bluuebunny/crossref_metadata_2025 huggingface dataset:
A Risk to Consider in the Pandemic: Weight Gain in Youths
Authors: ZENGİN Mürşide , DÜKEN Mehmet Emin , YAYAN Emriye Hilal
Published: February 2022

Objective: This study was aimed to evaluate whether the lockdown for outbreak will pose a risk in terms of weight gain in youths by determining daily activity levels, screen time and calorie amounts. Material and Method: This prospective and descriptive study was conducted during the initial stage of the Coronavirus Disease 2019 (COVID-19) lockdown. The research data were collected from youths aged 15–20 years, residing in a province in the southeast of Turkey. Research data were collected through the online interview method from a total of 67 youths residing in the family health center area of a district in the specified province. Results: The daily physical activity time was 36.41±49.09 minutes, their sleep time was 9.34±1.58 hours, and screen time was 7.70±4.20 hours of the youths. Of the youths, 44.8% had taken more necessary

than daily calories. It was found that youths were gained 2.13±2.02 kg during the initial stage of the COVID-19 lockdown. Conclusion: The results of the research showed that nearly half of the youths received more calories than they should take daily, they consumed unhealthy foods more frequently, their daily physical activity time was low, and their screen times were long during the initial stage of the COVID-19 lockdown. It was thought to be important to take necessary precautions against a possible global childhood obesity crisis in the future. In line with the research findings, it can be said that young people should be evaluated separately in terms of nutrition and weight gain in future pandemics.
Cutaneous manifestation of COVID-19: A case report
Authors: GEZER Deniz
Published: February 2022

COVID-19 disease caused by the novel coronavirus (SARS-CoV-2) results in several manifestations

involving the lungs, upper respiratory tract, gastrointestinal tract, and hematological system.

During the ongoing COVID-19 pandemic, skin lesions were observed. These lesions resolve

rapidly on treatment with corticoid creams and antihistamines. In this report, we present a case

of COVID-19 with cutaneous manifestations.
How electrolyte values affect COVID-19 patients at the time of application to the hospital?
Authors: AYDIN BAHAT Kübra , MEŞE Meral
Published: February 2022

Aim: COVID-19 disease is life threatening. we aimed to evaluated the effect of electrolyte disturbances on the course of COVID-19 disease. Material and methods: Patients hospitalized with the diagnosis of COVID-19 were included in the study. Demographic characteristics, comorbidities, symptoms, clinical course, and laboratory parameters were recorded. Results: Totally 130 COVID-19 patients, 70 (54%) of whom were female, were included in the study. The mean age was 56.6 ± 16.4 years. The most common symptom was cough (57%) and the accompanying disease hypertension (45%). 68% of the patients had hyponatremia and 29%

had hypocalcemia. 95% of the patients were discharged. 5% died. There was a relationship between the need for oxygen and advanced age, male gender, presence of diabetes mellitus, cardiovascular disease, bilateral involvement in chest CT, lymphopenia, CRP, low calcium level, hypocalcemia, and secondary infection (p = 0.024., p= 0.001, p = 0.030, p = 0.045, p = 0.002, p =0.010, p = 0.000, p = 0.022, p = 0.048, p = 0.001, respectively). There was a relationship between the need for intensive care, male gender, low calcium level, hyponatremia conclusion the presence of secondary infection. (respectively, p = 0.045, p = 0.023, p = 0.011, p = 0.001). There was a correlation between the duration of hospitalization and low calcium level and low sodium level (p = 0.026, p = 0.022). Conclusion: The severity of COVID-19 appears to be associated with

low serum sodium and calcium concentrations, and regular electrolyte monitoring can be useful in follow-up.
Lyn Phosphorylates and Controls ROR1 Surface Dynamics During Chemotaxis of CLL Cells
Authors: Dave Zankruti , Vondálová Blanářová Olga , Čada Štěpán , Janovská Pavlína , Zezula Nikodém , Běhal Martin , Hanáková Kateřina , Ganji Sri Ranjani , Krejci Pavel , Gömöryová Kristína , Peschelová Helena , Šmída Michal , Zdráhal Zbyněk , Pavlová Šárka , Kotašková Jana , Pospíšilová Šárka , Bryja Vítězslav
Published: February 2022

Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are malignancies characterized by the dependence on B-cell receptor (BCR) signaling and by the high expression of ROR1, the cell surface receptor for Wnt-5a. Both, BCR and ROR1 are therapeutic targets in these diseases and the understanding of their mutual cross talk is thus of direct therapeutic relevance. In this study we analyzed the role of Lyn, a kinase from the Src family participating in BCR signaling, as a mediator of the BCR-ROR1 crosstalk. We confirm the functional interaction between Lyn and ROR1 and demonstrate that Lyn kinase efficiently phosphorylates ROR1 in its kinase domain and aids the recruitment of the E3 ligase c-CBL. We show that ROR1 surface dynamics in migrating primary CLL cells as well as chemotactic properties of CLL cells were inhibited by Lyn inhibitor dasatinib. Our data establish Lyn-mediated phosphorylation of ROR1 as a point of crosstalk between BCR and ROR1 signaling pathways.
Identification of Ferroptosis-Related Genes as Biomarkers for Sarcoma
Authors: Guan Zhiyuan , Liu Shengfu , Luo Liying , Wu Zhong , Lu Shan , Guan Zhiqiang , Tao Kun
Published: February 2022

