bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of biological correlates associated with respiratory failure in COVID-19
Authors: Oh Jung Hun , Tannenbaum Allen , Deasy Joseph O.
Published: December 2020

Background

Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group.

Methods

Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients.

Results

We considered the top 708 SNPs, using a p-value cutoff of 5 × 10− 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases.

Conclusion

Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.
Bone marrow mesenchymal stem cells derived miRNA-130b enhances epithelial sodium channel by targeting PTEN
Authors: Zhang Honglei , Ding Yan , Hou Yapeng , Liu Yanhong , Zhou Zhiyu , Nie Hongguang
Published: December 2020

Aims

Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality, and severe pulmonary edema is one of the characteristics. Epithelial sodium channel (ENaC) located on the apical side of alveolar type 2 epithelial (AT2) cells is the primary rate limiting segment in alveolar fluid clearance. Many preclinical studies have revealed that mesenchymal stem cells (MSCs) based therapy has great therapeutic potential for ALI, while the role of ENaC in this process is rarely known.

Methods

We studied the effects of bone marrow-derived MSCs (BMSCs) on the protein/mRNA expression and activity of ENaC in primary mouse AT2 and human H441 cells by co-culture with them, respectively. Moreover, the changes of miRNA-130b in AT2 cells were detected by qRT-PCR, and we studied the involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and the downstream PI3K/AKT pathway in the miRNA-130b regulation of ENaC.

Results

Our results demonstrated that BMSCs could increase ENaC protein expression and function, as well as the expression level of miRNA-130b. The dual luciferase target gene assay verified that PTEN was one of the target genes of miR-130b, which showed adverse effects on the protein expression of α/γ-ENaC and PTEN in AT2 cells. Upregulating miR-130b and/or knocking down PTEN resulted in the increase of α/γ-ENaC protein level, and the protein expression of p-AKT/AKT was enhanced by miR-130b. Both α and γ-ENaC protein expressions were increased after AT2 cells were transfected with siPTEN, which could be reversed by the co-administration of PI3K/AKT inhibitor LY294002.

Conclusion

In summary, miRNA-130b in BMSCs can enhance ENaC at least partially by targeting PTEN and activating PI3K/AKT pathway, which may provide a promising new direction for therapeutic strategy in ALI.
Health-related quality of life in nonvalvular atrial fibrillation patients with controlled or uncontrolled anticoagulation status
Authors: Varona José Felipe , Seguí-Ripoll José Miguel , Lozano-Duran Cristina , Cuadrado-Gómez Luis Miguel , Montagud-Moncho Juan Bautista , Ramos-Guerrero Antonio , Mirete-Ferrer José Carlos , Donado Esther , García-Alegría Javier ,   the REQUOL Study Group
Published: December 2020

Background

There is a dearth of evidence regarding Health-Related Quality of Life (HRQoL) in nonvalvular atrial fibrillation (NVAF) patients undergoing oral anticoagulation therapy. Our objective was to describe HRQoL in NVAF patients on oral anticoagulation, focusing on uncontrolled patients on vitamin K antagonists (VKAs) versus controlled patients on VKAs or non-vitamin K antagonist oral anticoagulants (NOACs), in a real-world setting. Additionally, we assessed the clinical characteristics of patients with uncontrolled anticoagulation.

Methods

An observational, multicentre, and cross-sectional study, enrolling 38 Spanish Hospitals' Internal Medicine Departments. HRQoL was assessed using the validated Spanish version of the Sawicki questionnaire. High self-perceived HRQoL was indicated by high scores in the general treatment satisfaction and self-efficacy dimensions, and by low scores in the strained social network, daily hassles and distress dimensions.

Results

Five hundred and one patients were included for assessment. Mean scores ± SD were closer to a high perceived HRQoL in controlled than uncontrolled patients for the five dimensions of the questionnaire: 4.9 ± 1.0 versus 3.6 ± 1.3 for general treatment satisfaction; 4.3 ± 1.0 versus 3.6 ± 1.0 for self-efficacy, 3.1 ± 0.9 versus 3.9 ± 1.1 for strained social network, 2.1 ± 0.8 versus 3.0 ± 1.0 for daily hassles and 1.8 ± 0.9 versus 2.6 ± 1.2 for distress.

Conclusions

HRQoL in patients with controlled anticoagulant status treated with NOACs or VKAs was better than in patients with uncontrolled anticoagulant status. This seems to indicate that anticoagulation control status influences perception of HRQoL, highlighting the importance of its evaluation when assessing HRQoL in NVAF patients.
Induction chemotherapy for the individualised treatment of hypopharyngeal carcinoma with cervical oesophageal invasion: a retrospective cohort study
Authors: Huang Tian-Qiao , Wang Ru , Fang Ju-Gao , He Shi-Zhi , Zhong Qi , Hou Li-Zhen , Ma Hong-Zhi , Chen Xiao-Hong , Chen Xue-Jun , Li Ping-Dong , Feng Ling , Shi Qian , Lian Meng
Published: December 2020

Background

This study aimed to evaluate the potential of induction chemotherapy as an indicator of the management of advanced hypopharyngeal carcinoma with cervical oesophageal invasion.

