bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric changes in aortic root replacement using Freestyle prosthesis
Authors: Osswald Anja , Zubarevich Alina , Rad Arian Arjomandi , Vardanyan Robert , Zhigalov Konstantin , Wendt Daniel , Schmack Bastian , Mashhour Ahmed , Ruhparwar Arjang , Weymann Alexander
Published: July 2021

Background

The Medtronic Freestyle prosthesis has proven to be a promising recourse for aortic root replacement in various indications. The present study aims to evaluate clinical outcomes and geometric changes of the aorta after Freestyle implantation.

Methods

Between October 2005 and November 2020, the computed tomography angiography (CTA) data of 32 patients were analyzed in a cohort of 68 patients that underwent aortic root replacement using Freestyle prosthesis. The minimum and maximum diameters and areas of the aortic annulus, aortic root, ascending aorta, and the proximal aortic arch were measured at a plane perpendicular to the long axis of the aorta using 3D multiplanar reconstruction in both the preoperative (n = 32) and postoperative (n = 10) CTAs. Moreover, volumetric changes of the aortic root and ascending aorta were quantified.

Results

Mean age was 64.6 ± 10.6 years. Indications for surgery using Freestyle prosthesis were combined aortic valve pathologies, aortic aneurysm or dissection, and endocarditis, with concomitant surgery occurring in 28 out of 32 patients. In-hospital mortality was 18.6%.

Preoperative diameter and area measurements of the aortic annulus strongly correlated with the implanted valve size (p < 0.001). Bicuspid valve was present in 28.1% of the patients. Diameter and areas of the aortic root decreased after freestyle implantation, resulting in a reduction of the aortic root volume (45.6 ± 26.3 cm3to 18.7 ± 4.5 cm3,p = 0.029). Volume of the aortic root and the ascending aorta decreased from 137.3 ± 65.2 cm3to 54.5 ± 21.1 cm3after Freestyle implantation (p = 0.023).

Conclusion

Implantation of the Freestyle prosthesis presents excellent results in restoring the aortic geometry. Preoperative CTA measurements are beneficial to the surgical procedure and valve selection and therefore, if available, should be considered in pre-operative planning.
Clinical analysis of redo aortic root replacement after cardiac surgery: a retrospective study
Authors: Deng Jianying , Zhong Qianjin
Published: July 2021

Objectives

To explore the etiology, previous cardiac procedure methods and outcomes of redo aortic root replacement after cardiac surgery.

Methods

A retrospective analysis of 41 patients who underwent aortic root replacement surgery in our hospital from February 2010 to February 2020 who underwent at least one cardiac surgery in the past, including 27 males and 14 females, with an average age of 49.5 ± 10.2 years old. Indications for reoperation include: aortic sinus dilation and ascending aortic aneurysm in 20 cases (48.8%), recurrent aortic dissection in 7 cases (17.1%), pseudoaneurysm of aortic root in 4 cases (9.8%), prosthetic valve endocarditis in 5 cases (12.2%) and paravalvular leakage in 5 cases (12.2%). According to whether the previous procedure involved aortic root surgery, they were divided into 2 groups, namely aortic root surgery-involved (ARS) group and non-aortic root surgery-involved (NRS) group. After the patients were discharged from hospitals, follow-ups were carried out through outpatient clinic or telephone for 5 years. Kaplan-Meier was used for survival analysis.

Results

All patients underwent Bentall procedure with a median sternum incision. Six patients (14.6%) died during the postoperative hospitalization and 3 patients (8.6%) died during the follow-up. The 1-year, 3-year, and 5-year survival in ARS group were 92.6, 92.6, and 92.6%, respectively; the 1-year, 3-year, and 5-year survival in NRS group were 100, 85.7, and 85.7%, respectively. There was no statistical difference between the two groups in the cause of redo aortic root replacement, procedure time, postoperative complications, postoperative hospital stay, hospital mortality, and 5-year cumulative survival (p > 0.05).

Conclusions

Redo aortic root replacement is difficult and high risk. Bentall procedure is still a reliable surgical option for redo aortic root replacement, with good short- and mid-term results. The prognosis of redo aortic root replacement is not necessarily related to the etiology of patient’s surgery and the methods of previous cardiac procedure.
Clinical effect of dexmedetomidine combined with sufentanil on postoperative analgesia for transthoracic device closure of ventricular septal defects in children with ultrafast track anesthesia
Authors: Wang Jing , Xie Wen-Peng , Lei Yu-Qing , Wang Zeng-Chun , Cao Hua , Chen Qiang
Published: July 2021

Background

To observe the effect of combining dexmedetomidine with sufentanil on postoperative analgesia in children who underwent transthoracic device closure of ventricular septal defects (VSDs) with ultrafast track anesthesia.

