bluuebunny/crossref_metadata_2025 huggingface dataset:
Foot Burns and Diabetes: A Systematic Review of Current Clinical Studies and Proposal of a New Treatment Algorithm
Authors: Sharma Ayushi , Perrault David , Sean Makarewicz Nathan , Pham Tam , Sheckter Clifford , Gurtner Geoffrey
Published: February 2023

This study aims to systematically identify studies that evaluate lower extremity burn injury in the diabetic population, evaluate their clinical course and patient outcomes, and present a treatment algorithm tailored to diabetic burn patients. Our systematic review of the PubMed and Web of Science databases yielded 429 unique articles. After exclusion and inclusion criteria were applied, 59 articles were selected for evaluation. In diabetic patients, the thermal injury was largely a result of decreased awareness and education regarding heat therapies in the context of peripheral neuropathy. All noncase studies found that metrics such as hospital length of stay, ICU admission rates, rates of comorbidity, complication rates, scald injuries, infection rates, and cost of treatment were significantly increased in the diabetic burn population as compared to their nondiabetic counterparts. Where infection was present, microorganisms colonizing diabetic burn wounds were different than those found in the burn wounds of immunocompetent individuals. Operative intervention including split-skin graft, amputation, and debridement were more often utilized in diabetic burn patients. Foot burns in diabetic patients pose unique clinical risks to patients, and as such need to be an alternate treatment protocol to reflect their pathology. Education and training programs are crucial in the prevention of diabetic foot burns to avoid complications, protracted healing, and adverse outcomes. A unique algorithm can guide the unique treatment of this clinical entity.
Prospective associations between accelerometry-derived physical activity and sedentary behaviors and mortality among cancer survivors
Authors: Salerno Elizabeth A , Saint-Maurice Pedro F , Wan Fei , Peterson Lindsay L , Park Yikyung , Cao Yin , Duncan Ryan P , Troiano Richard P , Matthews Charles E
Published: February 2023

Background

Survival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors.

Methods

Participants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics and health indicators.

Results

A total of 480 participants (mean age of 68.8 years [SD = 12.4] at the time of National Health and Nutrition Examination Survey assessment) reported a history of cancer. A total of 215 deaths occurred over the follow-up period. For every 1-h/d increase in light PA and moderate to vigorous PA (MVPA), cancer survivors had 49% (HR = 0.51, 95% CI = 0.34 to 0.76) and 37% (HR = 0.63 , 95% CI = 0.40 to 0.99) lower hazards of all-cause mortality, respectively. Total PA demonstrated similar associations with statistically significantly lower hazards of death for each additional hour per day (HR = 0.68, 95% CI = 0.54 to 0.85), as did every metabolic equivalents of task-hour per day increase in total PA estimations of energy expenditure (HR = 0.88, 95% CI = 0.82 to 0.95). Conversely, more sedentary time (1 h/d) was not associated with statistically significantly higher hazards (HR = 1.08, 95% CI = 0.94 to 1.23).

Conclusions

These findings reinforce the current recommendations for cancer survivors to be physically active and underscore the continued need for widespread PA promotion for long-term survival in older cancer survivors.
Can Multisystem Inflammatory Syndrome in Children Be Managed in the Outpatient Setting? An EHR-Based Cohort Study From the RECOVER Program
Authors: Jhaveri Ravi , Webb Ryan , Razzaghi Hanieh , Schuchard Julia , Mejias Asuncion , Bennett Tellen D , Jone Pei-Ni , Thacker Deepika , Schulert Grant S , Rogerson Colin , Cogen Jonathan D , Charles Bailey L , Forrest Christopher B , Lee Grace M , Rao Suchitra ,   RECOVER consortium
Published: February 2023

Using electronic health record data combined with primary chart review, we identified seven children across nine participant pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) managed exclusively as outpatients. These findings should raise awareness of mild presentations of MIS-C and the option of outpatient management.
Risk of Admission to the Pediatric Intensive Care Unit for SARS-CoV-2 Delta and Omicron Infections
Authors: Recher Morgan , Leteurtre Stéphane , Javouhey Etienne , Morin Luc , Baudin Florent , Rambaud Jérôme , Mortamet Guillaume , Hubert Hervé , Angoulvant François , Levy Michael ,   PICURE-GFRUP Study Group
Published: February 2023

Background

The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence of French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome in children (MIS-C) during the delta and omicron variant periods.

Methods

This study used the French PICU registry to obtain data on all patients admitted to 41 French PICUs diagnosed with acute COVID-19, incidental positive SARS-CoV-2 test result, or MIS-C between August 30, 2021 and April 20, 2022. Data regarding the total number of positive SARS-CoV-2 polymerase chain reaction results according to the type of variants were obtained from the French National Public Health Agency.