Methods

Sixty-eight patients admitted to our hospital between February 2003 and November 2016 with stage IVB hypopharyngeal carcinoma with cervical oesophageal invasion were retrospectively analysed. Patients were divided into two groups according to the treatment they selected following an explanation of the different treatments available. Patients in group A received induction chemotherapy and had (1) complete/partial remission following chemotherapy and radiotherapy/concurrent chemoradiotherapy or (2) stable disease following chemotherapy and surgery. Patients in group B underwent surgery followed by adjuvant radiotherapy/concurrent chemoradiotherapy. Survival analyses were performed using the Kaplan–Meier method, and differences between the groups were evaluated using the log-rank test. Laryngeal and oesophageal retention rates were compared using the cross-tabulation test.

Results

The 3- and 5-year overall survival rates were 22.86% and 11.43% in group A and 24.25% and 6.06% in group B, respectively (all P > 0.05). The laryngeal and oesophageal retention rates were 40.0% and 74.3% in group A and 0.0% and 27.3% in group B, respectively (all P < 0.01). There was no statistically significant difference in the incidence of post-operative complications between the two groups (group A 8.6%, group B 12.1%; P > 0.05).

Conclusions

Induction chemotherapy may be an appropriate first choice to ensure laryngeal and oesophageal preservation in the individualised treatment of advanced hypopharyngeal carcinoma with cervical oesophageal invasion.
Primary endometrioid carcinoma of the uterosacral ligament arising from deep infiltrating endometriosis 6 years after bilateral salpingo-oophorectomy due to atypical proliferative endometrioid tumor of the ovary: a rare case report
Authors: Ota Yoshiaki , Ota Kuniaki , Takahashi Toshifumi , Suzki Soichiro , Sano Rikiya , Ota Ikuko , Moriya Takuya , Shiota Mitsuru
Published: December 2020

Background

Endometriosis can potentially lead to the development of a malignant tumor. Most malignant tumors arising from the endometriosis originate from the ovarian endometrioma, whereas those arising from extragonadal lesions are rare. We report a rare case of endometrioid carcinoma that developed from deep infiltrating endometriosis in the uterosacral ligament 6 years after treatment for atypical proliferative endometrioid tumor of the ovary in a 48-year-old woman.

Case presentation

Six years ago, the patient underwent laparoscopic bilateral salpingo-oophorectomy for her right ovarian tumor with atypical proliferative (borderline) endometrioid tumor accompanied by ovarian endometrioma. The solid tumor in the cul-de-sac was detected during follow-up using magnetic resonance imaging. Positron emission tomography/computed tomography revealed an abnormal accumulation of 18F-fluorodeoxyglucose at the tumor site. Thus, tumor recurrence with borderline malignancy was suspected. The patient underwent diagnostic laparoscopy followed by hysterectomy and partial omentectomy. Retroperitoneal pelvic lymphadenectomy and para-aortic lymphadenectomy were also performed. The cul-de-sac tumor at the left uterosacral ligament was microscopically diagnosed as invasive endometrioid carcinoma arising from deep infiltrating endometriosis. The final diagnosis was primary stage IIB peritoneal carcinoma. The patient received six courses of monthly paclitaxel and carboplatin as adjuvant chemotherapy. The patient showed no evidence of recurrence for 2 years after the treatments.

Conclusion

This study reports a rare case of metachronous endometriosis-related malignancy that developed 6 years after treatment for borderline ovarian tumor. If endometriosis lesions remain after bilateral salpingo-oophorectomy, the physician should keep the malignant nature of endometriosis in mind.
Genipin improves reproductive health problems caused by circadian disruption in male mice
Authors: Xu Yihua , Wang Li , Cao Siyuan , Hu Ruihua , Liu Rui , Hua Ke , Guo Zhigang , Di Hong-Jie , Hu Zhigang
Published: December 2020

Background

Circadian rhythm disruption impacts a wide range of physiological processes, including fertility. However, the effect of circadian disruption on male spermatogenesis and fertility, and treatments for these effects have been largely unexplored at the molecular level.