Sarcomas are seen as mixed-up nature with genetic and transcriptional heterogeneity and poor prognosis. Although the genes involved in ferroptosis are still unclear, iron loss is considered to be the core of glioblastoma, tumor progression, and tumor microenvironment. Here, we developed and tested the prognosis of SARC, which is a genetic marker associated with iron residues. The ferroptosis-related gene expression, one-way Cox analysis, and least-selection absolute regression algorithm (LASSO) are used to track prognostic-related genes and create risk assessment models. Finally, immune system infiltration and immune control point analysis are used to study the characteristics of the tumor microenvironment related to risk assessment. Moreover, LncRNA–miRNA–mRNA network was contributed in our studies. We determined the biomarker characteristics associated with iron degradation in gene 32 and developed a risk assessment model. ROC analysis showed that its model was accurately predicted, with 1, 2, 3, 4, and 5 years of overall survival in TCGA cohort of SARC patients. A comparative analysis of settings found that overall survival (OS) was lower in the high-risk than that in the low-risk group. The nomogram survival prediction model also helped to predict the OS of SARC patients. The nomogram survival prediction model has strong predictive power for the overall survival of SARC patients in TCGA dataset. GSEA analysis shows that high-risk groups are rich in inflammation, cancer-related symptoms, and pathological processes. High risk is related to immune cell infiltration and immune checkpoint. Our prediction model is based on SARC ferritin-related genes, which may support SARC prediction and provide potential attack points.
Sleep Disordered Breathing and Recurrent Tonsillitis Are Associated With Polymicrobial Bacterial Biofilm Infections Suggesting a Role for Anti-Biofilm Therapies
Authors: Mateus Tulia , Seppanen Elke J. , de Gier Camilla , Clark Sharon , Coates Harvey , Vijayasekaran Shyan , Prosser Karen , Wiertsema Selma P. , Fuery Angela , Kirkham Lea-Ann S. , Richmond Peter C. , Thornton Ruth B.
Published: February 2022

Background

The underlying pathogenesis of pediatric obstructive sleep disordered breathing (SDB) and recurrent tonsillitis (RT) are poorly understood but need to be elucidated to develop less invasive treatment and prevention strategies.

Methods

Children aged between 1- and 16-years undergoing adenoidectomy, tonsillectomy or adenotonsillectomy for SDB (n=40), RT alone (n=18), or both SDB and RT (SDB+RT) (n=17) were recruited with age-matched healthy controls (n=33). Total bacterial load and species-specific densities of nontypeable Haemophilus influenzae (NTHi), Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis were measured by qPCR in nasopharyngeal swabs, oropharyngeal swabs, adenoid and tonsillar tissue from children with SDB, SDB+RT and RT, and in naso- and oro- pharyngeal swabs from healthy children. A subset of tonsil biopsies were examined for biofilms using 16S rRNA FISH (n=3/group).

Results

The 5 bacterial species were detected in naso- and oro- pharyngeal samples from all children. These species were frequently detected in adenotonsillar tissue (except S. aureus, which was absent in adenoids) from children with SDB, SDB+RT and RT. NTHi and S. aureus were observed in tonsils from 66.7-88.2% and 33.3-58.8% of children respectively. Similar total and species-specific bacterial densities were observed in adenotonsillar tissue from children with SDB, SDB+RT or RT. Nasopharyngeal and oropharyngeal swabs were more likely to have multiple bacterial species co-detected than adenotonsillar tissue where one or two targeted species predominated. Polymicrobial biofilms and intracellular bacteria were observed in tonsils from children with adenotonsillar disease.

Conclusions

Antimicrobials, particularly anti-biofilm therapies, may be a strategy for managing children with SDB.
A Novel Classification for Predicting Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Zhang Dongfeng , Xing Haoran , Wang Rui , Tian Jinfan , Ju Zhiguo , Zhang Lijun , Chen Hui , He Yi , Song Xiantao
Published: February 2022

Aims

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is characterized by a low success rate and an increase in complications. This study aimed to explore a new and simple classification method based on plaque composition to predict guidewire (GW) crossing within 30 min of CTO lesions.

Methods

This study consecutively enrolled individuals undergoing attempted PCI of CTO who underwent coronary computed tomographic angiography (CCTA) within 2 months. Lesions were divided into soft and hard CTO groups according to the necrotic core proportion.

Results

In this study, 207 lesions were divided into soft (20.3%) and hard CTO (79.7%) groups according to a necrotic core percentage cutoff value of 72.7%. The rate of successful GW crossing within 30 min (57.6 vs. 85.7%, p = 0.004) and final success (73.3 vs. 95.2%, p = 0.001) were much lower in the hard CTO group. For patients with hard CTO, previous failed attempt, proximal side branch, bending > 45 degrees calcium ≥ 50% cross-sectional area (CSA), and distal reference diameter ≤ 2.5 mm were demonstrated to be associated with GW failure within 30 min. For patients with soft CTO, only blunt entry was proved to be an independent predictive factor of GW failure within 30 min.