Results

Of 745 children, 244 (32.8%) were admitted for acute COVID-19, 246 (33.0%) for incidental positive SARS-CoV-2 test results, and 255 (34.2%) for MIS-C. The incidence of each group was higher with delta than with omicron. The incidence rate ratios with the delta variant were 7.47 (95% CI, 4.22–13.26) for acute COVID-19, 4·78 (95% CI, 2.30–9.94) for incidental positive SARS-CoV-2 test results, and 10.46 (95% CI, 5.98–18.31) for MIS-C compared to the omicron variant. The median age was 66 (7.7–126.8) months; 314 (42%) patients had comorbidities. Patients with acute COVID-19 and incidental positive SARS-CoV-2 test results had similar proportions of comorbidities. No patient with MIS-C died, whereas the mortality rates in the acute COVID-19 and incidental positive SARS-CoV-2 test results groups were 6.8% and 3.8%, respectively.

Conclusions

The incidence of acute COVID-19, incidental positive SARS-CoV-2 test results, and MIS-C admitted to the PICU were significantly higher with the delta variant than with the omicron variant.
Transient Parvovirus B19 DNAemia After Kidney Transplantation: A 2-Sided Story
Authors: Russcher Anne , Molenaar-de Backer Marijke , de Brouwer Caroline , Dijkstra Kyra , Kers Jesper , de Vries Aiko , Zaaijer Hans , Vossen Ann , Kroes Aloysius
Published: February 2023

Parvovirus B19 (B19V) DNAemia appears to be a relatively common finding after kidney transplantation. However, not all DNAemia signifies active infection with replicating virus. This study screened 134 patients posttransplantation for B19V DNAemia and identified 2 cases in which viral DNA was present after transplantation, with the donor kidney as probable source of the DNA. In both cases intact viral particles could not be detected using an endonuclease method, indicating the presence of noninfectious DNA remnants.
Hybrid Genome Assembly of Berkeleyomyces rouxiae, an Emerging Cannabis Fungal Pathogen Causing Black Root Rot in an Aeroponic Facility
Authors: Dumigan Christopher R. , Maddock Savanna , Bray-Stone Delaney , Deyholos Michael K.
Published: February 2023

The resurged interest in cultivation of Cannabis sativa has presented an array of new challenges. Among them are the difficult-to-control pests and pathogens that infect cannabis plants. The limited methods for disease control available to cannabis growers necessitates early detection of plant pathogens, something that molecular techniques such as DNA sequencing has greatly improved. This study reports for the first time the fungal plant pathogen Berkeleyomyces rouxiae causing black root rot in high THC-containing cannabis. Aeroponically grown cannabis plants at a licenced production facility in Cranbrook BC, Canada, rapidly displayed root discoloration and rot symptoms despite testing negative for all commercially available pathogen tests. Developing sequencing-based disease diagnostics requires genomic information, so this study presents the first whole genome sequence of the multihost, widespread black root rot pathogen B. rouxiae. Hybrid genome assembly using Oxford Nanopore long-reads and Illumina short-reads yielded a genome size of 28.2 Mb represented over 404 contigs with an N50 of 267 kb. Genome annotation predicted 6,960 protein-coding genes with 59,477 functional annotations. The availability of this genome will assist in sequence-based diagnostic development, comparative genomics, and taxonomic resolution of this globally important plant pathogen.
Comparison of Single-operator Laser-assisted Ultrasound-guided Radial Arterial Cannulation in Young Children with Traditional Ultrasound Guidance: A Randomized Clinical Trial
Authors: Hou Lin , Song Xuesong , Yan Na , Zhao Zhuang , Li Zhiwen
Published: February 2023

Background

Radial artery cannulation in young children is challenging. A single-operator laser-assisted ultrasound-guidance system was invented to project the path of the target artery on the skin surface. The hypothesis was that this system would improve the first-attempt success rate of radial arterial cannulation in young pediatric patients relative to traditional ultrasound guidance.

Methods

This single-center, prospective, parallel-group, randomized controlled study enrolled pediatric patients (n = 80, age less than 2 yr) requiring radial artery cannulation during general anesthesia. The participants were randomized into the traditional ultrasound-guidance group or the single-operator laser-assisted ultrasound-guidance group. After inducing general anesthesia, ultrasound-guided radial artery cannulation was performed by two experienced operators. The primary outcome was the first-attempt success rate. The secondary outcomes included the procedure time to success within the first attempt, midmost rate of first attempt, first needle-tip position, and average number of adjustments.

Results

In total, 80 children were included in the analysis. The first-attempt success rate in the single-operator laser-assisted ultrasound-guidance group (36 of 40 [90%]) was significantly greater than that in the traditional ultrasound-guidance group (28 of 40 [70%]; absolute difference, 20% [95% CI, 2.3% to 36.6%]; P = 0.025). The median procedure time to success within the first attempt was shorter in the single-operator laser-assisted ultrasound-guidance group compared with the traditional ultrasound-guidance group (31 s [27, 36 s] vs. 46 s [39, 52 s]; P < 0.001). The incidence of hematoma in the single-operator laser-assisted ultrasound-guidance group (1 of 40, 3%) was significantly lower than that in the traditional ultrasound-guidance group (11 of 40, 28%; P = 0.002). Regarding the initial needle-tip position after skin puncture, the median score (4 [3,4] vs. 2 [2,3]; P < 0.001); position 3, 4, or 5 (38 [95%] vs. 13 [33%]; P < 0.001); and position 4 or 5 (26 [65%] vs. 5 [13%]; P < 0.001) were all in favor of single-operator laser-assisted ultrasound guidance.