Methods

In this study, we examined the effects of genipin on improving the reproductive health problems caused by circadian disruption. Three groups of animals were fed under different conditions: control group (normal T cycle with saline), group of shortened T cycles (Light/Dark = 4 hours/4 hours) with saline, and a group of shortened T cycles with genipin by oral gavage. The male fertility was evaluated by fertility study and pups parameters analysis after successful sexual behavior and mating with female mice. We sacrificed the treated animals after 5 or 10 weeks and collected the testis, sperm and serum for histological analysis, sperm motility assay, and serum hormone detection, respectively. Furthermore, the effect of genipin was assessed by detection of progesterone secretion and steroidogenic key proteins expression, including StAR and CYP11A1, in mouse Leydig tumor MLTC-1 cells.

Results

Male mice exposed to shortened light-dark cycles, much shorter than 24 hours, had reduced fertility with decreased sperm concentrations and sperm motility. Male mice under circadian disruption have reduced testis size and abnormal morphology, leading to lower fertility rates, reduced litter size and pup body weight. Treatment with exogenous genipin, a natural plant-derived compound, alleviated circadian disruption-induced damage to fertility and spermatogenesis and normalized testosterone, dihydrotestosterone (DHT), and androstenedione (ASD) levels in the male mice. The levels of key proteins involved in steroidogenesis, StAR and CYP11A1, were reduced in mouse testes after the circadian disruption, but genipin treatment restored the reduction. The mRNA expression of SRD5A1, which encodes an androgen synthesis enzyme, was also upregulated by genipin treatment. Furthermore, genipin treatment showed a positive effect on steroidogenesis in MLTC-1 cells, resulting in an increase in hormone secretion and the upregulation of StAR and CYP11A1.

Conclusions

Our results showed an association between circadian disruption and reproductive health problems in male mice and indicated that treatments with genipin have positive effects on the reproductive health of male mice with circadian rhythm disorders.
PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer
Authors: Wei Xiao-Li , Luo Xuan , Sheng Hui , Wang Yun , Chen Dong-Liang , Li Jia-Ning , Wang Feng-Hua , Xu Rui-Hua
Published: December 2020

Background

The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.

Methods

74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity.

Results

The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03–0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases.

Conclusions

The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.
The roles of osteocytes in alveolar bone destruction in periodontitis
Authors: Huang Xiaofei , Xie Mengru , Xie Yanling , Mei Feng , Lu Xiaofeng , Li Xiaoshuang , Chen Lili
Published: December 2020

Periodontitis, a bacterium-induced inflammatory disease that is characterized by alveolar bone loss, is highly prevalent worldwide. Elucidating the underlying mechanisms of alveolar bone loss in periodontitis is crucial for understanding its pathogenesis. Classically, bone cells, such as osteoclasts, osteoblasts and bone marrow stromal cells, are thought to dominate the development of bone destruction in periodontitis. Recently, osteocytes, the cells embedded in the mineral matrix, have gained attention. This review demonstrates the key contributing role of osteocytes in periodontitis, especially in alveolar bone loss. Osteocytes not only initiate physiological bone remodeling but also assist in inflammation-related changes in bone remodeling. The latest evidence suggests that osteocytes are involved in regulating bone anabolism and catabolism in the progression of periodontitis. The altered secretion of receptor activator of NF-κB ligand (RANKL), sclerostin and Dickkopf-related protein 1 (DKK1) by osteocytes affects the balance of bone resorption and formation and promotes bone loss. In addition, the accumulation of prematurely senescent and apoptotic osteocytes observed in alveolar bone may exacerbate local destruction. Based on their communication with the bloodstream, it is noteworthy that osteocytes may participate in the interaction between local periodontitis lesions and systemic diseases. Overall, further investigations of osteocytes may provide vital insights that improve our understanding of the pathophysiology of periodontitis.
Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlie differences in modulation of in vitro myelination
Authors: Werkman Inge L. , Dubbelaar Marissa L. , van der Vlies Pieter , de Boer-Bergsma Jelkje J. , Eggen Bart J. L. , Baron Wia
Published: December 2020

Background

Multiple sclerosis (MS) is an inflammation-mediated demyelinating disease of the central nervous system that eventually results in secondary axonal degeneration due to remyelination failure. Successful remyelination is orchestrated by astrocytes (ASTRs) and requires sequential activation, recruitment, and maturation of oligodendrocyte progenitor cells (OPCs). In both MS and experimental models, remyelination is more robust in grey matter (GM) than white matter (WM), which is likely related to local differences between GM and WM lesions. Here, we investigated whether adult gmASTRs and wmASTRs per se and in response to MS relevant Toll-like receptor (TLR) activation differently modulate myelination.

Methods

Differences in modulation of myelination between adult gmASTRs and wmASTRs were examined using an in vitro myelinating system that relies on a feeding layer of ASTRs. Transcriptional profiling and weighted gene co-expression network analysis were used to analyze differentially expressed genes and gene networks. Potential differential modulation of OPC proliferation and maturation by untreated adult gmASTRs and wmASTRs and in response to TLR3 and TLR4 agonists were assessed.