Methods

This was a retrospective study. Eighty-seven children who underwent transthoracic device closure of VSDs were retrospectively analyzed. Patients were divided into three groups based on the different drugs used for postoperative patient-controlled analgesia.

Results

No statistically significant differences in hemodynamic parameters were noted among the three groups after surgery (p > 0.05). The FLACC score in the SD2 group was significantly greater than those in the S groups and SD1 groups after surgery (p < 0.001). The Ramsay score in the S group was significantly lower than that of the SD1 and SD2 groups at 6 h (p < 0.001 and p = 0.003), 12 h (p = 0.002 and p = 0.012), and 24 h (p < 0.001 and p < 0.001) after surgery. The pressing frequency of the analgesic pump 48 h after the operation in the SD2 group was significantly greater than that in the other two groups (p < 0.05). The incidences of respiratory depression, nausea, and vomiting in the S group were significantly greater than those in the SD1 and SD2 groups (p < 0.05).

Conclusion

The combination of 0.04 μg/kg/h dexmedetomidine and 0.04 μg/kg/h sufentanil intravenous analgesia was more effective than the other two analgesic strategies in children who underwent transthoracic device closure of ventricular septal defects (VSDs) with ultrafast track anesthesia.
Assessment of the reporting quality of randomised controlled trials of massage
Authors: Zhang Xuan , Zhang Lin , Xiong Weifeng , Wang Xihong , Zhou Xiaohan , Zhao Chen , Tian Guihua , Shang Hongcai , Wu Taixiang , Miao Jiangxia , Bian Zhaoxiang
Published: July 2021

Objective

To assess the reporting quality of randomised controlled trials (RCTs) of massage, particularly whether necessary elements related to massage interventions were adequately reported.

Methods

A total of 8 electronic databases were systematically searched for massage RCTs published in English and Chinese from the date of their inception to June 22, 2020. Quality assessment was performed using three instruments, namely the CONSORT (Consolidated Standards of Reporting Trials) 2010 Checklist (37 items), the CONSORT Extension for NPT (Nonpharmacologic Treatments) 2017 checklist (18 items), and a self-designed massage-specific checklist (16 items) which included massage rationale, intervention and control group details. Descriptive statistics were additionally used to analyse the baseline characteristics of included trials.

Results

A total of 2,447 massage RCTs were identified, of which most (96.8%) were distributed in China. For the completeness of CONSORT, NPT Extension, and massage-specific checklists, the average reporting percentages were 50%, 10% and 45%, respectively. Of 68 assessed items in total (exclusion of 3 repeated items on intervention), 42 were poorly presented, including 18 CONSORT items, 15 NPT items, and 9 massage-specific items. Although the overall quality of reporting showed slightly improvement in articles published after 2010, the international (English) journals presented a higher score of the CONSORT and NPT items, while the Chinese journals were associated with the increased score of massage-specific items.

Conclusion

The quality of reporting of published massage RCTs is variable and in need of improvement. Reporting guideline “CONSORT extension for massage” should be developed.
Shenzhi Jiannao formula ameliorates vascular dementia in vivo and in vitro by inhibition glutamate neurotoxicity via promoting clathrin-mediated endocytosis
Authors: Tian Danfeng , Guo Yangyang , Zhang Dandan , Gao Qiang , Liu Ganlu , Lin Jingfeng , Chang Ze , Wang Yuchun , Su Rui , Han Zhenyun
Published: July 2021

Background

Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B andN-methyl-d-aspartic acid receptor 1 (NMDAR1) proteins play a vital role in endocytosis of synaptic vesicles in neurons and glutamate over accumulation. Previous researches have been confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic and neuroprotective effect in VD, but the underlying mechanisms are still unclear. In this study, we aimed to explore the effect of SZJN formula on cognitive impairment and glutamate excitotoxicity via clathrin-mediated endocytosis (CME) in vivo and in vitro.

Methods

SZJN formula consists ofPanax ginsengC.A.Mey.,Anemarrhena asphodeloidesBunge, andPaeonia anomalasubsp.veitchii(Lynch) D.Y.Hong & K.Y.Pan. All herbs were prepared into granules. Both common carotid arteries were permanent occluded (2‐vessel occlusion, 2VO) in male Sprague Dawley (SD) rats to model VD. One day after operation, the rats began daily treatment with SZJN formula for 2 weeks. The neuroprotective effects of SZJN formula was subsequently assessed by the novel object recognition test, Morris water maze, hematoxylin–eosin (HE) staining and Nissl staining. Glutamate cytotoxicity was assessed by detecting cell viability and cell death of PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, and quantitative real‐time PCR were used to detect the expression levels of clathrin, RAB5B, and NMDAR1.

Results

Administration of SZJN formula effectively improved short-term memory and spatial memory. SZJN formula treatment significantly reduced hippocampal neuronal loss, and recovered the arrangement and morphology of neurons and Nissl bodies. Moreover, SZJN formula promoted the proliferation of PC12 cells and inhibited glutamate-induced cell death. The down-regulation of clathrin and RAB5B, as well as the upregulation of NMDAR1 in the brain induced by 2VO or glutamate was also notably reversed by SZJN formula at both the protein and mRNA levels, which may contribute to SZJN formula induced improved neurological function.

Conclusions

Taken together, our findings provide evidence that the neuroprotective effects of SZJN formula in experimental VD maybe mediated through promoting the expression of clathrin-mediated endocytosis and reducing NMDARs‐associated glutamate excitotoxicity. SZJN formula serves as a promising alternative therapy and may be a useful herbal medicine for preventing progression of VD.

Graphic abstract
Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy
Authors: Freigang Maren , Steinacker Petra , Wurster Claudia Diana , Schreiber-Katz Olivia , Osmanovic Alma , Petri Susanne , Koch Jan Christoph , Rostásy Kevin , Falkenburger Björn , Ludolph Albert Christian , Otto Markus , Hermann Andreas , Günther René
Published: July 2021

Background

Studies regarding the impact of (neuro)inflammation and inflammatory response following repetitive, intrathecally administered antisense oligonucleotides (ASO) in 5q-associated spinal muscular atrophy (SMA) are sparse. Increased risk of hydrocephalus in untreated SMA patients and a marginal but significant increase of the serum/CSF albumin ratio (Qalb) with rare cases of communicating hydrocephalus during nusinersen treatment were reported, which confirms the unmet need of an inflammatory biomarker in SMA. The aim of this study was to investigate the (neuro)inflammatory marker chitotriosidase 1 (CHIT1) in SMA patients before and following the treatment with the ASO nusinersen.

Methods

In this prospective, multicenter observational study, we studied CSF CHIT1 concentrations in 58 adult and 21 pediatric patients with SMA type 1, 2 or 3 before treatment initiation in comparison to age- and sex-matched controls and investigated its dynamics during nusinersen treatment. Concurrently, motor performance and disease severity were assessed.

Results

CHIT1 concentrations were elevated in treatment-naïve SMA patients as compared to controls, but less pronounced than described for other neurodegenerative diseases such as amyotrophic lateral sclerosis. CHIT1 concentration did not correlate with disease severity and did not distinguish between clinical subtypes. CHIT1 concentration did show a significant increase during nusinersen treatment that was unrelated to the clinical response to nusinersen therapy.

Conclusions

CHIT1 elevation in treatment-naïve SMA patients indicates the involvement of (neuro)inflammation in SMA. The lacking correlation of CHIT1 concentration with disease severity argues against its use as a marker of disease progression. The observed CHIT1 increase during nusinersen treatment may indicate an immune response-like, off-target reaction. Since antisense oligonucleotides are an establishing approach in the treatment of neurodegenerative diseases, this observation needs to be further evaluated.
Intensive care–treated cardiac arrest: a retrospective study on the impact of extended age on mortality, neurological outcome, received treatments and healthcare-associated costs
Authors: Holmström Ester , Efendijev Ilmar , Raj Rahul , Pekkarinen Pirkka T. , Litonius Erik , Skrifvars Markus B.
Published: July 2021

Background

Cardiac arrest (CA) is a leading cause of death worldwide. As population ages, the need for research focusing on CA in elderly increases. This study investigated treatment intensity, 12-month neurological outcome, mortality and healthcare-associated costs for patients aged over 75 years treated for CA in an intensive care unit (ICU) of a tertiary hospital.

Methods

This single-centre retrospective study included adult CA patients treated in a Finnish tertiary hospital’s ICU between 2005 and 2013. We stratified the study population into two age groups: <75 and $$\ge$$
≥
75 years. We compared interventions defined by the median daily therapeutic scoring system (TISS-76) between the age groups to find differences in treatment intensity. We calculated cost-effectiveness by dividing the total one-year healthcare-associated costs of all patients by the number of survivors with a favourable neurological outcome. Favourable outcome was defined as a cerebral performance category (CPC) of 1–2 at 12 months after cardiac arrest. Logistic regression analysis was used to identify independent associations between age group, mortality and neurological outcome.

Results

This study included a total of 1,285 patients, of which 212 (16 %) were $$\ge$$
≥
75 years of age. Treatment intensity was lower for the elderly compared to the younger group, with median TISS scores of 116 and 147, respectively (p < 0.001). The effective cost in euros for patients with a good one-year neurological outcome was €168,000 for the elderly and €120,000 for the younger group. At 12 months after CA 24 % of the patients in the elderly group and 47 % of the patients in the younger group had a CPC of 1–2 (p < 0.001). Age was an independent predictor of mortality (multivariate OR = 2.90, 95 % CI: 1.94–4.31, p < 0.001) and neurological outcome (multivariate OR = 3.15, 95 % CI: 2.04–4.86, p < 0.001).

Conclusions

The elderly ICU-treated CA patients in this study had worse neurological outcomes, higher mortality and lower cost-effectiveness than younger patients. Elderly received less intense treatment. Further efforts are needed to recognize the tools for assessing which elderly patients benefit from a more aggressive treatment approach in order to improve the cost-effectiveness of post-CA management.
A multiplex PCR assay for six Aedini species, including Aedes albopictus
Authors: Bang Woo Jun , Won Min Hyeok , Cho Seong Tae , Ryu Jihun , Choi Kwang Shik
Published: July 2021

Background

Mosquitoes, as vectors of various human pathogens, are significant drivers of serious human illness. In particular, those species in the Aedini tribe, which typically transmit dengue virus, Chikungunya fever virus, and Zika virus, are increasing their range because of climate change and international commerce. In order to evaluate the risk of disease transmission, accurate mosquito species identification and monitoring are needed. The goal of this work was to develop a rapid and simple molecular diagnostic method for six morphologically similar Aedini species (Aedes flavopictus, Aedes albopictus, Ochlerotatus koreicus, Ochlerotatus japonicus, Ochlerotatus togoi and Ochlerotatus hatorii) in Korea.

Methods

A total of 109 samples were assayed in this study. The internal transcribed spacer 2 (ITS2) regions from all six species were amplified, sequenced and analyzed using Mega 6. Following the identification of regions that were consistently different in terms of sequence between all six species, multiplex primers were designed to amplify these regions to generate species-specific fragments distinguishable by their size.

Results

Uniquely sized fragments were generated in Ae. flavopictus (495 bp), Ae. albopictus (438 bp), Oc. koreicus (361 bp), Oc. togoi (283 bp), Oc. hatorii (220 bp) and Oc. japonicus (160 bp). Pairwise distance analysis showed that the difference was 35.0 ± 1.5% between Aedes spp. and Ochlerotatus spp., 17.4 ± 0.2% between Ae. albopictus and Ae. flavopictus and 11.1 ± 0.3% between Oc. koreicus and Oc. japonicus.

Conclusions

In this study, a multiplex PCR assay for six species of the Aedini tribe was developed. This assay is more accurate than morphological identification and will be useful for monitoring and controlling these vector mosquitoes.

Graphical Abstract
Aedes aegypti continuously exposed to Bacillus thuringiensis svar. israelensis does not exhibit changes in life traits but displays increased susceptibility for Zika virus
Authors: Carvalho Karine da Silva , Guedes Duschinka Ribeiro Duarte , Crespo Mônica Maria , de Melo-Santos Maria Alice Varjal , Silva-Filha Maria Helena Neves Lobo
Published: July 2021

Background

Aedes aegypti can transmit arboviruses worldwide, and Bacillus thuringiensis svar. israelensis (Bti)-based larvicides represent an effective tool for controlling this species. The safety of Bti and lack of resistance have been widely reported; however, little is known regarding the impact of the extensive use of these larvicides on the life traits of mosquitoes. Therefore, this study investigated biological parameters, including susceptibility to arbovirus, of an Ae. aegypti strain (RecBti) subjected to 29 generations of exposure to Bti compared with the RecL reference strain.

Methods

The biological parameters of individuals reared under controlled conditions were compared. Also, the viral susceptibility of females not exposed to Bti during their larval stage was analysed by oral infection and followed until 14 or 21 days post-infection (dpi).

