded. The primary outcome measure will be the side-to-side difference in anterior tibial translation (measured on the GNRB arthrometer) at 24 months post-surgery. GNRB arthrometer measures will also be taken preoperatively, at 3 months and 12 months post-surgery. Secondary outcomes will include patient-reported outcome measures (PROMs) collected online, including quality of life, activity and readiness to return to sport, complication rates (return to theatre, graft failure and rates of sterile effusion), examination findings and return to sport outcomes. Participants will be seen preoperatively, at 6 weeks, 3 months, 12 months and 24 months post-surgery. Participants and those taking arthrometer measures will be blinded to allocation.

Discussion

This will be the first randomised trial to investigate the effect of suture-tape augmentation of ACLR on either objective or subjective outcome measures. The use of suture-tape augmentation in ACLR has been associated with promising biomechanical and animal-level studies, exhibiting equivalent complication profiles to the standard technique, with initial non-comparative clinical studies establishing possible areas of advantage for the technique. The successful completion of this trial will allow for an improved understanding of the in situ validity of tape augmentation whilst potentially providing a further platform for surgical stabilisation of the ACL graft.

Trial registration

Australia New Zealand Clinical Trial Registry ACTRN12621001162808. Universal Trial Number (UTN): U1111-1268-1487. Registered prospectively on 27 August 2021
Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial
Authors: Blok Siebe G. , Mousa Amne , Brouwer Michelle G. , de Grooth Harm-Jan , Neto Ary Serpa , Blans Michiel J. , den Boer Sylvia , Dormans Tom , Endeman Henrik , Roeleveld Timo , Scholten Harm , van Slobbe-Bijlsma Eline R. , Scholten Erik , Touw Hugo , van der Ven Fleur Stefanie L. I. M. , Wils Evert-Jan , van Westerloo David J. , Heunks Leo M. A. , Schultz Marcus J. , Paulus Frederique , Tuinman Pieter R.
Published: March 2023

Background

Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28.

Methods

The “effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients” (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician’s discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1–7 after randomisation and on days 1–7 after start of LUS examination; mean serum lactate on days 1–7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28.

Discussion

The CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable.

Trial registration

ClinicalTrials.gov NCT05188092. Registered since January 12, 2022
Development of core outcome sets of Food for Special Medical Purposes designed for type 2 diabetes mellitus: a study protocol
Authors: Mu Dongyu , Gong Jie , Wei Yaoyao , Chen Muxi , Yu Jiajie , Du Liang , Hu Wen
Published: March 2023

Background

The Chinese government stipulates all food for special medical purposes (FSMP) designed for specific diseases to be tested in clinical trials before approving it for registration. The process of developing core outcome sets (COSs), the minimum sets of outcomes supposed to be measured and reported, provides an economical and practical option for stakeholders to communicate and cooperate in conducting clinical trials as well as in reporting FSMP outcomes. This study uses type 2 diabetes mellitus (T2DM) as an example to develop COS for clinical trials of FSMP.

Methods

The COS for FSMP-T2DM will be divided into 3 phases and developed following COS-STAP and COS-STAD:

(1) Generate a list of relevant outcomes identified from a systematic review, in which information sources will mainly include published studies, regulatory documentation, and qualitative interviews of stakeholders. The identified outcomes will be categorized using a conceptual framework and formatted into the first round of the Delphi survey questionnaire items.

(2) At least 2 rounds of Delphi surveys will be performed among stakeholders to create the COS for FSMP-T2DM. Patients, clinical dietitians, physicians, COS researchers, journal editors, FSMP manufacturers, and regulatory representatives will be invited to score each outcome from aspects of importance.

(3) Hold a face-to-face or online consensus meeting to refine the content of the COS for FSMP-T2DM. Key stakeholders will be invited to attend the meeting to discuss and agree on the final COS.

Discussion

We have prepared an alternative solution of the Likert scale selection, Delphi survey rounds, scoring group, and consensus definitions in case of an unexpected situation.

Trial registration

COMET (1547). Registered on March 23, 2020.
Use of green fluorescent nano-sensors for the determination of furosemide in biological samples and pharmaceutical preparations
Authors: Abo Zaid Mona H. , El-Enany Nahed , Mostafa Aziza E. , Hadad Ghada M. , Belal Fathalla
Published: March 2023

Background

Carbon quantum dots (CQDs) are new class of carbon nanoparticles. Recently, they have been widely used as fluorescent probes due to their easy accessibility, optical properties and chemical inertness. Many available precursors are used in the synthesis of carbon quantum dots. The electrical and optical properties of CQDs could be enhanced by doping hetero atoms such as nitrogen or sulfur into their structure.

Objective

The current work presents the synthesis and characterization of water-soluble nitrogen doped carbon quantum dots (N-CQDs) and their use as fluorescent nano-sensors for the spectrofluorimetric determination of furosemide in its pharmaceutical preparations and spiked human plasma.

Methods

A domestic microwave was used to prepare the N-CQDs by heating a solution of sucrose and urea till complete charring (about ten minutes). The produced N-CQDs exhibit a strong emission band at 376 nm after excitation at 216 nm. Furosemide caused a quantitative quenching in the fluorescence intensity of the produced N-CQDs.

Results

The proposed method was validated according to ICH Guidelines. The method was found to be linear over the range of 0.1–1.0 µg/mL with LOQ of 0.087 µg/ml.

Conclusion

Ecofriendly nano fluorescent sensors (N-CQDs) were successfully synthesized. The size of N-CQDs was distributed in the range of 6.63 nm to 10.23 nm with an average of 8.2 nm. The produced N-CQDs were used as fluorescent probes for the estimation of furosemide in its pharmaceutical preparations as well as spiked human plasma samples.
Primary adrenal Ewing’s sarcoma family of tumors with tumor thrombus of the inferior vena cava: a case report
Authors: Atagi Kaya , Karashima Takashi , Mizutani Keisuke , Fukuhara Hideo , Fukata Satoshi , Miura Yujiro , Mitsuishi Atsuyuki , Hanazaki Kazuhiro , Uemura Sunao , Miyazaki Ryohei , Anayama Takashi , Yamane Mayuka , Sakai Mizu , Iguchi Mitsuko , Yorita Kenji , Inoue Keiji
Published: March 2023

Background

Ewing’s sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing’s sarcoma) caused by chromosomal translocations have been collectively termed Ewing’s sarcoma family of tumors. We report a rare case of primary adrenal Ewing’s sarcoma family of tumors with tumor thrombus.

Case presentation

A 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively.

Conclusion

Radical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing’s sarcoma family of tumors.
On Fejér’s inequality: generalizations and applications
Authors: Rostamian Delavar Mohsen
Published: March 2023

This paper deals with generalizations and refinements of Fejér’s inequality with some new applications. We introduce a real mapping$\mathcal{M}_{f}^{\omega}(t)$Mfω(t)and obtain some its functional properties. We present several inequalities in connection with fractional integrals and their refinements by monotone functions. We also give some inequalities related to Euler’s gamma and beta functions. Furthermore, we obtain some upper and lower bounds for generalized logarithmic mean and the expected value of random variables by using the arithmetic mean.
Association between decreased grip strength in preschool children and the COVID-19 pandemic: an observational study from 2015 to 2021
Authors: Yuki Atsumu , Tamase Yumi , Nakayama Mika
Published: March 2023

Background

Coronavirus disease 2019 (COVID-19) has reduced people’s physical activity. It is essential to accumulate knowledge regarding the influence of COVID-19 on the stimulation of physical fitness and physical functions. Several studies have reported the effects of COVID-19 on physical fitness; however, there are very few reports regarding preschoolers. This study aimed to compare the physical fitness of preschoolers before and during the COVID-19 pandemic to clarify the effects of curtailment of outings implemented to control the pandemic on physical fitness among preschoolers.

Methods

The subjects were 593 Japanese preschool children enrolled at a kindergarten during 2015–2019 and in 2021 who received a physical fitness test. Children enrolled in 2020 who did not receive a physical fitness test because of the COVID-19 pandemic were excluded. The physical fitness test included grip strength, standing long jump, and a 25-m run. The relationship between physical fitness level and survey year was analyzed using a general linear model, with grip strength and standing long jump as dependent variables, year of study as the independent variable, and sex and age in months as adjusted variables. Kruskal–Wallis test was used to analyze data for the 25-m run. Multiple comparisons were used to compare fitness levels between 2021 (during the COVID-19 pandemic) with levels in previous years.

Results

Significant relationships were found between survey year and each of grip strength (p < 0.001), standing long jump (p < 0.05), and 25-m run (p < 0.001) among the overall subjects. Grip strength was significantly lower in 2021 compared with the 2016–2019 period. Similarly, sub-stratification analysis by sex showed that grip strength was lower in 2021 than in previous survey years, in both sexes. However, there was no difference in standing long jump or 25-m run times between before and during the pandemic among the overall subjects or according to sex.

Conclusions

These findings indicate that the COVID-19 pandemic has had a negative effect on the development of muscle strength in preschoolers, and suggest the need to develop strategies that could promote the development of muscle strength of preschool children when limitations are placed on activity during prolonged infectious disease pandemics.
Novel tag-based method for measuring tailbeat frequency and variations in amplitude in fish
Authors: Warren-Myers F. , Svendsen E. , Føre M. , Folkedal O. , Oppedal F. , Hvas M.
Published: March 2023

The tailbeat frequency (TBF) together with tailbeat amplitude (TBA) of fish are tightly correlated with swimming speed. In addition, these parameters can be used as indicators of metabolic rate and general activity level, provided that appropriate calibration studies have been performed in the laboratory. If an implantable bio-logger could measure TBF and TBA, it would, therefore, have great potential as a tool to monitor swimming behaviours and bioenergetics over extended periods of time in free roaming fish within natural or farm environments. The purpose of this study was, therefore, to establish a method for deriving accurate TBF and variations in TBA from activity tags that log high-resolution acceleration data. We used 6 tagged Atlantic salmon (Salmo salar) of ≈1 kg and subjected them to two types of swim trials in a large swim tunnel system. Test speeds were either incrementally increased in 20-min intervals until steady swimming ceased, or constant speed of 60 cm s−1 was given in a 4-h sustained test. The TBFs were visually observed by camera and compared with computed values from the activity tags. In the incremental trials the TBF increased linearly with swimming speed, while it remained constant during the 4 h of sustained swimming. The TBFs measured by activity tags were within ± 0.1 beat s−1 of the visual measurements across the swim speeds tested between 30 to 80 cm s−1. Furthermore, TBF and its corresponding relative swim speed were consistent between trial type. The relative TBA increased with swimming speed as a power function, showing that the fish relies on changes in both amplitude and frequency of tail movements when swimming at higher speeds, while adjustments of amplitude only play a minor part at lower speeds. These results demonstrate that TBFs can be measured accurately via activity tags, and thus be used to infer swimming activities and bioenergetics of free roaming fish. Furthermore, it is also possible to estimate changes in TBA via activity tags which allows for more nuanced assessments of swimming patterns in free roaming fish.
Developing a novel positronium biomarker for cardiac myxoma imaging
Authors: Moskal Paweł , Kubicz Ewelina , Grudzień Grzegorz , Czerwiński Eryk , Dulski Kamil , Leszczyński Bartosz , Niedźwiecki Szymon , Stępień Ewa Ł.
Published: March 2023

Purpose

Cardiac myxoma (CM), the most common cardiac tumor in adults, accounts for 50–75% of benign cardiac tumors. The diagnosis of CM is often elusive, especially in young stroke survivors and transthoracic echocardiography (TTE) is the initial technique for the differential diagnostics of CM. Less invasive cardiac computed tomography (CT) and magnetic resonance imaging (MRI) are not available for the majority of cardiac patients. Here, a robust imaging approach, ortho-Positronium (o-Ps) imaging, is presented to determine cardiac myxoma extracted from patients undergoing urgent cardiac surgery due to unexpected atrial masses. We aimed to assess if the o-Ps atom, produced copiously in intramolecular voids during the PET imaging, serves as a biomarker for CM diagnosing.

Methods

Six perioperative CM and normal (adipose) tissue samples from patients, with primary diagnosis confirmed by the histopathology examination, were examined using positron annihilation lifetime spectroscopy (PALS) and micro-CT. Additionally, cell cultures and confocal microscopy techniques were used to picture cell morphology and origin.

Results

We observed significant shortening in the mean o-Ps lifetime in tumor with compare to normal tissues: an average value of 1.92(02) ns and 2.72(05) ns for CM and the adipose tissue, respectively. Microscopic differences between tumor samples, confirmed in histopathology examination and micro-CT, did not influenced the major positronium imaging results.

Conclusions

Our findings, combined with o-Ps lifetime analysis, revealed the novel emerging positronium imaging marker (o-PS) for cardiovascular imaging. This method opens the new perspective to facilitate the quantitative in vivo assessment of intracardiac masses on a molecular (nanoscale) level.
Personalization of 99mTc-sestamibi activity in SPECT/CT myocardial perfusion imaging with the cardiofocal SmartZoom® collimator
Authors: Verrecchia-Ramos Emilie , Morel Olivier , Beauchat Valérie , Denet Sylvie , Djibo Sidikou Abdourahamane , Ginet Merwan , Pfletschinger Estelle , Teodor Luminita , Trombowsky Maud , Verdier Jeany , Vère Christelle , Retif Paul , Mahmoud Sinan Ben
Published: March 2023

Background

Patient radioprotection in myocardial perfusion imaging (MPI)-SPECT is important but difficult to optimize. The aim of this study was to adjust injected activity according to patient size—weight or BMI—by using a cardiofocal collimator camera.

Methods

The correlation equation between size and observed counts in image was determined in patients who underwent stress Tc-99m-sestamibi MPI-SPECT/CT with a cardiofocal collimator-equipped conventional Anger SPECT/CT system. Image quality analyses by seven nuclear physicians were conducted to determine the minimum patient size-independent observed count threshold that yielded sufficient image quality for perfusion-defect diagnosis. These data generated an equation that can be used to calculate personalized activity for patients according to their size.

Results

Analysis of consecutive patients (n = 294) showed that weight correlated with observed counts better than body mass index. The correlation equation was used to generate the equation that expressed the relationship between observed counts, patient weight, and injected activity. Image quality analysis with 50 images yielded an observed count threshold of 22,000 counts. Using this threshold means that the injected activity in patients with < 100 kg would be reduced (e.g., by 67% in 45-kg patients). Patients who are heavier than 100 kg would also benefit from the use of the threshold because although the injected activity would be higher (up to 78% for 150-kg patients), good image quality would be obtained.

Conclusions

This study provided a method for determining the optimal injected activity according to patient weight without compromising the image quality of conventional Anger SPECT/CT systems equipped with a cardiofocal collimator. Personalized injected activities for each patient weight ranging from 45 to 150 kg were generated, to standardize the resulting image quality independently of patient attenuation. This approach improves patient/staff radioprotection because it reduces the injected activity for < 100-kg patients (the majority of patients).
“Black People Like Me”: A virtual conference series to engage underserved patients with asthma in patient centered outcomes research
Authors: Graham LeRoy , Hart Mary , Stinson Michael , Moise Rhoda , Mitchell Lynda , Winders Tonya A. , Gardner Donna D.
Published: March 2023

Background

In response to racial inequity in asthma, asthma-related research among diverse patients is vital. However, people from historically marginalized groups are underrepresented in clinical and patient-centered outcomes research (PCOR). The “Black People Like Me” (BPLM) virtual conference series was developed to: (1) engage Black patients with asthma and their caregivers in education and discussions about asthma, and (2) encourage involvement in PCOR. Education about COVID-19 and COVID-19 vaccination was also incorporated.

Methods

The Project Advisory Group consisting of Black patients, clergy, physicians, and a program evaluator met monthly to develop BPLM. The program consisted of free one-hour virtual sessions held monthly for 6 months. BPLM was promoted through the Allergy & Asthma Network website, emails, social media, and personal contacts with a recruitment goal of ≥ 100 Black patients with asthma or caregivers. Program evaluations, interactive polling questions during each session, and participant pre- and post-session tests were conducted.

Results

Sessions averaged 658 participants including Black patients, family members, caregivers, Black clergy, health care providers, and other concerned community. Overall, 77% of participants strongly agreed with satisfaction with the sessions. Pre- and post-tests demonstrated that participants exhibited growth in knowledge regarding asthma risk, PCOR, and PCOR research opportunities for patients, exhibited preexisting and sustained knowledge regarding COVID-19 vaccination and side effects, and demonstrated an increased sense of empowerment during healthcare visits.

Conclusions

BPLM demonstrated that a virtual platform can successfully engage Black communities. Incorporating clergy and religious organizations was critical in developing the trust of the Black community towards BPLM.
Association between diet history and symptoms of individuals having recovered from COVID-19
Authors: Sahloul Ola T. , Sahloul Talaat M.
Published: March 2023

Background

Many studies show that people who eat a balanced diet have stronger immunity. The present work aimed to identify the effects of the diet history of COVID-19 patients having recovered from the disease on the occurrence and severity of symptoms.

Methods

The study sample consisted of 346 individuals aged 20–65 years. The participants’ data and answers to an electronic questionnaire regarding their diet history and symptoms were collected. The study focused on four hard symptoms (fever, body pain, cough, and dyspnoea) to investigate the relationship between these symptoms and the consumption of specific immunity foods.

Results

Symptoms were reported by 88.1% of the participants eating none of the foods investigated, whereas 85.54% and 85.55% of the individuals with little or intensive food intake, respectively, experienced symptoms.

Conclusions

Intake of specific functional foods might slightly reduce the occurrence of some symptoms.