Results

Our data reveal that adult wmASTRs are less supportive to in vitro myelination than gmASTRs. WmASTRs more abundantly express reactive ASTR genes and genes of a neurotoxic subtype of ASTRs, while gmASTRs have more neuro-reparative transcripts. We identified a gene network module containing cholesterol biosynthesis enzyme genes that positively correlated with gmASTRs, and a network module containing extracellular matrix-related genes that positively correlated with wmASTRs. Adult wmASTRs and gmASTRs responding to TLR3 agonist Poly(I:C) distinctly modulate OPC behavior, while exposure to TLR4 agonist LPS of both gmASTRs and wmASTRs results in a prominent decrease in myelin membrane formation.

Conclusions

Primary adult gmASTRs and wmASTRs are heterogeneous at the transcriptional level, differed in their support of in vitro myelination, and their pre-existing phenotype determined TLR3 agonist responses. These findings point to a role of ASTR heterogeneity in regional differences in remyelination efficiency between GM and WM lesions.
Does tourniquet use affect the periprosthetic bone cement penetration in total knee arthroplasty? A meta-analysis
Authors: Lu Chao , Song Min , Chen Jin , Li Congcong , Lin Wenzheng , Ye Guozhu , Wu Gaoyi , Li Anan , Cai Yuning , Wu Huai , Liu Wengang , Xu Xuemeng
Published: December 2020

Background

A tourniquet is a device commonly used to control massive hemorrhage during knee replacement surgery. However, the question remains whether the use of tourniquets affects the permeability of the bone cement around the knee prosthesis. Moreover, the long-term effects and stability of the knee prosthesis are still debatable. The aim of this study was to examine whether the use of a tourniquet increases the thickness of the cement mantle and affects the postoperative blood loss and pain during primary total knee arthroplasty (TKA) using meta-analysis.

Methods

We searched the Cochrane Central Library, MEDLINE, Embase, PubMed, CNKI, and Wang Fang databases for randomized controlled trials (RCTs) on primary TKA, from inception to November 2019. All RCTs in primary TKA with and without a tourniquet were included. The meta-analysis was conducted using RevMan 5.2 software.

Results

A total of eight RCTs (677 knees) were analyzed. We found no significant difference in the age and sex of the patients. The results showed that the application of tourniquet affects the thickness of the bone cement around the tibial prosthesis (WMD = 0.16, 95%CI = 0.11 to 0.21, p < 0.00001). However, in our study, there was no significant difference in postoperative blood loss between the two groups was observed (WMD = 12.07, 95%CI = − 78.63 to 102.77, p = 0.79). The use of an intraoperative tourniquet can increase the intensity of postoperative pain (WMD = 1.34, 95%, CI = 0.32 to 2.36, p = 0.01).

Conclusions

Tourniquet application increases the thickness of the bone cement around the prosthesis and may thus increase the stability and durability of the prosthesis after TKA. The application of an intraoperative tourniquet can increase the intensity of postoperative pain.
Epidermal growth factor or platelet-rich plasma combined with induced membrane technique in the treatment of segmental femur defects: an experimental study
Authors: Bilal Ökkeş , Topak Duran , Kınaş Mustafa , Kurutaş Ergül Belge , Kızıldağ Betül , Bahar Abdulkadir Yasir
Published: December 2020

Objective

Extensive bone defects remain a therapeutic challenge necessitating alternative surgical approaches with better outcomes. Can increase the effectiveness of PRP or EGF treatment in surgical treatment of large bone defects with Masquelet technique?

Aim of this study examined potential therapeutic benefits of the Masquelet technique with induced membranes in combination with platelet-rich plasma (PRP) or epidermal growth factor (EGF) in a rat model of segmental femur defect.

Methods

Three groups each consisting of 20 Sprague-Dawley rats were defined as follows: EGF group, PRP group, and control group. A femoral bone defect was created and filled with antibiotic embedded polymethyl methacrylate. Half of the animals in each group were sacrificed at week 6 and the pseudo-membranes formed were analyzed. In the remaining half, the cement was removed and the space was filled with autograft. After another 6 weeks, the structures formed were examined radiologically, histologically, and biochemically.

Results

At week 6, both PRP and EGF groups had significantly higher membrane CD31, TGF-beta, and VEGF levels than controls. At week 12, when compared to controls, PRP and EGF groups had significantly higher membrane CD31 levels and the PRP group had significantly higher membrane TGF levels. Regarding bone tissue levels, PRP and EGF groups had significantly higher VEGF levels and the EGF group had significantly higher BMP levels. In addition, PRP and EGF groups had higher radiological scores than controls. However, the two experimental groups did not differ with respect to any parameter tested in this study.

Conclusion

Both PRP and EGF seem to be associated with histological, biochemical, and radiological improvements in experimental rat model of Masquelet technique, warranting in further clinical studies.