Conclusions

Compared with traditional ultrasound guidance, the single-operator laser-assisted ultrasound-guided system is a useful add-on to the ultrasound dynamic needle-tip puncture technique. It improves the first-attempt success rate of radial artery cannulation in children younger than 2 yr by projecting the path of the artery on the skin and provides better procedural conditions (stable ultrasound probe).

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Association of Insurance Type With Inpatient Surgical 30-Day Readmissions, Emergency Department Visits/Observation Stays, and Costs
Authors: Jacobs Michael A. , Kim Jeongsoo , Tetley Jasmine C. , Schmidt Susanne , Brimhall Bradley B. , Mika Virginia , Wang Chen-Pin , Manuel Laura S. , Damien Paul , Shireman Paula K.
Published: February 2023

Objective:

To assess the association of Private, Medicare (MC), and Medicaid/Uninsured (MU) insurance type with 30-day emergency department visits/observation stays (EDOS), readmissions, and costs in a safety-net hospital (SNH) serving diverse socioeconomic status patients.

Background:

MC’s hospital readmission reduction program (HRRP) disproportionately penalizes SNHs.

Methods:

This retrospective cohort study used inpatient National Surgical Quality Improvement Program (2013–2019) data merged with cost data. Frailty, expanded operative stress score, case status, and insurance type were used to predict odds of EDOS and readmissions, as well as index hospitalization costs.

Results:

The cohort had 1477 Private; 1164 MC; and 3488 MU cases with a patient mean age 52.1 years [SD = 14.7] and 46.8% of the cases were performed on male patients. MU [adjusted odds ratio (aOR) = 2.69, 95% confidence interval (CI) = 2.38–3.05, P < 0.001] and MC (aOR = 1.32, 95% CI = 1.11–1.56, P = 0.001) had increased odds of urgent/emergent surgeries and complications versus Private patients. Despite having similar frailty distributions, MU compared to Private patients had higher odds of EDOS (aOR = 1.71, 95% CI = 1.39–2.11, P < 0.001), and readmissions (aOR = 1.35, 95% CI = 1.11–1.65, P = 0.004), after adjusting for frailty, OSS, and case status, whereas MC patients had similar odds of EDOS and readmissions versus Private. Hospitalization variable cost %change was increased for MC (12.5%) and MU (5.9%), but MU was similar to Private after adjusting for urgent/emergent cases.

Conclusions:

Increased rates and odds of urgent/emergent cases in MU patients drive increased odds of complications and index hospitalization costs versus Private. SNHs care for higher cost populations while receiving lower reimbursements and are further penalized by the unintended consequences of HRRP. Increasing access to care, especially for MU patients, could reduce urgent/emergent surgeries resulting in fewer complications, EDOS/readmissions, and costs.
Sleep duration and the onset of menopause in Japanese women
Authors: Nagata Chisato , Wada Keiko , Yamakawa Michiyo , Nakashima Yuma , Sugino Masaaki , Mori Tomoka
Published: February 2023

Objective

Sleep characteristics may potentially affect the hormonal environment related to follicular degeneration. The present study aimed to examine the association between sleep duration and the onset of menopause in Japanese women.

Methods

We conducted a prospective study among 3,090 premenopausal Japanese women aged 35 to 56 years derived from participants in the Takayama Study. Habitual sleep duration was determined by a self-administered questionnaire at the baseline. Menopausal status was defined as the absence of menstruation for 12 months or more. The Cox proportional hazard model was used to estimate the hazard ratio of the occurrence of menopause for each category of sleep duration (≤6, 8, and ≥9 h) as compared with 7 hours of sleep after controlling for age, parity, body mass index, smoking status, years of education, and lifelong irregular menstrual cycle.

Results

During the 10 follow-up years, 1,776 women experienced natural menopause. Sleep duration of ≤6 hours was significantly associated with decreased hazard ratio of menopause (0.88; 95% confidence interval, 0.78-0.99).

Conclusions

The data suggest that short sleep duration is associated with later onset of menopause.
Cold Versus Hot Snare Polypectomy for Colorectal Polyps
Authors: Abuelazm Mohamed , Mohamed Islam , Jaber Fouad S. , Katamesh Basant E. , Shaikhkhalil Hosam , Elzeftawy Mohamed A. , Mahmoud Abdelrahman , Afifi Ahmed M. , Abdelazeem Basel , Othman Mohamed
Published: February 2023

Background and Objective:

Endoscopic polypectomy is an excellent tool for colon cancer prevention. With the innovation of novel resection techniques, the best method is still being investigated. Hence, we aim to evaluate the efficacy and safety of cold snare polypectomy (CSP) versus hot snare polypectomy (HSP) for colorectal polyp resection.