Conclusions

Grouping CTO lesions according to the proportion of necrotic core is reasonable and necessary in predicting GW crossing within 30 min. A soft CTO with a necrotic core is more likely to be recanalized compared with a hard CTO with fibrous and/or dense calcium. Different plaque types have variable predictive factors.
Machine Learning Using a Single-Lead ECG to Identify Patients With Atrial Fibrillation-Induced Heart Failure
Authors: Luongo Giorgio , Rees Felix , Nairn Deborah , Rivolta Massimo W. , Dössel Olaf , Sassi Roberto , Ahlgrim Christoph , Mayer Louisa , Neumann Franz-Josef , Arentz Thomas , Jadidi Amir , Loewe Axel , Müller-Edenborn Björn
Published: February 2022

Aims

Atrial fibrillation (AF) and heart failure often co-exist. Early identification of AF patients at risk for AF-induced heart failure (AF-HF) is desirable to reduce both morbidity and mortality as well as health care costs. We aimed to leverage the characteristics of beat-to-beat-patterns in AF to prospectively discriminate AF patients with and without AF-HF.

Methods

A dataset of 10,234 5-min length RR-interval time series derived from 26 AF-HF patients and 26 control patients was extracted from single-lead Holter-ECGs. A total of 14 features were extracted, and the most informative features were selected. Then, a decision tree classifier with 5-fold cross-validation was trained, validated, and tested on the dataset randomly split. The derived algorithm was then tested on 2,261 5-min segments from six AF-HF and six control patients and validated for various time segments.

Results

The algorithm based on the spectral entropy of the RR-intervals, the mean value of the relative RR-interval, and the root mean square of successive differences of the relative RR-interval yielded an accuracy of 73.5%, specificity of 91.4%, sensitivity of 64.7%, and PPV of 87.0% to correctly stratify segments to AF-HF. Considering the majority vote of the segments of each patient, 10/12 patients (83.33%) were correctly classified.

Conclusion

Beat-to-beat-analysis using a machine learning classifier identifies patients with AF-induced heart failure with clinically relevant diagnostic properties. Application of this algorithm in routine care may improve early identification of patients at risk for AF-induced cardiomyopathy and improve the yield of targeted clinical follow-up.
Hybrid Technique on the Total Arch Replacement for Type A Aortic Dissection: 12-year Clinical and Radiographical Outcomes From a Single Center
Authors: Zhang Bowen , Sun Xiaogang , Liu Yanxiang , Dun Yaojun , Liang Shenghua , Yu Cuntao , Qian Xiangyang , Gao Haoyu , Ren Jie , Wang Luchen , Zhou Sangyu
Published: February 2022

Objective

Hybrid total arch replacement (HTAR) was an alternative for type A aortic dissection (TAAD). This study aimed to evaluate the clinical and radiographical outcomes of HTAR for TAAD and to evaluate the clinical outcomes of performing this procedure under mild hypothermia.

Methods

A total of 209 patients who underwent HTAR for TAAD were retrospectively analyzed and stratified into mild (n = 48) and moderate (n = 161) hypothermia groups to evaluate the effects of mild hypothermia on the clinical outcomes. Long-term clinical outcomes were evaluated by the overall survival and adverse aortic events (AAEs). A total of 176 patients with preoperative and at least one-time postoperative aortic computed tomography angiography in our institute were included for evaluating the late aortic remodeling (aortic diameter and false lumen thrombosis).

Results

The median follow-up period was 48.3 (interquartile range [IQR] = 28.4–73.7) months. The overall survival rate was 88.0, 83.2, and 77.1% at the 1, 5, and 10 years, respectively, and in the presence of death as a competing risk, the cumulative incidence of AAEs was 4.8, 9.9, and 12.1% at the 1, 5, and 10 years. The aortic diameters were stable in the descending thoracic and abdominal aorta (P > 0.05 in all the measured aortic segments). A total of 100% complete false lumen thrombosis rate in the stent covered and distal thoracic aorta were achieved at 1 year (64/64) and 4 years (18/18), respectively after HTAR. The overall composite adverse events morbidity and mortality were 18.7 and 10.0%. Mild hypothermia (31.2, IQR = 30.2–32.0) achieved similar composite adverse events morbidity (mild: 14.6 vs. moderate: 19.9%, P = 0.41) and early mortality (mild: 10.4 vs. moderate: 9.9%, P = 1.00) compared with moderate hypothermia (median 27.7, IQR = 27–28.1) group, but mild hypothermia group needed shorter cardiopulmonary bypass (mild: 111, IQR = 93–145 min vs. moderate: 136, IQR = 114–173 min, P < 0.001) and aortic cross-clamping (mild: 45, IQR = 37–56 min vs. moderate: 78, IQR = 54–107 min, P < 0.001) time.