Level of evidence

Level 5
Vitamin D for prevention of sternotomy healing complications: REINFORCE-D trial
Authors: Čečrle Michal , Černý Dalibor , Sedláčková Eva , Míková Barbora , Dudková Vlasta , Drncová Eva , Pokusová Michala , Skalský Ivo , Tamášová Jana , Halačová Milada
Published: December 2020

Background

Most cardiac surgery patients undergo median sternotomy during open heart surgery. Sternotomy healing is an arduous, very complex, and multifactorial process dependent on many independent factors affecting the sternum and the surrounding soft tissues. Complication rates for median sternotomy range from 0.5 to 5%; however, mortality rates from complications are very variable at 7–80%. Low calcidiol concentration below 80 nmol/L results in calcium absorptive impairment and carries a risk of bone loss, which is considered as a risk factor in the sternotomy healing process. The primary objective of this clinical trial is to compare the incidence of all postoperative sternotomy healing complications in two parallel patient groups administered cholecalciferol or placebo. The secondary objectives are focused on general patient recovery process: sternal bone healing grade at the end of the trial, length of hospitalization, number of days spent in the ICU, number of days spent on mechanical lung ventilation, and number of hospital readmissions for sternotomy complications.

Methods

This clinical trial is conducted as monocentric, randomized, double-blind, placebo-controlled, with planned enrollment of 600 patients over 4 years, approximately 300 in the placebo arm and 300 in the treatment arm. Males and females from 18 to 95 years of age who fulfill the indication criteria for undergoing cardiac surgery with median sternotomy can be included in this clinical trial, if they meet the eligibility criteria.

Discussion

REINFORCE-D is the first monocentric trial dividing patients into groups based on serum calcidiol levels, and with dosing based on serum calcidiol levels. This trial may help to open up a wider range of postoperative healing issues.

Trial registration

EU Clinical Trials Register, EUDRA CT No: 2016-002606-39. Registered on September 8, 2016.
Locally recurrent extraskeletal myxoid chondrosarcoma of the shoulder: a case of complete neoadjuvant radiotherapy response
Authors: Improta Luca , Valeri Sergio , Alloni Rossana , Pagnoni Chiara , Mallozzi Santa Maria Francesco , Brunetti Beniamino , Greco Carlo , Aprile Irene , Maselli Mirella , Vincenzi Bruno , Gronchi Alessandro
Published: December 2020

Background

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue tumor that typically affects the lower limbs of men between the ages of 50 and 60. EMC of the shoulder is rare with a high risk of local recurrence and distant metastasis. A planned surgical excision in sarcoma referral centers (SRCs) is mandatory to obtain the best outcome. The role of chemotherapy (CHT) and Radiotherapy (RT) on soft tissue chondrosarcoma is still controversial.

Case presentation

A 47-year-old man presented to our referral center with a history of EMC in the right shoulder excised with microscopic positive surgical margins in a non-referral center. Staging imaging exams did not reveal distant metastasis or residual disease, but during follow-up a local recurrence was detected. After a multidisciplinary discussion, preoperative radiotherapy was administered with a total dose of 50 Gy, and then the patient underwent wide surgical excision. Histological examination was negative for viable tumor cells. No relapse occurred in a 24-months post-operative follow up.

Conclusions

The case here described suggests the importance of patient’s management in SRCs. A planned combined treatments with both surgery and RT seems to be the best choice to improve local control. RT seems to be promising within this specific histotype. Further studies are needed to confirm if the observed efficacy of combined treatments reflects in a consistent survival benefit for EMC patients.
Network coding for reliable video distribution in multi-hop device-to-device communications
Authors: Wang Lei , Liu Yu , Xu Jia , Yin Jun , Xu Lijie , Yang Yuwang
Published: December 2020

It is becoming more and more popular to share videos among multiple users. However, sharing video in traditional cellular networks will incur high expenses. Device-to-device (D2D) communication is one of the crucial technologies in the fifth-generation network, and it enables the devices to transmit data directly without the relay of base stations. This paper proposes a network-coding-based video distribution scheme for the D2D communication environment. The proposed scheme applies the network coding technology in the H.264 video transmission, which can protect crucial information of the video. This scheme enables the receivers to decode the original video with a high probability, especially in the networks with interferences. Both the simulation results and the actual experimental results show that using network coding technology in video transmission can improve the quality of the received video. Compared with the traditional scheme, the successful decoding rate of the proposed scheme is increased by$$46\%$$46%in our experimental settings.
In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells
Authors: Gonsalves Wilson I. , Jang Jin Sung , Jessen Erik , Hitosugi Taro , Evans Laura A. , Jevremovic Dragan , Pettersson Xuan-Mai , Bush Alexander Graham , Gransee Jaimee , Anderson Emilie I. , Kumar Shaji K. , Nair K. Sreekumaran
Published: December 2020

Background

Overexpression of c-Myc is required for the progression of pre-malignant plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant plasma cells in multiple myeloma (MM). c-Myc also increases glutamine anaplerosis into the tricarboxylic acid (TCA) cycle within cancer cells. Whether increased glutamine anaplerosis is associated with the progression of pre-malignant to malignant plasma cells is unknown.