Results

RecBti individuals did not display alterations in the traits that were assessed (fecundity, fertility, pupal weight, developmental time, emergence rate, sex ratio and haematophagic capacity) compared to RecL individuals. Females from both strains were susceptible to dengue serotype 2 (DENV-2) and Zika virus (ZIKV). However, RecBti females showed significantly higher rates of ZIKV infection compared with RecL females at 7 (90% versus 68%, Chi-square: χ2 = 7.27, df = 1, P = 0.006) and 14 dpi (100% versus 87%, Chi-square: χ2 = 7.69, df = 1, P = 0.005) and for dissemination at 7 dpi (83.3% versus 36%, Fisher’s exact test: P < 0.0001, OR = 0.11, 95% CI 0.03–0.32). Quantification of DENV-2 and ZIKV viral particles produced statistically similar results for females from both strains.

Conclusions

Prolonged exposure of Ae. aegypti larvae to Bti did not alter most of the evaluated biological parameters, except that RecBti females exhibited a higher vector susceptibility for ZIKV. This finding is related to a background of Bti exposure for several generations but not to a previous exposure of the tested females during the larval stage. This study highlights mosquito responses that could be associated with the chronic exposure to Bti in addition to the primary larvicidal effect elicited by this control agent.

Graphical abstract
Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage
Authors: Meyer Douglas , Kames Jacob , Bar Haim , Komar Anton A. , Alexaki Aikaterini , Ibla Juan , Hunt Ryan C. , Santana-Quintero Luis V. , Golikov Anton , DiCuccio Michael , Kimchi-Sarfaty Chava
Published: July 2021

Background

Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.

Methods

We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.

Results

We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.

Conclusions

Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available athttps://dnahive.fda.gov/review/cancercocoputs/. These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.
Urate-induced epigenetic modifications in myeloid cells
Authors: Badii M. , Gaal O. I. , Cleophas M. C. , Klück V. , Davar R. , Habibi E. , Keating S. T. , Novakovic B. , Helsen M. M. , Dalbeth N. , Stamp L. K. , Macartney-Coxson D. , Phipps-Green A. J. , Stunnenberg H. G. , Dinarello C. A. , Merriman T. R. , Netea M. G. , Crişan T. O. , Joosten L. A. B.
Published: July 2021

Objectives

Hyperuricemia is a metabolic condition central to gout pathogenesis. Urate exposure primes human monocytes towards a higher capacity to produce and release IL-1β. In this study, we assessed the epigenetic processes associated to urate-mediated hyper-responsiveness.

Methods

Freshly isolated human peripheral blood mononuclear cells or enriched monocytes were pre-treated with solubilized urate and stimulated with LPS with or without monosodium urate (MSU) crystals. Cytokine production was determined by ELISA. Histone epigenetic marks were assessed by sequencing immunoprecipitated chromatin. Mice were injected intraarticularly with MSU crystals and palmitate after inhibition of uricase and urate administration in the presence or absence of methylthioadenosine. DNA methylation was assessed by methylation array in whole blood of 76 participants with normouricemia or hyperuricemia.

Results

High concentrations of urate enhanced the inflammatory response in vitro in human cells and in vivo in mice, and broad-spectrum methylation inhibitors reversed this effect. Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 27 acetylation (H3K27ac) revealed differences in urate-primed monocytes compared to controls. Differentially methylated regions (e.g. HLA-G, IFITM3, PRKAB2) were found in people with hyperuricemia compared to normouricemia in genes relevant for inflammatory cytokine signaling.

Conclusion

Urate alters the epigenetic landscape in selected human monocytes or whole blood of people with hyperuricemia compared to normouricemia. Both histone modifications and DNA methylation show differences depending on urate exposure. Subject to replication and validation, epigenetic changes in myeloid cells may be a therapeutic target in gout.
Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy
Authors: Maredia Ashna , Guzzardi David , Aleinati Mohammad , Iqbal Fatima , Khaira Arshroop , Madhu Aiswarya , Wang Xuemei , Barker Alex J. , McCarthy Patrick M. , Fedak Paul W. M. , Greenway Steven C.
Published: July 2021

Background

The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy.

Methods

We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death.

Results

Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter.

Conclusions

In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.
Hepatic inflammatory pseudotumor-like follicular dendritic cell tumor: a case report
Authors: Pascariu Ana Daniela , Neagu Andreea Ioana , Neagu Andrei Valentin , Băjenaru Alexandru , Bețianu Cezar Iulian
Published: July 2021

Background

Inflammatory pseudotumor-like follicular dendritic cell sarcoma is a rare histological variant of follicular dendritic cell sarcoma involving typically the spleen and the liver, often linked to the presence of Epstein–Barr virus infection. Definite diagnosis of this type of sarcoma is difficult to make owing to nonspecific clinical and imaging findings and is based on histopathological features. Inflammatory pseudotumor-like follicular dendritic cell sarcoma is described as a low-aggressivity tumor with a favorable prognosis.

Case presentation

We report the case of a 34-year-old Caucasian woman, Epstein–Barr virus positive, diagnosed with hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma and surgically treated in November 2014, who developed 6 years later a recurrence for which she underwent once again surgical treatment. As far as we know, fewer than 30 reports of inflammatory pseudotumor-like follicular dendritic cell liver tumors have been reported in the English literature.

Conclusions

Although it is an uncommon tumor, inflammatory pseudotumor-like sarcoma is a diagnostic worth being taken in consideration, and surveillance is recommended owing to the possibility of recurrence.
Hypoglycemia as a cause of sudden cardiac arrest during cesarean delivery under spinal anesthesia: a case report and review of the literature
Authors: Tilahun Temesgen , Gudina Guteta
Published: July 2021

Background

Sudden cardiac arrest during spinal anesthesia is a rare event. However, its management by an unprepared team is difficult and carries poor outcomes. Hypoglycemia as the cause of sudden cardiac arrest is rarely reported. This case illustrates lifesaving procedures for sudden cardiac arrest secondary to hypoglycemia during cesarean delivery under spinal anesthesia.

Case summary

We report a case, from rural Ethiopia of sudden cardiac arrest secondary to hypoglycemia during cesarean delivery under spinal anesthesia. The case was successfully managed by a team of anesthetists and other operating teams. The mother and newborn were discharged from the hospital on the 7th postoperative day.

Conclusion

Hypoglycemia during cesarean delivery under spinal anesthesia can cause sudden cardiac arrest. Therefore, identifying patients at risk of developing hypoglycemia, monitoring the patient’s condition, and initiating prompt intervention at the first sign of cardiovascular instability is advisable. Determining serum blood glucose levels at admission to the labor ward and monitoring blood glucose levels during spinal anesthesia should be routine practices.
Mkx mediates tenogenic differentiation but incompletely inhibits the proliferation of hypoxic MSCs
Authors: Chen Guanyin , Fan Dong , Zhang Wangqian , Wang Shuning , Gu Jintao , Gao Yuan , He Lei , Li Weina , Zhang Cun , Li Meng , Zhang Yingqi , Liu Zhaohui , Hao Qiang
Published: July 2021

Background

Hypoxia has been shown to be able to induce tenogenic differentiation and proliferation of mesenchymal stem cells (MSCs) which lead hypoxia-induced MSCs to be a potential treatment for tendon injury. However, little is known about the mechanism underlying the tenogenic differentiation and proliferation process of hypoxic MSCs, which limited the application of differentiation-inducing therapies in tendon repair. This study was designed to investigate the role of Mohawk homeobox (Mkx) in tenogenic differentiation and proliferation of hypoxic MSCs.

Methods

qRT-PCR, western blot, and immunofluorescence staining were performed to evaluate the expression of Mkx and other tendon-associated markers in adipose-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) under hypoxia condition. Small interfering RNA technique was applied to observe the effect of Mkx levels on the expression of tendon-associated markers in normoxic and hypoxic BMSCs. Hypoxic BMSCs infected with Mkx-specific short hair RNA (shRNA) or scramble were implanted into the wound gaps of injured patellar tendons to assess the effect of Mkx levels on tendon repair. In addition, cell counting kit-8 assay, colony formation unit assay, cell cycle analysis, and EdU assay were adopted to determine the proliferation capacity of normoxic or hypoxic BMSCs infected with or without Mkx-specific shRNA.

Results

Our data showed that the expression of Mkx significantly increased in hypoxic AMSCs and increased much higher in hypoxic BMSCs. Our results also detected that the expression of tenogenic differentiation markers after downregulation of Mkx were significantly decreased not only in normoxic BMSCs, but also in hypoxic BMSCs which paralleled the inferior histological evidences, worse biomechanical properties, and smaller diameters of collagen fibrils in vivo. In addition, our in vitro data demonstrated that the optical density values, the clone numbers, the percentage of cells in S phage, and cell proliferation potential of both normoxic and hypoxic BMSCs were all significantly increased after knockdown of Mkx and were also significantly enhanced in both AMSCs and BMSCs in hypoxia condition under which the expression of Mkx was upregulated.

Conclusions

These findings strongly suggested that Mkx mediated hypoxia-induced tenogenic differentiation of MSCs but could not completely repress the proliferation of hypoxic MSCs.
Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model
Authors: Duan Ao , Shen Kai , Li Beichen , Li Cong , Zhou Hao , Kong Renyi , Shao Yuqi , Qin Jian , Yuan Tangbo , Ji Juan , Guo Wei , Wang Xipeng , Xue Tengfei , Li Lei , Huang Xinxin , Sun Yuqin , Cai Zhenyu , Liu Wei , Liu Feng
Published: July 2021

Background

Previous studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA). This study sought to explore effects of LPS-pre EVs on chondrocyte proliferation, migration, and chondrocyte apoptosis, as well as the protective effect of LPS-pre EVs on mouse articular cartilage.

Methods

Chondrocytes were extracted to explore the effect of LPS-pre EVs on proliferation, migration, and apoptosis of chondrocytes. In addition, the effect of LPS-pre EVs on expression level of important proteins of chondrocytes was explored suing in vitro experiments. Further, intraarticular injection of LPS-pre EVs was performed on the destabilization of the medial meniscus (DMM)-induced mouse models of OA to explore the therapeutic effect of LPS-pre EVs on osteoarthritis in vivo.

Results

Analysis showed that LPS-pre EVs significantly promoted proliferation and migration of chondrocytes and inhibited the apoptosis of chondrocytes compared with PBS and EVs. Moreover, LPS-pre EVs inhibited decrease of aggrecan and COL2A1 and increase of ADAMTS5 caused by IL-1β through let-7b. Furthermore, LPS-pre EVs significantly prevented development of OA in DMM-induced mouse models of OA.

Conclusions

LPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.
Sexual dimorphism of monocyte transcriptome in individuals with chronic low-grade inflammation
Authors: So Jisun , Tai Albert K. , Lichtenstein Alice H. , Wu Dayong , Lamon-Fava Stefania
Published: July 2021

Sexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjustedpvalue (FDR) < 0.1], including genes involved in immune cell activation (e.g.,CEACAM1,FCGR2B, andSLAMF7) and antigen presentation (e.g.,AIM2,CD1E, andUBA1) with a higher expression in females than males. Moreover, signaling pathways of immune or inflammatory responses, including interferon (IFN) signaling [z-score = 2.45, -log(p) = 3.88], were found to be more upregulated in female versus male monocytes, based on a set of genes exhibiting sex-biased expression (p< 0.03). The contribution of IFN signaling to the sexual transcriptional differences was further confirmed by direct comparisons of the monocyte sex-biased genes with IFN signature genes (ISGs) that were previously curated in mouse macrophages. ISGs showed a greater overlap with female-biased genes than male-biased genes and a higher overall expression in female than male monocytes, particularly for the genes of antiviral and inflammatory responses to IFN. Given the role of IFN in immune defense and autoimmunity, our results suggest that sexual dimorphism in immune functions may be associated with more priming of innate immune pathways in female than male monocytes. These findings highlight the role of sex on the human immune transcriptome.
Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease
Authors: Zhang Yujue , Fan Yuanyuan , He Wei , Han Yi , Bao Huarui , Yang Renjun , Wang Bingbing , Kong Derun , Wang Hua
Published: July 2021

Background

Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear.

Results

In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8.

Conclusions

Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.
Results on fixed circles and discs for $L_{ (\omega,C ) }$-contractions and related applications
Authors: Ameer Eskandar , Aydi Hassen , Nazam Muhammad , De la Sen Manuel
Published: July 2021

In this paper, we study the behavior of $L_{ ( \omega,C ) }$

L

(
ω
,
C
)

-contraction mappings and establish some results on common fixed circles and discs. We explain the significance of our main theorems through examples and applications.
Effectiveness of mycofiltration for removal of contaminants from water: a systematic review protocol
Authors: Mnkandla Sanele Michelle , Otomo Patricks Voua
Published: July 2021

Background

Mycofiltration is an environment friendly technology which involves the treatment of contaminated water by passing it through a network of fungal mycelium. This technology has gained momentum over the years, and the systematic review chartered in this protocol will compile and synthesise literature on mycofiltration studies, paying special attention to the types and levels of contaminants removed. The systematic review should provide insight into the removal efficiency of mycofiltration by synthesising the mycofiltration knowledge base. Moreover, the proposed contribution will inform further research and provide comprehensive information to relevant stakeholders, such as municipalities, which might be in need of interventions for alleviating wastewater-related pollution in surrounding water bodies.

Methods

This systematic review protocol is based on the question, “What is the effectiveness of mycofiltration for removal of contaminants from water?” A thorough search of peer reviewed journal articles and grey literature sources will be conducted on academic journal databases, websites, specialist sources such as environmental organisations as well social and networking sources. A supplemental search will also be performed by forward and backward citation tracing. A two-stage screening process at title, abstract and full text level, will be conducted, against predefined inclusion criteria. Studies that meet inclusion criteria will be subjected to quality assessment. Data will be extracted and compiled into a narrative synthesis and summarised into tables and figures. Meta-analysis will be performed where sufficient evidence-base allows.
Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson’s disease
Authors: He Shulei , Huang Lu , Shao Ci , Nie Tiejian , Xia Li , Cui Bozhou , Lu Fangfang , Zhu Lin , Chen Bolin , Yang Qian
Published: July 2021

Background

Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD.

Methods

A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants.

Results

WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD.

Conclusions

The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.
Risk assessment of soil erosion by using CORINE model in the western part of Syrian Arab Republic
Authors: Khallouf Alaa , Talukdar Swapan , Harsányi Endre , Abdo Hazem Ghassan , Mohammed Safwan
Published: July 2021

Background

Soil erosion is a major threat to the natural ecosystem and agricultural sector in the western part of Lattakia Governorate, Syrian Arab Republic. The main goals of this research are to investigate erosion risk by using the Coordination of Information on the Environment (CORINE) Model and to prioritize areas for conservation practices. To achieve these goals, soil samples were collected from the field, the climatic data (i.e., rainfall) and Digital Elevation Model (DEM) were obtained and utilized to perform CORINE model in Geographic Information System (GIS) environment.

Results

The results showed that only 13.2% of the study area was classified as high erodible. In addition, 45.24%, 49.15% and 5.29% of the study area were under low, moderate and high actual erosion risk, respectively. This research identified slope and land use/land cover as key factors responsible for soil erosion in the study area.

Conclusions

The CORINE model acknowledged as a good tool for predicting soil erosion and highlighting the areas affected by soil erosion in the study area with high precision.
A comprehensive analysis of copy number variation in a Turkish dementia cohort
Authors: Dehghani Nadia , Guven Gamze , Kun-Rodrigues Celia , Gouveia Catarina , Foster Kalina , Hanagasi Hasmet , Lohmann Ebba , Samanci Bedia , Gurvit Hakan , Bilgic Basar , Bras Jose , Guerreiro Rita
Published: July 2021

Background

Copy number variants (CNVs) include deletions or multiplications spanning genomic regions. These regions vary in size and may span genes known to play a role in human diseases. As examples, duplications and triplications ofSNCAhave been shown to cause forms of Parkinson’s disease, while duplications ofAPPcause early onset Alzheimer’s disease (AD).

Results

Here, we performed a systematic analysis of CNVs in a Turkish dementia cohort in order to further characterize the genetic causes of dementia in this population. One hundred twenty-four Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD, or frontotemporal dementia, were whole-genome genotyped and CNVs were detected. We integrated family analysis with a comprehensive assessment of potentially disease-associated CNVs in this Turkish dementia cohort. We also utilized both dementia and non-dementia individuals from the UK Biobank in order to further elucidate the potential role of the identified CNVs in neurodegenerative diseases.

We report CNVs overlapping the previously implicated genesZNF804A, SNORA70B, USP34, XPO1, and a locus on chromosome 9 which includes a cluster of olfactory receptors andABCA1. Additionally, we also describe novel CNVs potentially associated with dementia, overlapping the genesAFG1L, SNX3, VWDE, andBC039545.

Conclusions

Genotyping data from understudied populations can be utilized to identify copy number variation which may contribute to dementia.
Biomarkers and cell-based models to predict the outcome of neoadjuvant therapy for rectal cancer patients
Authors: Alkan Aylin , Hofving Tobias , Angenete Eva , Yrlid Ulf
Published: July 2021

Rectal cancer constitutes approximately one-third of all colorectal cancers and contributes to considerable mortality globally. In contrast to colon cancer, the standard treatment for localized rectal cancer often involves neoadjuvant chemoradiotherapy. Tumour response rates to treatment show substantial inter-patient heterogeneity, indicating a need for treatment stratification. Consequently researchers have attempted to establish new means for predicting tumour response in order to assist in treatment decisions. In this review we have summarized published findings regarding potential biomarkers to predict neoadjuvant treatment response for rectal cancer tumours. In addition, we describe cell-based models that can be utilized both for treatment prediction and for studying the complex mechanisms involved.