Methods:

A systematic review and meta-analysis synthesizing evidence from randomized controlled trials retrieved from PubMed, EMBASE, WOS, SCOPUS, and CENTRAL until July 16, 2022. We pooled dichotomous outcomes using risk ratio (RR) with the corresponding CI. This review’s protocol was prospectively registered in PROSPERO with ID: CRD42022347496.

Results:

We included 18 randomized controlled trials with a total of 4317 patients and 7509 polyps. Pooled RR favored HSP regarding the complete resection rate (RR: 0.96 with 95% CI: 0.95, 1, P = 0.03) and local recurrence incidence (RR: 5.74 with 95% CI: 1.27, 25.8, P = 0.02). Pooled RR favored CSP regarding the colonoscopy time (mean difference: −6.50 with 95% CI: −7.55, −5.44, P = 0.00001) and polypectomy time (mean difference: −57.36 with 95% CI: −81.74, −32.98, P = 0.00001). There was no difference regarding the incidence of immediate bleeding (P = 0.06) and perforation (P = 0.39); however, HSP was associated with more incidence of delayed bleeding (P = 0.01), abdominal pain (P = 0.007), and postresection syndrome (P = 0.02).

Discussion:

HSP is associated with a higher complete resection and lower recurrence rates; however, HSP is also associated with a higher incidence of adverse events. Therefore, improving the complete resection rate with CSP still warrants more innovation, giving the technique safety and shorter procedure duration.
An app for predicting patient dementia classes using convolutional neural networks (CNN) and artificial neural networks (ANN): Comparison of prediction accuracy in Microsoft Excel
Authors: Ho Sam Yu-Chieh , Chien Tsair-Wei , Lin Mei-Lien , Tsai Kang-Ting
Published: February 2023

Background:

Dementia is a progressive disease that worsens over time as cognitive abilities deteriorate. Effective preventive interventions require early detection. However, there are no reports in the literature concerning apps that have been developed and designed to predict patient dementia classes (DCs). This study aimed to develop an app that could predict DC automatically and accurately for patients responding to the clinical dementia rating (CDR) instrument.

Methods:

A CDR was applied to 366 outpatients in a hospital in Taiwan, with assessments on 25 and 49 items endorsed by patients and family members, respectively. The 2 models of convolutional neural networks (CNN) and artificial neural networks (ANN) were applied to examine the prediction accuracy based on 5 classes (i.e., no cognitive decline, very mild, mild, moderate, and severe) in 4 scenarios, consisting of 74 (items) in total, 25 in patients, 49 in family, and a combination strategy to select the best in the aforementioned scenarios using the forest plot. Using CDR scores in patients and their families on both axes, patients were dispersed on a radar plot. An app was developed to predict patient DC.

Results:

We found that ANN had higher accuracy rates than CNN with a ratio of 3:1 in the 4 scenarios. The highest accuracy rate (=93.72%) was shown in the combination scenario of ANN. A significant difference was observed between the CNN and ANN in terms of the accuracy rate. An available ANN-based app for predicting DC in patients was successfully developed and demonstrated in this study.

Conclusion:

On the basis of a combination strategy and a decision rule, a 74-item ANN model with 285 estimated parameters was developed and included. The development of an app that will assist clinicians in predicting DC in clinical settings is required in the near future.
A 20-year trend of prevalence and susceptibility to trimethoprim/sulfamethoxazole of Stenotrophomonas maltophilia in a single secondary care hospital in Korea
Authors: Song Je Eun , Kim Sollip , Kwak Yee Gyung , Shin Sunghwan , Um Tae-Hyun , Cho Chong Rae , Chang Jeonghyun
Published: February 2023

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can cause serious infection. We aimed to analyze the prevalence and susceptibility rates to trimethoprim/sulfamethoxazole of S. maltophilia. We conducted a retrospective study of S. maltophilia isolates from a university hospital from 2001 to 2020. Clinical information, the numbers of isolates and susceptibility rates were analyzed by year. Susceptibility rates and changes in respiratory and non-respiratory samples were compared. 1805 S. maltophilia isolates were identified, of which 81.4% (1469/1805) were from respiratory samples. There was a male predominance and 52% of the isolates were from general wards. The average susceptibility rate was 87.7% and there was no significant annual trend (P = .519). The susceptibility rate was 88.7% in respiratory samples and 84.1% in non-respiratory samples (P = .018). Susceptibility analyses using clinical data over long periods can guide the choice of antimicrobials especially for pathogen whose treatment options are limited.
Association between HMGA1 and immunosuppression in hepatocellular carcinoma: A comprehensive bioinformatics analysis
Authors: Zhu Jie , Zheng Yongshun , Liu Yuyao , Chen Mengding , Liu Yanyan , Li Jiabin
Published: February 2023

The high mobility group A1 (HMGA1) gene is overexpressed in malignant tumors, and its expression level correlates with the progression and metastasis of tumors. However, the specific role of HMGA1 in hepatocellular carcinoma (HCC) and relevant influencing approaches in tumor immunity remain unclear. In this study, the expression and clinical significance of HMGA1 in HCC immunity were analyzed. The expression levels of HMGA1 mRNA and protein in HCC tissue and normal liver tissue were analyzed based on the cancer genome atlas, the gene expression omnibus and the Human Protein Atlas databases. The correlation between HMGA1 and clinicopathological factors was analyzed, and survival was estimated based on the expression of HMGA1. Gene set cancer analysis and the TISIDB database were used to identify tumor-infiltrating immune cells and immune inhibitors. Gene set enrichment analysis was performed to determine the involved signaling pathway. The HMGA1 genetic alterations were identified with the cBioPortal for Cancer Genomics. The expression of HMGA1 mRNA and protein was significantly higher in HCC tissue and negatively correlated with survival. Neutrophils, Th17 cells, several immune inhibitors, and signaling pathways were positively correlated with the expression of HMGA1. Amplification was the main type of genetic alteration in HMGA1. These findings demonstrate that HMGA1 can be a therapeutic target and a potential biomarker to predict the prognosis of patients with HCC. HMGA1 may affect the progression of HCC by suppressing the immune function of these patients.
A comparison of the efficacy of tocilizumab versus azathioprine for neuromyelitis optica spectrum disorder: A study protocol for systematic review and meta-analysis
Authors: Tang Qi , Yao Mengyuan , Huang Yuanyuan , Bian Jiangping , Wang Yupeng , Ji Wenbo
Published: February 2023

Background:

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory disease of the nervous system, which is frequently accompanied by a pathological humoral immune response against aquaporin-4 water channel. The most common feature of the disorder is recurrent episodes of longitudinally extensive transverse myelitis and optic neuritis. Frequent relapse leads to the gradual accumulation of neurological dysfunction. Azathioprine (AZA) is an empirical attack -preventive immunotherapies drug to prevent the relapse of NMOSD, and tocilizumab (TCZ) has been also reported reduce the activity of NMOSD. Therefore, we designed this systematic review and meta-analysis to evaluate the efficacy between TCZ and AZA in the treatment of NMOSD patients.

Methods:

This study followed the PRISMA guidelines. We searched the English literature between 2000 and 2022 by using relevant medical subject heading and entry terms in PubMed, MEDLINE, Embase and CENTRAL databases. A meta-analysis of drug efficacy was performed using expanded disability status scale score and annualized relapse rate (ARR) as the primary outcome indicators.

Results:

The literature search found a total of 1546 articles about TCZ and AZA in the treatment of NMOSD, 27 of which were included in this study after a series of screening. 930 and 148 patients with NMOSD were enrolled, who had been treated with AZA and TCZ, respectively. The pooled standardized mean difference (SMD) of expanded disability status scale score before and after AZA treated was -0.40 (95%CI: -0.50, -0.30) (I2 = 65.4%, P < .001), before and after TCZ treated was -0.84 (95%CI: -1.08, -0.60) (I2 = 45.6%, P = .076). The SMD of ARR before and after AZA treated was -1.01 (95%CI: -1.12, -0.90) (I2 = 83.4%, P < .001), before and after TCZ treated was -1.27 (95%CI: -1.52, -1.03) (I2 = 52.7%, P = .039). In addition, TCZ reduce ARR more significantly compared with AZA (P = .031).

Conclusion:

The results of this study showed that the treatment of NMOSD patients with AZA and TCZ are associated with decreased number of relapses and disability improvement as well. In addition, compared with AZA, TCZ more significantly reduce ARR.
Clinical efficacy of overground powered exoskeleton for gait training in patients with subacute stroke: A randomized controlled pilot trial
Authors: Yoo Hyun-Joon , Bae Cho Rong , Jeong Hyeonsoon , Ko Myoung-Hwan , Kang Yoon-Kyoo , Pyun Sung-Bom
Published: February 2023

Background:

To investigate the efficacy and usefulness of 12 sessions of overground robot-assisted gait training (RAGT) in subacute stroke patients.

Methods:

In this pilot study, 17 subacute stroke survivors were randomly assigned to the intervention (n = 9) and control (n = 8) groups. In addition to the conventional stroke neurorehabilitation program, the intervention group received 30 minutes of overground exoskeletal RAGT, while the control group received 30 minutes of conventional gait training by a physiotherapist. All interventions were performed in 12 sessions (3 times/week for 4 weeks). The primary aim was to assess ambulation ability using the functional ambulation category (FAC). The 10-m walk test, Berg Balance Scale, timed-up-and-go Timed-up-and-go, Fugl–Meyer assessment of lower extremity, pulmonary function test, the Korean version of the modified Barthel index, and Euro quality of life-5 dimensions (EQ-5D) were assessed. All outcomes were evaluated both before and after the intervention.

Results:

The Berg Balance Scale, Korean version of the modified Barthel index, and EQ-5D scores (P < .05) improved significantly in both groups. Only those in the RAGT group improved significantly in the FAC, timed-up-and-go, and 10-m walk test (P < .05). In the FAC and EQ-5D, the intervention group showed greater improvement than the control group (P < .05).

Conclusion:

We found that 4 weeks of overground RAGT combined with conventional training may improve walking independence and quality of life in patients with subacute stroke.
Research on the pathological mechanism of rectal adenocarcinoma based on DNA methylation
Authors: Pan Xiaoqiang , Yi Xingcheng , Lan Maozhuo , Su Xiaoyun , Zhou Fang , Wu Wei
Published: February 2023

Colorectal cancer is one of the 3 most common cancers worldwide. In this study, a weighted network-based analysis method was proposed to explore the pathological mechanisms and prognostic targets of rectal adenocarcinoma (READ) at the deoxyribonucleic acid (DNA) methylation level.

In this study, we downloaded clinical information and DNA methylation data from The Cancer Genome Atlas database. Differentially methylated gene analysis was used to identify the differential methylated genes in READ. Canonical correlation analysis was used to construct the weighted gene regulatory network for READ. Multilevel analysis and association analyses between gene modules and clinical information were used to mine key modules related to tumor metastasis evaluation. Genetic significance analysis was used to identify methylation sites in key modules. Finally, the importance of these methylation sites was confirmed using survival analysis.

DNA methylation datasets from 90 cancer tissue samples and 6 paracancerous tissue samples were selected. A weighted gene regulatory network was constructed, and a multilevel algorithm was used to divide the gene co-expression network into 20 modules. From gene ontology enrichment analysis, characteristic M was related to biological processes such as the chemotaxis of fibroblast growth factors and the activation and regulation of immune cells etc and characteristic N was associated with the regulation of cytoskeleton formation, mainly microtubules and flagella, regulation of synapses, and regulation of cell mitosis. Based on the results of survival analysis, 7 key methylation sites were found closely correlated to the survival rate of READ, such as cg04441191 (microtubule-associated protein 4 [MAP4]), cg05658717 (KSR2), cg09622330 (GRIN2A), cg10698404 (YWHAG), cg17047993 (SPAG9), cg24504843 (CEP135), and cg24531267 (CEP250). Mutational and transcriptomic level studies revealed significant differences in DNA methylation, single nucleotide polymorphism, and transcript levels between YWHAG and MAP4 in normal tissues compared to tumor tissues, and differential expression of the 2 proteins in immunohistochemistry. Therefore, potential targeting drugs were screened for these 2 proteins for molecular docking, and artenimol was found to bind to MAP4 protein and 27-hydroxycholesterol to YWHAG.

Our study found that key methylation sites played an important role in tumor metastasis and were associated with the prognosis of READ. Mutations and methylation may jointly regulate the transcription and translation of related genes, which in turn affect cancer progression. This may provide some new potential therapeutic targets and thoughts for the prognosis of READ.
Observational study of financial and non-financial conflicts of interest among the Japanese government advisory board members concerning coronavirus disease 2019
Authors: Mamada Hanano , Murayama Anju , Ozaki Akihiko , Hashimoto Takanao , Saito Hiroaki , Sawano Toyoaki , Yamashita Erika , Bhandari Divya , Shrestha Sunil , Tanimoto Tetsuya
Published: February 2023

This cross-sectional analysis aimed to assess the extent of conflicts of interest among the Japanese government coronavirus disease 2019 (COVID-19) advisory board members and elucidate the accuracy of conflicts of interest (COI) disclosure and management strategies. Using the payment data from all 79 pharmaceutical companies in Japan between 2017 and 2019 and direct research grants from the Japanese government between 2019 and 2020, we evaluated the extent of financial and non-financial COI among all 20 Japanese government COVID-19 advisory board members. The Ethic Committee of the Medical Governance Research Institute approved this study. Japanese government COVID-19 advisory board members were predominantly male (75.0%) and physicians (50.0%). Between 2019 and 2020, 2 members (10.0%) received a total of $819,244 in government research funding. Another 5 members (25.0%) received $532,127 in payments, including $276,722 in personal fees, from 31 pharmaceutical companies between 2017 and 2019. The average value of the pharmaceutical payments was $9155 (standard deviation: $12,975). Furthermore, neither the Ministry of Health, Labor, and Welfare nor the Japanese Cabinet Secretariat disclosed financial or non-financial COI with industry. Additionally, the government had no policies for managing COI among advisory board members. This study found that the Japanese government COVID-19 advisory board had financial and non-financial COI with pharmaceutical companies and the government. Furthermore, personal communication received as part of this research indicated that there were no rigorous COI management strategies for the COVID-19 advisory board members. Any government must ensure the independence of scientific advisory boards by implementing more rigorous and transparent management strategies that require the declaration and public disclosure of all COI.
Knowledge domain and dynamic patterns in multimodal molecular imaging from 2012 to 2021: A visual bibliometric analysis
Authors: Du Zhe , Wang Tianbing
Published: February 2023

Multimodal molecular imaging technologies have been widely used to optimize medical research and clinical practice. Bibliometric analysis was performed to identify global research trends, hot spots, and scientific frontiers of multimodal molecular imaging technology from 2012 to 2021. The articles and reviews related to multimodal molecular imaging were retrieved from the Web of Science Core Collection. A bibliometric study was performed using CiteSpace and VOSviewer. A total of 4169 articles and reviews from 2012 to 2021 were analyzed. An increasing trend in the number of articles on multimodal molecular imaging technology was observed. These publications mainly come from 417 institutions in 92 countries, led by the USA and China. K. Bailey Freund published the most papers amongst the publications, while R.F. Spaide had the most co-citations. A dual map overlay of the literature shows that most publications were specialized in physics/materials/chemistry, and molecular/biology/immunology. Synergistic therapy in cancer, advanced nanotechnology, and multimodal imaging in ophthalmology are new trends and developing areas of interest. A global bibliometric and visualization analysis was used to comprehensively review the published research related to multimodal molecular imaging. This study may help in understanding the dynamic patterns of multimodal molecular imaging technology research and point out the developing areas of this field.
Predictions from standard epidemiological models of consequences of segregating and isolating vulnerable people into care facilities
Authors: Hickey Joseph , Rancourt Denis G.
Published: February 2023

Objectives

Since the declaration of the COVID-19 pandemic, many governments have imposed policies to reduce contacts between people who are presumed to be particularly vulnerable to dying from respiratory illnesses and the rest of the population. These policies typically address vulnerable individuals concentrated in centralized care facilities and entail limiting social contacts with visitors, staff members, and other care home residents. We use a standard epidemiological model to investigate the impact of such circumstances on the predicted infectious disease attack rates, for interacting robust and vulnerable populations.

Design

We implement a general susceptible-infectious-recovered (SIR) compartmental model with two populations: robust and vulnerable. The key model parameters are the per-individual frequencies of within-group (robust-robust and vulnerable-vulnerable) and between-group (robust-vulnerable and vulnerable-robust) infectious-susceptible contacts and the recovery times of individuals in the two groups, which can be significantly longer for vulnerable people.

Results

Across a large range of possible model parameters including degrees of segregation versus intermingling of vulnerable and robust individuals, we find that concentrating the most vulnerable into centralized care facilities virtually always increases the infectious disease attack rate in the vulnerable group, without significant benefit to the resistant group.

Conclusions

Isolated care homes of vulnerable residents are predicted to be the worst possible mixing circumstances for reducing harm in epidemic or pandemic conditions.

Strengths and limitations of this study

We implement a simplest-possible sufficiently-realistic SIR model for an infectious respiratory disease with two interacting populations: robust and vulnerable.

We investigate the predicted attack rates for a large range of parameters representing different degrees of segregation or isolation of the minority vulnerable population.

We make broad-ranging conclusions about the consequences of segregation and isolation of vulnerable people, which apply to any epidemic model based on the SIR foundational assumptions.

Large-parameter-range exploration is needed because the actual parameter values, especially the frequencies of infectious contacts, are not well delimited by empirical measurements and are often essentially unknown.
GATA1knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation
Authors: Harper Thomas C. , Oberlick Elaine M. , Smith Tomas J. , Nunes Duncan E. , Bray Mark A. , Park Seonmi , Driscoll Corey D. , Mowbray Sarah F. , Antczak Christophe
Published: February 2023

Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at-scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targetsin vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils’ yield, purity, functionality, and maturity through the deletion of the transcription factorGATA1. GATA1knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils,GATA1KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, through CRSPR/Cas9 deletion ofCYBBwe demonstrate thatGATA1KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
Truncated titin is integrated into the human dilated cardiomyopathic sarcomere
Authors: Kellermayer Dalma , Tordai Hedvig , Kiss Balázs , Török György , Péter Dániel M. , Sayour Alex Ali , Pólos Miklós , Hartyánszky István , Szilveszter Bálint , Labeit Siegfried , Gángó Ambrus , Bedics Gábor , Bödör Csaba , Radovits Tamás , Merkely Béla , Kellermayer Miklós S.Z.
Published: February 2023

Heterozygous (HET) truncating mutations in the TTN gene (TTNtv) encoding the giant titin protein are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here we investigated 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene-sequence predictions were detected in the majority of the TTNtv samples. The total amount of expressed titin, which includes the truncated fragments, was comparable in the TTNtv+ and TTNtv-samples, indicating that titin haploinsufficiency is not the leading cause of the molecular pathogenesis. Proteomic analysis of washed cardiac myofibrils and Stimulated Emission Depletion (STED) super-resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin is structurally integrated in the sarcomere. Sarcomere lengthdependent anti-titin epitope position, shape and intensity analysis pointed at structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres, which may contribute, via faulty mechanosensor function, to the development of manifest DCM.
Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge
Authors: Schafer Christopher M. , Martin-Almedina Silvia , Kurylowicz Katarzyna , Dufton Neil , Osuna-Almagro Lourdes , Wu Meng-Ling , Johnson Charmain F. , Shah Aarti V. , Haskard Dorian O. , Buxton Andrianna , Willis Erika , Wheeler Kate , Turner Sean , Chlebicz Magdalena , Scott Rizaldy P. , Kovats Susan , Cleuren Audrey , Birdsey Graeme M. , Randi Anna M. , Griffin Courtney T.
Published: February 2023

Background

During infectious diseases, pro-inflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury.

Methods

Cytokine-dependent ubiquitination and proteasomal degradation of ERG was analyzed in cultured Human Umbilical Vein ECs (HUVECs). Systemic administration of TNFα or the bacterial cell wall component lipopolysaccharide (LPS) was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. MurineErgdeletion was genetically induced in ECs (Ergfl/fl;Cdh5(PAC)CreERT2), and multiple organs were analyzed by histology, immunostaining, and electron microscopy.

Results

In vitro, TNFα promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNFα or LPS resulted in a rapid and substantial degradation of ERG within lung ECs, but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection.Ergfl/fl;Cdh5(PAC)-CreERT2mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression ofTek, a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation.

Conclusions

Collectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.
Genetic Predictors of Blood Pressure Traits are Associated with Preeclampsia
Authors: Jasper Elizabeth A. , Hellwege Jacklyn N. , Breeyear Joseph H. , Xiao Brenda , Jarvik Gail P. , Stanaway Ian B. , Leppig Kathleen A. , Chittoor Geetha , Hayes M. Geoffrey , Dikilitas Ozan , Kullo Iftikhar J. , Holm Ingrid A. , Verma Shefali Setia , Edwards Todd L. , Velez Edwards Digna R.
Published: February 2023

Background

Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. The mechanisms leading to preeclampsia are unclear; however, there is evidence that preeclampsia is highly heritable. We evaluated the association of polygenic risk scores (PRS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture.

Methods

Participants were obtained from Vanderbilt University’s BioVU, the Electronic Medical Records and Genomics network, and the Penn Medicine Biobank. Non-Hispanic Black and White females of reproductive age with indications of pregnancy and genotype information were included. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PRS were obtained from Giri et al 2019. Associations between preeclampsia and each PRS were evaluated separately by race and study population before evidence was meta-analyzed. Prediction models were developed and evaluated using 10-fold cross validation.

Results

In the 3,504 Black and 5,009 White individuals included, the rate of preeclampsia was 15.49%. The DBP and SBP PRSs were associated with preeclampsia in Whites but not Blacks. The PP PRS was significantly associated with preeclampsia in Blacks and Whites. In trans-ancestry meta-analysis, all PRSs were associated with preeclampsia (ORDBP=1.10, 95% CI=1.02-1.17,p=7.68×10−3; ORSBP=1.16, 95% CI=1.09-1.23,p=2.23×10−6; ORPP=1.14, 95% CI=1.07-1.27,p=9.86×10−5). However, addition of PRSs to clinical prediction models did not improve predictive performance.

Conclusions

Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.
Long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: a modelling study
Authors: Hogan Alexandra B , Wu Sean L , Toor Jaspreet , Mesa Daniela Olivera , Doohan Patrick , Watson Oliver J , Winskill Peter , Charles Giovanni , Barnsley Gregory , Riley Eleanor M , Khoury David S , Ferguson Neil M , Ghani Azra C
Published: February 2023

Background

Vaccines have reduced severe disease and death from COVID-19. However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity.

Methods and findings

We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated SARS-CoV-2 transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both original and variant-adapted vaccine products, in the presence of both continuing transmission of Omicron subvariants and considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is the most efficient strategy, although large numbers of hospitalisations and deaths can be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups is more effective than continuing primary vaccination into younger ages. These findings hold if even if virus drift results in a gradual reduction in vaccine effectiveness over time due to immune escape. In a worst-case scenario where a new variant emerges that is 10% more transmissible, as severe as Delta, and exhibits substantial further immune escape, demand on health services could be similar to that experienced during 2020.

Conclusions

Regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. The cost-effectiveness of boosting is difficult to assess given the ongoing uncertainty in the likelihood of future variants and their properties but focusing vaccination in the highest-risk cohorts remains the most efficient strategy to reduce morbidity and mortality.