Methods

Human volunteers (N = 7) and patients with MGUS (N = 11) and MM (N = 12) were prospectively recruited to undergo an intravenous infusion of 13C-labeled glutamine followed by a bone marrow aspiration to obtain bone marrow cells and plasma.

Results

Despite notable heterogeneity, stable isotope-resolved metabolomics (SIRM) revealed that the mean 13C-labeled glutamine anaplerosis into the TCA cycle was higher in malignant compared to pre-malignant bone marrow plasma cells relative to the remainder of their paired bone marrow mononuclear cells. RNA sequencing demonstrated a higher relative mRNA expression of c-Myc and glutamine transporters such as ASCT2 and SN2 in malignant compared to pre-malignant bone marrow plasma cells. Finally, higher quantitative levels of TCA cycle intermediates in the bone marrow plasma differentiated MM from MGUS patients.

Conclusion

Measurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.

Trial registration

NCT03384108 and NCT03119883
The simultaneous use of Emotional suppression and Situation selection to regulate emotions incrementally favors physiological responses
Authors: Thuillard Simon , Dan-Glauser Elise S.
Published: December 2020

Background

Emotion regulation alters the trajectories of emotional responses and, when effective, transforms the emotional responses to help individuals adapt to their environment. Previous research has mainly focused on the efficiency of regulation strategies performed individually at a given time. Yet, in daily life, it is likely that several strategies are often combined. Thus, we question in this study the combinatorial efficiency of two emotion regulation strategies, Situation selection and Emotional suppression.

Methods

In a within-subject design, sixty-five participants were asked to implement either no strategy, Situation selection only, Emotional suppression only, or both strategies together (four conditions) while looking at various emotionally charged images. Experience, expressivity, and physiological arousal were recorded throughout the viewing. Repeated-measures ANOVAs and corrected post-hoc tests were used for analyzing the data.

Results

The results of the combined strategies showed that Emotional suppression canceled the beneficial impact of Situation selection on negative experience, while significantly increasing the impact on cardiac activity. The use of both strategies together had a greater effect on respiratory function with an enhanced decrease in respiratory rate and amplitude.

Conclusions

The combinatorial effect of emotion regulation strategies is different according to the emotional response that the individual needs to regulate. The simultaneous use of Situation selection and Emotional suppression could be particularly beneficial to relieve physiological symptoms.
Case report series: Revisiting third and fourth pharyngeal arch anomalies, − are they thymopharyngeal duct remnants?
Authors: Kotwica A. O. , Rudd J. , Howard D. J.
Published: December 2020

Background

Pharyngeal arch anomalies are the second most common form of head and neck congenital defect. The second arch anomalies are the most common, and compromise 95% of cases. Little is known about the 3rd and 4th arch anomalies as they are extremely rare. They most commonly present in childhood with sudden severe left lateral neck infection and abscess formation with considerable tendency to recur, contributing to significant mortality and morbidity in those patients.

Case presentation

Here we present four cases finally diagnosed as third or fourth pharyngeal arch anomalies, with more than 20 years of follow-up following their definitive surgery. The possibility that they are thymopharyngeal duct remnants is discussed.

Conclusion

Meticulous open radical surgical excision of all involved paralaryngeal, parapharyngeal and thyroid tissue, with preservation of the superior and recurrent laryngeal nerves, is required for cure of recurrent cases.

Graphical abstract
Label-free vibrational imaging of different Aβ plaque types in Alzheimer’s disease reveals sequential events in plaque development
Authors: Röhr Dominik , Boon Baayla D. C. , Schuler Martin , Kremer Kristin , Hoozemans Jeroen J. M. , Bouwman Femke H. , El-Mashtoly Samir F. , Nabers Andreas , Großerueschkamp Frederik , Rozemuller Annemieke J. M. , Gerwert Klaus
Published: December 2020