Conclusion

Hybrid total arch replacement achieved desirable early and long-term clinical outcomes for TAAD. Performing HTAR under mild hypothermia was as safe as under moderate hypothermia. After HTAR for TAAD, dissected aorta achieved desirable aortic remodeling, presenting as stable aortic diameters and false lumen complete thrombosis. In all, HTAR is a practical treatment for TAAD.
Prevalence of Erectile Dysfunction in Patients With Abdominal Aortic Aneurysm: An Exploratory Study
Authors: de Donato Gianmarco , Pasqui Edoardo , Gargiulo Bruno , Casilli Giulia , Ferrante Giulia , Galzerano Giuseppe , Cappelli Alessandro , Palasciano Giancarlo
Published: February 2022

Introduction

Erectile dysfunction (ED) is defined as the recurrent inability to achieve and maintain a satisfactory erection for sexual intercourse. Many studies have highlighted that ED shares common cardiovascular risk factors with cardiovascular disease. No data are reported about the prevalence of ED in patients with the abdominal aortic aneurysm (AAA). The aim of our study was to investigate the preoperative information given about sexual functions of patients undergoing endovascular aneurysm repair (EVAR) and to compare it with the presence and severity of steno-occlusive atherosclerotic lesions of the pelvic arterial tree at pre-operative Computed Tomography Angiography (CTA).

Methods

We prospectively enrolled all men patients who underwent elective EVAR from September to November 2021. Preoperative ED was evaluated using the International Index of Erectile Function (IIEF-5) questionnaire. Preoperative imaging was routinely performed with CTA scan of the abdominal aorta and iliac-pelvic district. An innovative score of pelvic arterial disease associated to AAA was defined, dividing the iliac district in 4 zones attributing a grading of severity for each zone bilaterally (score ranges 0–24). Linear regression analysis was used to correlate IIEF-5 score to anatomical score of pelvic arterial steno-occlusive disease.

Results

A total of 25 patients were enrolled. Median age was 74 ± 5.3 years. IIEF-5 average score was 14.8 ± 7.1. Eight cases (32%) had severe ED; one case (4%) had moderate, five patients (20%) had mild to moderate ED; five patients (20%) had mild ED, and 6 (24%) patients had no ED. CTA evaluation revealed an average anatomical score of 7.9 ± 4.5. Pelvic disease was considered moderate-severe in 20 cases (80%) and not significant in 20% (five cases). Linear regression analysis confirmed the hypothesis that a more diseased pelvic arterial tree was correlated to a more severe ED (Y = −1.531* × + 26.35 [slope CI: −1.946 to −1.117, p < 0.0001]).

Conclusion

Although typically unreported, the prevalence of ED associated to AAA was found to be high. A vasculogenic origin of ED in patients with AAA is plausible and may be easily confirmed by the evaluation of pelvic arterial distribution at angio-CT performed for EVAR planning. Our proposed “MAPPING AND SCORING SHEET” may help to identify the vasculogenic origin of ED in AAA patients.
Association Between Adipose Tissue Proton Density Fat Fraction, Resting Metabolic Rate and FTO Genotype in Humans
Authors: Drabsch Theresa , Junker Daniela , Bayer Sandra , Wu Mingming , Held Cora , Karampinos Dimitrios C. , Hauner Hans , Holzapfel Christina
Published: February 2022

Background

The difference of proton density fat fraction (PDFF) between supraclavicular and gluteal adipose tissue might indicate the presence of brown adipose tissue (BAT). Aim of this cross-sectional study was to investigate the association between PDFF over the supraclavicular fat region as a proxy of BAT proportion and resting metabolic rate (RMR). In addition, the association between the single nucleotide polymorphism (SNP) rs1421085 at the fat mass and obesity associated (FTO) gene locus and both PDFF and RMR was investigated.

Methods

Anthropometric, clinical, and lifestyle data from 92 healthy adults (66.3% females, mean age: 36.2 ± 13.0 years, mean body mass index: 24.9 ± 5.4 kg/m2) were included in the analysis. The RMR was measured by indirect calorimetry. The magnetic resonance imaging (MRI) was used for the measurement of visceral and subcutaneous adipose tissue (VAT, SAT) volumes and for the measurement of adipose tissue PDFF.

Results

Mean RMR of the whole group was 1 474.8 ± 242.2 kcal. Genotype data was available for 90 participants. After adjustment for age, sex, weight change and fat-free mass (FFM), no association was found between supraclavicular PDFF (p = 0.346) and gluteal PDFF (p = 0.252), respectively, and RMR, whereas statistically significant evidence for a negative association between delta PDFF (difference between gluteal PDFF and supraclavicular PDFF) and RMR (p = 0.027) was obtained. No statistically significant evidence was observed for per FTO risk allele change in RMR, gluteal and supraclavicular PDFF maps or volumes of VAT and SAT.

Conclusions

Supraclavicular PDFF as a surrogate marker of BAT presence is not a determinant of RMR under basal conditions. In the present study, the FTO rs1421085 variant is not associated with either RMR or PDFF. Further studies are needed to elucidate the effect of BAT on RMR.
Acute Effects of Liothyronine Administration on Cardiovascular System and Energy Metabolism in Healthy Volunteers
Authors: Chen Shanshan , Wohlford George F. , Vecchie’ Alessandra , Carbone Salvatore , Yavuz Sahzene , Van Tassell Benjamin , Abbate Antonio , Celi Francesco S.
Published: February 2022

Context

The pharmacokinetics of liothyronine causes concerns for cardiovascular toxicity. While the effects of sustained increase in serum T3 concentrations are well described, little is known on the effects of acute changes in T3 concentrations due to rapid action of thyroid hormone.

Objective

To assess the clinical relevance of transient increase of T3 levels on cardiovascular system and energy metabolism.

Setting

Double-blind, three arms, placebo controlled, cross-over study (ClinicalTrials.gov Identifier: NCT03098433).

Study Participants

Twelve volunteers (3 females, 9 males), age 27.7 ± 5.1 years.

Intervention

Oral administration of liothyronine 0.7 mcg/kg, equimolar dose of levothyroxine (0.86 mcg/kg), or placebo in three identical study visits. Blood samples for total T3, free T4 were collected at times 0’, 60’ 120’ 180’ 240’. Continuous recording of heart rate, blood pressure, and hemodynamic data was performed using the volume clamp method. Resting energy expenditure was measured by indirect calorimetry. An echocardiogram was performed on each study visit at baseline and after the last blood sampling.

Main Outcome Measures

Changes in cardiovascular function and energy expenditure.

Results

Following the administration of liothyronine, serum T3 reached a Cmax of 421 ± 57 ng/dL with an estimated Tmax of 120 ± 26 minutes. No differences between study arms were observed in heart rate, blood pressure, hemodynamics parameters, energy expenditure, and in echocardiogram parameters.

Conclusions

The absence of measurable rapid effects on the cardiovascular system following a high dose of liothyronine supports the rationale to perform long-term studies to assess its safety and effectiveness in patients affected by hypothyroidism.
Efficacy of Dulaglutide in a Patient With Type 2 Diabetes, High Cardiovascular Risk, and HIV: A Case Report
Authors: Dardano Angela , Aragona Michele , Daniele Giuseppe , Miccoli Roberto , Del Prato Stefano
Published: February 2022

Background

Type 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available.

Case Description

A 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects.

Conclusion

This case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals.
A Novel Compound Heterozygous Mutation in the DNAH11 Gene Found in Neonatal Twins With Primary Ciliary Dyskinesis
Authors: Dong Shumei , Bei Fei , Yu Tingting , Sun Luming , Chen Xiafang , Yan Hui
Published: February 2022

Background: Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder of motile cilia. Common features of PCD include upper and lower respiratory tract disease, secretory otitis media, situs inversus and fertility problems. To date, although several PCD-associated genes have been identified, the genetic causes of most PCD cases remain elusive.

Methods: In this case study, we analyzed the clinical and genetic data of one case of monochorionic diamniotic twins which were suspected of having PCD on the basis of clinical and radiological features including situs inversus, recurrent wet cough and sinusitis as well as varying degrees of respiratory distress. Whole-exome sequencing was performed to identify variants of the DNAH11 gene in the twins. Sanger sequencing and real-time quantitative polymerase chain reaction (RT-qPCR) were used for validation of DNAH11 variants both in the patient and the twins.

Results: In the twins, we found a novel mutation at c.2436C > G (p.Y812 *) and a pathogenic deletion encompassing 2.0 Kb of 7P15.3 ([GRCh38] chr7: g.21,816,397-21,818,402). The deleted region included exons 64 and 65 of DNAH11. Sanger sequencing also revealed that the twins’ father was a carrier of heterozygous C.2436C > G and a heterozygous deletion was detected in the mother. No other clinically relevant genetic variants were identified.

Conclusion: We describe a novel DNAH11 gene compound heterozygous mutation in newborn twins with PCD and recommend that PCD diagnosis should be considered in newborns presenting with respiratory distress and/or situs inversus. Early diagnosis and treatment of PCD will help control disease progression and improve the patient’s quality of life.
Targeting Glycolysis in Alloreactive T Cells to Prevent Acute Graft-Versus-Host Disease While Preserving Graft-Versus-Leukemia Effect
Authors: Huang Ying , Zou Yujing , Jiao Yiqun , Shi Peijie , Nie Xiaoli , Huang Wei , Xiong Chuanfeng , Choi Michael , Huang Charles , Macintyre Andrew N. , Nichols Amanda , Li Fang , Li Chuan-Yuan , MacIver Nancie J. , Cardona Diana M. , Brennan Todd V. , Li Zhiguo , Chao Nelson J. , Rathmell Jeffrey C. , Chen Benny J.
Published: February 2022

Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is employed in this process. However, conflicting data have been reported regarding the requirement of glycolysis to induce T cell-mediated GVHD due to the lack of T cell-specific treatments using glycolysis inhibitors. Importantly, previous studies have not evaluated whether graft-versus-leukemia (GVL) activity is preserved in donor T cells deficient for glycolysis. As a critical component affecting the clinical outcome, it is necessary to assess the anti-tumor activity following treatment with metabolic modulators in preclinical models. In the present study, we utilized T cells selectively deficient for glucose transporter 1 (Glut1T-KO), to examine the role of glycolysis exclusively in alloreactive T cells without off-targeting effects from antigen presenting cells and other cell types that are dependent on glycolysis. We demonstrated that transfer of Glut1T-KO T cells significantly improved acute GVHD outcomes through increased apoptotic rates, impaired expansion, and decreased proinflammatory cytokine production. In addition to impaired GVHD development, donor Glut1T-KO T cells mediated sufficient GVL activity to protect recipients from tumor development. A clinically relevant approach using donor T cells treated with a small molecule inhibitor of glycolysis, 2-Deoxy-D-glucose ex vivo, further demonstrated protection from tumor development. These findings indicate that treatment with glycolysis inhibitors prior to transplantation selectively eliminates alloreactive T cells, but spares non-alloreactive T cells including those that protect against tumor growth. The present study has established a definitive role for glycolysis in acute GVHD and demonstrated that acute GVHD can be selectively prevented through targeting glycolysis.
PRR-Mediated Immune Response and Intestinal Flora Profile in Soybean Meal-Induced Enteritis of Pearl Gentian Groupers, Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂
Authors: Zhang Wei , Tan Beiping , Deng Junming , Yang Qihui , Chi Shuyan , Pang Aobo , Xin Yu , Liu Yu , Zhang Haitao
Published: February 2022

Pattern recognition receptors (PRRs) can recognize microbial-specific pathogen-associated molecular patterns, initiate signal cascade transduction, activate the expressions of host immunity and proinflammatory genes, and, ultimately, trigger an immune response against identified pathogens. The present study focused on two outcomes of feeding pearl gentian groupers with high levels of soybean meal (SBM): (1) growth performance and (2) the intestinal environment, including tissue structure, flora profile, and immune responses. Some 720 groupers were randomly divided into three groups (n = 4): (1) controls, fed a 50% fish meal feed (FM), (2) with 20% of the FM substituted with SBM (SBM20), and (3) 40% of the FM substituted with SBM (SBM40). The fish were fed these iso-nitrogenous and iso-lipidic diets for 10 weeks. They were kept in containers with 1 m3 of water under natural light and temperature levels. The experimental results demonstrate that the SBM diets significantly degraded growth performance and intestinal physiology. Typical enteritis characteristics and immune fluctuations appeared, as reflected by the enzyme activities of total superoxide dismutase and lysozyme, and the contents of immunoglobulin M, complement 3, and complement 4. 16SrDNA high-throughput sequencing showed that the intestinal flora was significantly affected, with the abundance of harmful bacteria, such as Vibrio and Streptococcus, increasing with dietary SBM level. Based on “3 + 2” full-length transcriptome sequencing, three triggered PRRs were found in the intestine: the RIG-like receptor, NOD-like receptor, and Toll-like receptor signaling pathways. The intestinal flora variations were significantly correlated with the activation of the three PRR signaling pathways by canonical correlation analysis. These culminated in the transcriptome activation of NF-κB, IRFs, and costimulatory molecules, ultimately promoting the expressions of proinflammatory cytokines, interferons (IFNs), chemokines, and other molecules vital to the innate and/or adaptive immune responses. This study provides new information for diagnosing and preventing SBMIE in aquaculture fish.
Ingestion, Immunity, and Infection: Nutrition and Viral Respiratory Tract Infections
Authors: Govers Coen , Calder Philip C. , Savelkoul Huub F. J. , Albers Ruud , van Neerven R. J. Joost
Published: February 2022

Respiratory infections place a heavy burden on the health care system, particularly in the winter months. Individuals with a vulnerable immune system, such as very young children and the elderly, and those with an immune deficiency, are at increased risk of contracting a respiratory infection. Most respiratory infections are relatively mild and affect the upper respiratory tract only, but other infections can be more serious. These can lead to pneumonia and be life-threatening in vulnerable groups. Rather than focus entirely on treating the symptoms of infectious disease, optimizing immune responsiveness to the pathogens causing these infections may help steer towards a more favorable outcome. Nutrition may have a role in such prevention through different immune supporting mechanisms. Nutrition contributes to the normal functioning of the immune system, with various nutrients acting as energy sources and building blocks during the immune response. Many micronutrients (vitamins and minerals) act as regulators of molecular responses of immune cells to infection. It is well described that chronic undernutrition as well as specific micronutrient deficiencies impair many aspects of the immune response and make individuals more susceptible to infectious diseases, especially in the respiratory and gastrointestinal tracts. In addition, other dietary components such as proteins, pre-, pro- and synbiotics, and also animal- and plant-derived bioactive components can further support the immune system. Both the innate and adaptive defense systems contribute to active antiviral respiratory tract immunity. The initial response to viral airway infections is through recognition by the innate immune system of viral components leading to activation of adaptive immune cells in the form of cytotoxic T cells, the production of neutralizing antibodies and the induction of memory T and B cell responses. The aim of this review is to describe the effects of a range different dietary components on anti-infective innate as well as adaptive immune responses and to propose mechanisms by which they may interact with the immune system in the respiratory tract.
A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice
Authors: Coria Lorena M. , Saposnik Lucas M. , Pueblas Castro Celeste , Castro Eliana F. , Bruno Laura A. , Stone William B. , Pérez Paula S. , Darriba Maria Laura , Chemes Lucia B. , Alcain Julieta , Mazzitelli Ignacio , Varese Augusto , Salvatori Melina , Auguste Albert J. , Álvarez Diego E. , Pasquevich Karina A. , Cassataro Juliana
Published: February 2022

In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.
Clinical Importance of Potential Genetic Determinants Affecting Propofol Pharmacokinetics and Pharmacodynamics
Authors: Budic Ivana , Jevtovic Stoimenov Tatjana , Pavlovic Dimitrije , Marjanovic Vesna , Djordjevic Ivona , Stevic Marija , Simic Dusica
Published: February 2022

Interindividual variability in response to drugs used in anesthesia has long been considered the rule, not the exception. It is important to mention that in anesthesiology, the variability in response to drugs is multifactorial, i.e., genetic and environmental factors interact with each other and thus affect the metabolism, efficacy, and side effects of drugs. Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. Individual differences in genetic factors [single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular transporters, and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The objective of this review (through the analysis of published research) was to systematize the influence of gene polymorphisms on the pharmacokinetics and pharmacodynamics of propofol, to explain whether and to what extent the gene profile has an impact on variations observed in the clinical response to propofol, and to estimate the benefit of genotyping in anesthesiology. Despite the fact that there has been a considerable advance in this type of research in recent years, which has been largely limited to one or a group of genes, interindividual differences in propofol pharmacokinetics and pharmacodynamics may be best explained by the contribution of multiple pathways and need to be further investigated.
Initial Evaluations of the Microtubule-Based PET Radiotracer, [11C]MPC-6827 in a Rodent Model of Cocaine Abuse
Authors: Damuka Naresh , Martin Thomas J. , Bansode Avinash H. , Krizan Ivan , Martin Conner W. , Miller Mack , Whitlow Christopher T. , Nader Michael A. , Solingapuram Sai Kiran Kumar
Published: February 2022

Purpose

Microtubules (MTs) are structural units made of α and β tubulin subunits in the cytoskeleton responsible for axonal transport, information processing, and signaling mechanisms—critical for healthy brain function. Chronic cocaine exposure affects the function, organization, and stability of MTs in the brain, thereby impairing overall neurochemical and cognitive processes. At present, we have no reliable, non-invasive methods to image MTs for cocaine use disorder (CUD). Recently we reported the effect of cocaine in patient-derived neuroblastoma SH-SY5Y cells. Here we report preliminary results of a potential imaging biomarker of CUD using the brain penetrant MT-based radiotracer, [11C]MPC-6827, in an established rodent model of cocaine self-administration (SA).

Methods

Cell uptake studies were performed with [11C]MPC-6827 in SH-SY5Y cells, treated with or without cocaine (n = 6/group) at 30 and 60 min incubations. MicroPET/CT brain scans were performed in rats at baseline and 35 days after cocaine self-administration and compared with saline-treated rats as controls (n = 4/sex). Whole-body post-PET biodistribution, plasma metabolite assay, and brain autoradiography were performed in the same rats from imaging.

Results

Cocaine-treated SH-SY5Y cells demonstrated a ∼26(±4)% decrease in radioactive uptake compared to non-treated controls. Both microPET/CT imaging and biodistribution results showed lower (∼35 ± 3%) [11C]MPC-6827 brain uptake in rats that had a history of cocaine self-administration compared to the saline-treated controls. Plasma metabolite assays demonstrate the stability (≥95%) of the radiotracer in both groups. In vitro autoradiography also demonstrated lower radioactive uptake in cocaine rats compared to the control rats. [11C]MPC-6827’s in vitro SH-SY5Y neuronal cell uptake, in vivo positron emission tomography (PET) imaging, ex vivo biodistribution, and in vitro autoradiography results corroborated well with each other, demonstrating decreased radioactive brain uptake in cocaine self-administered rats versus controls. There were no significant differences either in cocaine intake or in [11C]MPC-6827 uptake between the male and female rats.

Conclusions

This project is the first to validate in vivo imaging of the MT-associations with CUD in a rodent model. Our initial observations suggest that [11C]MPC-6827 uptake decreases in cocaine self-administered rats and that it may selectively bind to destabilized tubulin units in the brain. Further longitudinal studies correlating cocaine intake with [11C]MPC-6827 PET brain measures could potentially establish the MT scaffold as an imaging biomarker for CUD, providing researchers and clinicians with a sensitive tool to better understand the biological underpinnings of CUD and tailor new treatments.
Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis
Authors: Zhang Yizhe , Chen Sifan , Tian Weitian , Zhu Hui , Li Weiwei , Dai Wanbing , Zhang Xiao , Gu Xiyao , Su Diansan
Published: February 2022

Study Objectives

To evaluate sepsis-associated encephalopathy (SAE) research and to quantitatively and qualitatively predict research hot spots using bibliometric analysis.

Methods

We extracted relevant publications from the Web of Science Core Collection on July 28, 2021. We investigated the retrieved data by bibliometric analysis (e.g. co-cited and cluster analysis, keyword co-occurrence) using the software CiteSpace and VOSviewer, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/) and Bibliometrix to analyse and predict the trends and hot spots in this field.

Main Results

We identified 1,582 published articles and reviews on SAE from 2001 to 2021. During this period, the number of manuscripts on SAE increased steadily and peaked in 2021. The USA and China were the leading countries that had a critical impact on SAE research. Among all institutions, Vanderbilt University and Pittsburgh University held leading positions and became central in the collaboration network. Among all the journals, Critical Care Medicine published the maximum number of manuscripts in the field of SAE within 20 years. Dal-Pizzol Felipe was the most productive author (61 papers) and received the largest number of citations (930 citations). Co-citation cluster analysis revealed that the most popular terms on SAE in the manner of cluster labels were critical illness, sepsis-associated encephalopathy, polymicrobial sepsis, posterior reversible encephalopathy syndrome, rat brain, intensive care unit, prior sepsis, molecular hydrogen, inflammation drive, metabolic encephalopathies, delirium pathophysiology, and clinical neuroscience. Keyword burst detection indicated that neuroinflammation, blood-brain barrier (BBB) and mitochondria dysfunction were the current research hot spots.

Conclusions

Our study revealed that neuroinflammation, blood-brain barrier, and mitochondria dysfunction had been the research foci of SAE over the past 20 years. These have emerged as the basis for transformation from basic research to clinical application in finding effective methods for the prevention and treatment of SAE.
Study of Hepatitis E Virus-4 Infection in Human Liver-Chimeric, Immunodeficient, and Immunocompetent Mice
Authors: Collignon Laura , Verhoye Lieven , Hakze-Van der Honing Renate , Van der Poel Wim H. M. , Meuleman Philip
Published: February 2022

The hepatitis E virus (HEV) is responsible for 20 million infections worldwide per year. Although, HEV infection is mostly self-limiting, immunocompromised individuals may evolve toward chronicity. The lack of an efficient small animal model has hampered the study of HEV and the discovery of anti-HEV therapies. Furthermore, new HEV strains, infectious to humans, are being discovered. Human liver-chimeric mice have greatly aided in the understanding of HEV, but only two genotypes (HEV-1 and HEV-3) have been studied in this model. Moreover, the immunodeficient nature of this mouse model does not allow full investigation of the virus and all aspects of its interaction with the host. Recent studies have shown the susceptibility of regular and nude Balb/c mice to a HEV-4 strain (KM01). This model should allow the investigation of the interplay between HEV and the adaptive immune system of its host, and potential immune-mediated complications. Here, we assess the susceptibility of human liver-chimeric and non-humanised mice to a different HEV-4 strain (BeSW67HEV4-2008). We report that humanised mice could be readily infected with this isolate, resulting in an infection pattern comparable to HEV-3 infection. Despite these results and in contrast to KM01, non-humanised mice were not susceptible to infection with this viral strain. Further investigation, using other HEV-4 isolates, is needed to conclusively determine HEV-4 tropism and mouse susceptibility.
The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway
Authors: Zhang Yujia , Huang Qiaoyan , Wang Sichen , Liao Ziqian , Jin Haichao , Huang Shuo , Hong Xiao , Liu Yiming , Pang Jie , Shen Qing , Wang Qingcheng , Li Changyu , Ji Liting
Published: February 2022

Despite extensive research on Alzheimer’s disease (AD), its diagnosis and treatment remain challenging, and no effective therapies are currently available. Amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles are the histological characteristics of AD that have been directly linked to neuropathological events such as synaptic and neuronal cell loss. In this study, we explored whether the “JAK2-STAT3-BACE1” pathway is involved in neuroprotection conferred by the food flavouring agent β-caryophyllene (BCP). PC-12 cells with overexpressed amyloid-β protein precursor (APP) were utilised to construct an AD model in vitro, which was then split into four groups, namely control, empty vector, APP overexpression, and BCP (5, 10, and 20 μM). CCK-8 was used to evaluate cell viability, immunofluorescence was utilised to examine synaptic morphology, and quantitative real-time polymerase chain reaction and western blot were used to examine gene and protein expression levels. The relative expression levels of JAK2, STAT3, and BACE1 mRNA in the transfected PC-12 cells were found to be significantly upregulated. The cell morphology altered dramatically 72 h after transfection, becoming rounder, with a decrease in cell number. BCP exhibited the potential to dramatically increase PC-12 cell viability while protecting cell morphology. BCP inhibited APP, JAK2, STAT3, BACE1 mRNA and BACE1 protein overexpression, as well as JAK2 and STAT3 hyperphosphorylation. Molecular docking simulated the docking of BCP with JAK2, STAT3, BACE1, CB2. And JAK2 was found to be the most stable protein. In conclusion, inhibition of the “JAK2-STAT3-BACE1” signalling pathway may be one of the mechanisms through which BCP protects neurons and antagonises Aβ’s neurotoxicity.