The neuropathology of Alzheimer’s disease (AD) is characterized by hyperphosphorylated tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques. Aβ plaques are hypothesized to follow a development sequence starting with diffuse plaques, which evolve into more compact plaques and finally mature into the classic cored plaque type. A better molecular understanding of Aβ pathology is crucial, as the role of Aβ plaques in AD pathogenesis is under debate. Here, we studied the deposition and fibrillation of Aβ in different plaque types with label-free infrared and Raman imaging. Fourier-transform infrared (FTIR) and Raman imaging was performed on native snap-frozen brain tissue sections from AD cases and non-demented control cases. Subsequently, the scanned tissue was stained against Aβ and annotated for the different plaque types by an AD neuropathology expert. In total, 160 plaques (68 diffuse, 32 compact, and 60 classic cored plaques) were imaged with FTIR and the results of selected plaques were verified with Raman imaging. In diffuse plaques, we detect evidence of short antiparallel β-sheets, suggesting the presence of Aβ oligomers. Aβ fibrillation significantly increases alongside the proposed plaque development sequence. In classic cored plaques, we spatially resolve cores containing predominantly large parallel β-sheets, indicating Aβ fibrils. Combining label-free vibrational imaging and immunohistochemistry on brain tissue samples of AD and non-demented cases provides novel insight into the spatial distribution of the Aβ conformations in different plaque types. This way, we reconstruct the development process of Aβ plaques in human brain tissue, provide insight into Aβ fibrillation in the brain, and support the plaque development hypothesis.
The effect of recombinant human soluble thrombomodulin on renal function and mortality in septic disseminated intravascular coagulation patients with acute kidney injury: a retrospective study
Authors: Akatsuka Masayuki , Masuda Yoshiki , Tatsumi Hiroomi , Sonoda Tomoko
Published: December 2020

Background

Clinical evidence showing the effectiveness of recombinant human soluble thrombomodulin (rhTM) for treating sepsis-induced disseminated intravascular coagulation (DIC) and organ dysfunction (particularly renal injury) is limited because of differences in the inclusion criteria and disease severity among patients. This study aimed to assess the association between rhTM and outcomes in septic DIC patients with acute kidney injury (AKI).

Methods

This retrospective observational study analyzed the data of patients who were admitted to the intensive care unit (ICU) of a single center between January 2012 and December 2018, and diagnosed with sepsis-induced DIC and AKI. Data were extracted as follows: patients’ characteristics; DIC score, as calculated by the Japanese Association for Acute Medicine and the International Society of Thrombosis and Hemostasis criteria; serum creatinine levels; and ICU and 28-day mortality rates. The primary outcome was the dependence on renal replacement therapy (RRT) at ICU discharge. The propensity score (PS) was calculated using the following variables: age, sex, septic shock at admission, DIC score, and KDIGO classification. Subsequently, logistic regression analysis was performed using the PS to evaluate the outcome.

Results

In total, 97 patients were included in this study. Of these, 52 (53.6%) patients had received rhTM. The dependence on RRT at ICU discharge was significantly lower in the rhTM than in the non-rhTM group (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.19–0.97; P = 0.043). The serum creatinine levels at ICU discharge (OR, 0.31; 95% CI, 0.13–0.72; P = 0.007) and hospital discharge (OR, 0.25; 95% CI, 0.11–0.60; P = 0.002, respectively), and the 28-day mortality rate (OR, 0.40; 95% CI, 0.17–0.93; P = 0.033) were significantly lower in the rhTM than in the non-rhTM group. Moreover, the Kaplan–Meier survival curve revealed significantly lower mortality rates in the rhTM than in the non-rhTM group (P = 0.009). No significant differences in the DIC score and AKI severity were observed between the groups.

Conclusions

Among sepsis-induced DIC patients with AKI, rhTM administration was associated with lower dependence on RRT at ICU discharge, improvement in renal function, and lower 28-day mortality rate.
Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation
Authors:   Lawson COVID19 Study Team, Gill Sean E. , dos Santos Claudia C. , O’Gorman David B. , Carter David E. , Patterson Eric K. , Slessarev Marat , Martin Claudio , Daley Mark , Miller Michael R. , Cepinskas Gediminas , Fraser Douglas D.
Published: December 2020

Background

COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.

Results

We enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19− patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 + patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling.

Conclusions

Our findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19− patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.
Cytotoxic metabolites from Thysanolaena maxima Roxb. available in Bangladesh
Authors: Hoque Nazia , Sohrab Md. Hossain , Afroz Farhana , Rony Satyajit Roy , Sharmin Suriya , Moni Fatema , Hasan Choudhury Mahmood , Rana Md. Sohel
Published: December 2020

Background

Thysanolaena maxima (Roxb.) Kuntze, a perennial grass plant, is usually distributed in hilly regions of the Indian Subcontinent. Different parts of T. maxima have been used as herbal medicine by traditional healers of this region. In this present study, T. maxima plant extract has been screened for examination of its secondary metabolite content with their probable cytotoxic activity.

Methods

Secondary metabolites of the crude T. maxima plant extract were isolated by different chromatographic methods. The structures were elucidated by spectroscopic data (1H NMR, 13C NMR) as well as comparison with available literature sources. Antiradical activity by DPPH radical scavenging assay and antimicrobial activity by disc diffusion method of the fractions and cytotoxic activity by trypan blue exclusion method of the isolated compounds were also evaluated.

Results

Three phenolic compounds 4-hydroxybenzaldehyde (1), 4-hydroxycinnamic acid (2), 4-hydroxybenzoic acid (3) and two steroids stigmast-4-en-3-one (4) and β-stigmasterol (5) were isolated from the aerial part of T. maxima. Among the compounds 4-hydroxycinnamic acid, 4-hydroxybenzoic acid and stigmast-4-en-3-one exhibited notable cytotoxic activity against African Green Monkey Kidney Cell line (Vero cell).

Conclusion

Bioassay investigation of the isolated compounds and fractions suggested that T. maxima could be a potential source of bioactive secondary metabolites.

Graphical abstract
Implementation of enhanced recovery after surgery in gynecological operations: a randomized controlled trial
Authors: Abdelrazik Amr Nady , Sanad Ahmad Sameer
Published: December 2020

Background

To investigate the effects of enhanced recovery after surgery (ERAS) in patients undergoing gynecologic surgery on length of hospital stay, pain management, and complication rate.

Results

The length of hospital stay was reduced in ERAS groups when compared with the control groups (3.46 days vs 2.28 days; P < 0.0001; CI − 1.5767 to − 0.7833 for laparotomy groups and 2.18 vs 1.76 days; P = 0.0115; CI − 0.7439 to − 0.0961 for laparoscopy groups respectively). Intraoperative fluid use was reduced in both ERAS groups compared to the two control groups (934 ± 245 ml and 832 ± 197 ml vs 1747 ± 257 ml and 1459 ± 304 respectively; P < 0.0001) and postoperative fluid use was also less in the ERAS groups compared to the control groups (1606 ± 607 ml and 1210 ± 324 ml vs 2682 ± 396 ml and 1469 ± 315 ml respectively; P < 0.0001). Pain score using visual analog scale (VAS) on postoperative day 0 was 4.8 ± 1.4 and 4.1 ± 1.2 (P = 0.0066) for both laparotomy control and ERAS groups respectively, while in the laparoscopy groups, VAS was 3.8 ± 1.1 and 3.2 ± 0.9 (P = 0.0024) in control and ERAS groups respectively.

Conclusion

Implementation of ERAS protocols in gynecologic surgery was associated with significant reduction in length of hospital stay, associated with decrease intravenous fluids used and comparable pain control without increase in complication rates.
Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co-polymer
Authors: Ozoude Chukwuebuka H. , Azubuike Chukwuemeka P. , Ologunagba Modupe O. , Tonuewa Sejoro S. , Igwilo Cecilia I.
Published: December 2020

Background

Khaya gum is a bark exudate from Khaya senegalensis (Maliaecae) that has drug carrier potential. This study aimed to formulate and comparatively evaluate metformin-loaded microspheres using blends of khaya gum and sodium alginate. Khaya gum was extracted and subjected to preformulation studies using established protocols while three formulations (FA; FB and FC) of metformin (1% w/v)-loaded microspheres were prepared by the ionic gelation method using 5% zinc chloride solution as the cross-linker. The formulations contained 2% w/v blends of khaya gum and sodium alginate in the ratios of 2:3, 9:11, and 1:1, respectively. The microspheres were evaluated by scanning electron microscopy, Fourier transform-infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, swelling index, and in vitro release studies.

Results

Yield of 28.48%, pH of 4.00 ± 0.05, moisture content (14.59% ± 0.50), and fair flow properties (Carr’s index 23.68 ± 1.91 and Hausner’s ratio 1.31 ± 0.03) of the khaya gum were obtained. FTIR analyses showed no significant interaction between pure metformin hydrochloride with excipients. Discrete spherical microspheres with sizes ranging from 1200 to 1420 μm were obtained. Drug entrapment efficiency of the microspheres ranged from 65.6 to 81.5%. The release of the drug from microspheres was sustained for the 9 h of the study as the cumulative release was 62% (FA), 73% (FB), and 80% (FC). The release kinetics followed Korsmeyer-Peppas model with super case-II transport mechanism.

Conclusion

Blends of Khaya senegalensis gum and sodium alginate are promising polymer combination for the preparation of controlled-release formulations. The blend of the khaya gum and sodium alginate produced microspheres with controlled release properties. However, the formulation containing 2:3 ratio of khaya gum and sodium alginate respectively produced microspheres with comparable controlled release profiles to the commercial brand metformin tablet.
Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity
Authors: Padmanabhan Krishnanand , Grobe Hanna , Cohen Jonathan , Soffer Arad , Mahly Adnan , Adir Orit , Zaidel-Bar Ronen , Luxenburg Chen
Published: December 2020

Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)-actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment.