bluuebunny/crossref_metadata_2025 huggingface dataset:
MR1-dependence of unmetabolized folic acid side-effects
Authors: Tang Jeffry S. , Cait Alissa , White Reuben M. , Arabshahi Homayon J. , O’Sullivan David , Gasser Olivier
Published: August 2022

The fortification of flour with folic acid for the prevention of neural tube defects (NTD) is currently mandated in over eighty countries worldwide, hence compelling its consumption by the greater part of the world’s population. Notwithstanding its beneficial impact on rates of NTD, pervasive folic acid supplementation has invariably led to additive daily intakes reaching well beyond their original target, resulting in the circulation of unmetabolized folic acid. Associated idiopathic side-effects ranging from allergies to cancer have been suggested, albeit inconclusively. Herein, we hypothesize that their inconsistent detection and elusive etiology are linked to the in vivo generation of the immunosuppressive folic acid metabolite 6-formylpterin, which interferes with the still emerging and varied functions of Major Histocompatibility Complex-related molecule 1 (MR1)-restricted T cells. Accordingly, we predict that fortification-related adverse health outcomes can be eliminated by substituting folic acid with the bioequivalent folate vitamer 5-methyltetrahydrofolate, which does not break down into 6-formylpterin.
Monoclonal antibody therapy of herpes simplex virus: An opportunity to decrease congenital and perinatal infections
Authors: Backes Iara M. , Leib David A. , Ackerman Margaret E.
Published: August 2022

The fetal/neonatal period represents both a unique window of opportunity for interventions as well as vulnerability to a number of viral infections. WhileHerpesvirusessuch as herpes simplex virus (HSV) are highly prevalent and typically of little consequence among healthy adults, they are among the most consequential infections of early life. Despite treatment with antiviral drugs, neonatal HSV (nHSV) infections can still result in significant mortality and lifelong neurological morbidity. Fortunately, newborns in our pathogen-rich world inherit some of the protection provided by the maternal immune system in the form of transferred antibodies. Maternal seropositivity, resulting in placental transfer of antibodies capable of neutralizing virus and eliciting the diverse effector functions of the innate immune system are associated with dramatically decreased risk of nHSV. Given this clear epidemiological evidence of reduced risk of infection and its sequelae, we present what is known about the ability of monoclonal antibody therapies to treat or prevent HSV infection and explore how effective antibody-based interventions in conjunction with antiviral therapy might reduce early life mortality and long-term morbidity.
Neutrophil to lymphocyte ratio predicting poor outcome after aneurysmal subarachnoid hemorrhage: A retrospective study and updated meta-analysis
Authors: Guo Yinghan , Liu Jiang , Zeng Hanhai , Cai Lingxin , Wang Tingting , Wu Xinyan , Yu Kaibo , Zheng Yonghe , Chen Huaijun , Peng Yucong , Yu Xiaobo , Yan Feng , Cao Shenglong , Chen Gao
Published: August 2022

Background

The relationship between neutrophil to lymphocyte ratio (NLR) and poor outcome of aneurysmal subarachnoid hemorrhage (aSAH) is controversial. We aim to evaluate the relationship between NLR on admission and the poor outcome after aSAH.

Method

Part I: Retrospective analysis of aSAH patients in our center. Baseline characteristics of patients were collected and compared. Multivariate analysis was used to evaluate parameters independently related to poor outcome. Receiver operating characteristic (ROC) curve analysis was used to determine the best cut-off value of NLR. Part II: Systematic review and meta-analysis of relevant literature. Related literature was selected through the database. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to evaluate the correlation between NLR and outcome measures.

Results

Part I: A total of 240 patients with aSAH were enrolled, and 52 patients had a poor outcome. Patients with poor outcome at 3 months had a higher admission NLR, Hunt & Hess score, Barrow Neurological Institute (BNI) scale score, Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and proportion of hypertension history. After adjustment, NLR at admission remained an independent predictor of poor outcome in aSAH patients (OR 0.76, 95% CI 0.69-0.83; P < 0.001). The best cut-off value of NLR in ROC analysis is 12.03 (area under the curve 0.805, 95% CI 0.735 - 0.875; P < 0.001). Part II: A total of 16 literature were included. Pooled results showed that elevated NLR was significantly associated with poor outcome (OR 1.31, 95% CI 1.14-1.49; P < 0.0001) and delayed cerebral ischemia (DCI) occurrence (OR 1.32, 95% CI 1.11-1.56; P = 0.002). The results are more reliable in large sample sizes, low NLR cut-off value, multicenter, or prospective studies.

Conclusion

Elevated NLR is an independent predictor of poor outcome and DCI occurrence in aSAH.
Nano-Chemotherapy synergize with immune checkpoint inhibitor- A better option?
Authors: Qian Xinye , Hu Wang , Yan Jun
Published: August 2022

Immune checkpoint inhibitor (ICI) is one of the most important tumor treatment methods. Although the therapeutic efficiency of immune checkpoint inhibitor mono-therapy is limited, the combination of chemotherapy plus immune checkpoint inhibitors has shown great advantages in cancer treatment. This is mainly due to the fact that tumor reactive T cells could fully provide their anti-tumor function as chemotherapy could not only cause immunogenic cell death to increase antigen presentation, but also improve the immunosuppressive tumor micro-environment to synergize with immune checkpoint inhibitors. However, traditional chemotherapy still has shortcomings such as insufficient drug concentration in tumor region, short drug duration, drug resistance, major adverse events, etc, which might lead to the failure of the therapy. Nano chemotherapeutic drugs, which refer to chemotherapeutic drugs loaded in nano-based drug delivery system, could overcome the above shortcomings of traditional chemotherapeutic drugs to further improve the therapeutic effect of immune checkpoint inhibitors on tumors. Therefore, the scheme of nano chemotherapeutic drugs combined with immune checkpoint inhibitors might lead to improved outcome of cancer patients compared with the scheme of traditional chemotherapy combined with immune checkpoint inhibitors.
How to successfully administer palliative treatment with a stent for malignant gastric outlet obstruction?
Authors: Maetani Iruru
Published: August 2022

Although endoscopic stenting (ES) has been widely used as a less-invasive palliation method for malignant gastric outlet obstruction (GOO), recent reports have highlighted issues related to the procedure. For successful treatment, various aspects must be assessed before considering the practices. First, it is necessary to eliminate cases with contraindications such as coexistence of distal small-bowel obstruction or perforation. Other factors potentially related to clinical failure (i.e., peritoneal carcinomatosis) may require consideration but remain controversial. ES has better short-term outcomes than surgical gastrojejunostomy (GJ). GJ has recently been considered preferable in cases with longer life expectancy because of superior sustainability. Various types of stents are now commercially available, but their ideal structure and mechanical properties have not yet been clarified. Covered metal stent may reduce stent obstruction but is prone to increase stent migration, and its significance remains uncertain. Subsequent chemotherapy after stenting should be considered, as it is expected to prolong patient survival without increasing the risk of adverse events. Furthermore, it may be helpful in preventing tumor ingrowth. In cases with GOO combined with biliary obstruction, biliary intervention is often difficult. Recently, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been widely used as an alternative procedure for endoscopic transpapillary biliary drainage (ETBD). Despite the lack of consensus as to whether ETBD or EUS-BD is preferred, EUS-BD is useful as a salvage technique for cases where ETBD is difficult. To perform stent placement successfully, it is important to pay attention to the above points; however, many remaining issues need to be clarified in the future.
Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study)
Authors: Dargent Auguste , Bourredjem Abderrahmane , Argaud Laurent , Levy Bruno , Fournel Isabelle , Cransac Amélie , Badie Julio , Quintin Luc , Quenot Jean-Pierre
Published: August 2022

Introduction

Refractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial.

Methods

This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent.

Discussion

The present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients.

Trial registration

Registered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.
Dynamicity and persistence of severe acute respiratory syndrome coronavirus-2 antibody response after double dose and the third dose with BBV-152 and AZD1222 vaccines: A prospective, longitudinal cohort study
Authors: Parai Debaprasad , Choudhary Hari Ram , Dash Girish Chandra , Behera Susmita , Mishra Narayan , Pattnaik Dipti , Raghav Sunil Kumar , Mishra Sanjeeb Kumar , Sahoo Subrat Kumar , Swain Aparajita , Mohapatra Ira , Pattnaik Matrujyoti , Moharana Aparnamayee , Jena Sandhya Rani , Praharaj Ira , Subhadra Subhra , Kanungo Srikanta , Bhattacharya Debdutta , Pati Sanghamitra
Published: August 2022

Introduction

Vaccines are available worldwide to combat coronavirus disease-19 (COVID-19). However, the long-term kinetics of the vaccine-induced antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been sufficiently evaluated. This study was performed to investigate the persistence and dynamicity of BBV-152 (Covaxin)- and AZD1222 (Covishield)-induced immunoglobulin-G (IgG) antibodies over the year and neutralizing antibodies’ status after 1-month of booster dose.

Materials and methods

This 52-week longitudinal cohort study documented antibody persistence and neutralizing antibodies status among 304 healthcare workers (HCWs) from six hospitals and research facilities in Odisha, enrolled during January 2021 and continued till March 2022. IgG antibodies against spike receptor-binding domain (RBD) of SARS-CoV-2 were quantified in an automated chemiluminescence immune assay-based (CLIA) platform and a surrogate virus neutralization test (sVNT) was performed by enzyme-linked immunosorbent assay (ELISA).

Results

Among these 304 HCWs vaccinated with double doses, 154 HCWs (50.66%) were Covaxin recipients and the remaining 150 (49.34%) were Covishield recipients. During the follow-ups for seven times, a total of 114 participants were identified as vaccine breakthrough cases. In 190 non-infected HCWs, the median antibody titer was significantly waned from DD2 to DD10, both for Covaxin (231.8 vs. 42.7 AU/ml) and Covishield (1,884.6 vs. 369.2 AU/ml). No statistically significant differences in antibody titers were observed based on age, gender, comorbidities, and blood groups. The median inhibition activity of sVNT increased from 23.8 to 91.3% for Covaxin booster recipients and from 41.2 to 96.0% for Covishield booster recipients. Among 146 booster dose recipients, 48 were breakthrough cases after booster and all were contracted by the omicron variant.

Conclusion

This year-long follow-up study found a 7- and 5-fold antibody waning in Covaxin and Covishield recipients, respectively, without any breakthrough infection history. However, individuals with booster breakthrough had mild symptoms and did not require hospital admission. The data also indicate the possible escape of omicron variants despite the presence of vaccine-induced neutralizing antibodies.
Development and evaluation of culture media based on extracts of the cyanobacterium Arthrospira platensis
Authors: Kheirabadi Elaheh , Macia Javier
Published: August 2022

Continuous advances in the fields of industrial biotechnology and pharmacy require the development of new formulations of culture media based on new nutrient sources. These new sources must be sustainable, high yielding, and non-animal-based, with minimal environmental impact. Thus, culture media prepared from cyanobacterial extracts can be an interesting alternative to the current formulations. In this study, we prepared various minimal formulations of culture media using the extracts of Arthrospira platensis, and analyzed the efficiency of these formulations, based on their effect on the production of biomass and molecules of industrial interest, using different types of bacteria. All media formulations prepared in this study showed better performance than conventional media, including those based on animal ingredients. Thus, based on their versatility and high-yielding capacity, we conclude that culture media prepared from cyanobacterial extracts are a good alternative to conventional media for meeting the current demands of the cosmetic and pharmaceutical industries.
Crosstalk between regulatory non-coding RNAs and oxidative stress in Parkinson’s disease
Authors: Zhang Hantao , Liu Xiaoyan , Liu Yi , Liu Junlin , Gong Xun , Li Gang , Tang Min
Published: August 2022

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease, which imposes an ever-increasing burden on society. Many studies have indicated that oxidative stress may play an important role in Parkinson’s disease through multiple processes related to dysfunction or loss of neurons. Besides, several subtypes of non-coding RNAs are found to be involved in this neurodegenerative disorder. However, the interplay between oxidative stress and regulatory non-coding RNAs in Parkinson’s disease remains to be clarified. In this article, we comprehensively survey and overview the role of regulatory ncRNAs in combination with oxidative stress in Parkinson’s disease. The interaction between them is also summarized. We aim to provide readers with a relatively novel insight into the pathogenesis of Parkinson’s disease, which would contribute to the development of pre-clinical diagnosis and treatment.
Effect of rearfoot valgus on biomechanics during barbell squatting: A study based on OpenSim musculoskeletal modeling
Authors: Lu Zhenghui , Li Xin , Rong Ming , Baker Julien S. , Gu Yaodong
Published: August 2022

Background

Barbell squats are commonly used in daily training and rehabilitation. Injuries are not common when the posture is standard, but the wrong posture can lead to injuries. Rearfoot valgus is a common foot abnormality that may increase the risk of injury during sports. The purpose of this study was to compare the biomechanics of lower limbs in normal foot and valgus patients during barbell squat.

Methods

In this study, 10 participants with normal foot shape and 10 participants with rearfoot valgus were enrolled. The joint angle, joint moment, and range of motion of hip, knee, and ankle joints were collected under 0, 30, and 70% one-repetition maximum (RM) load, where discrete data are statistically analyzed using the independent sample t-test, and continuous data are statistically analyzed using one-dimensional parameter statistical mapping.

Results

In barbell squats, the range of motion and the joint moment of the hip, knee, and ankle in the rearfoot valgus participants were significantly larger than those in normal foot participants (p < 0.05). The participants with rearfoot valgus had a more significant knee valgus angle when squatting to the deepest (p < 0.05). In addition, with the increase in load, the participants with rearfoot valgus showed greater standardized medial knee contact force (p < 0.05). In the process of barbell squats, the participants with rearfoot valgus showed no significant difference in the foot valgus angle when compared with the normal foot shape (p > 0.05).

Conclusions

The valgus population showed a greater range of joint motion when performing barbell squats and showed genu valgus and greater medial knee contact force, which may increase the risk of musculoskeletal and soft tissue damage such as meniscus wear. In addition, there was no significant difference in the rearfoot valgus angle between people with rearfoot valgus and people with normal foot shape during squatting, so barbell squatting may correct valgus to a certain extent.
Case report: A novel loss-of-function pathogenic variant in the KCNA1 cytoplasmic N-terminus causing carbamazepine-responsive type 1 episodic ataxia
Authors: Manville Rían W. , Sidlow Richard , Abbott Geoffrey W.
Published: August 2022

Episodic ataxia is an umbrella term for a group of nervous system disorders that adversely and episodically affect movement. Episodes are recurrent, characterized by loss of balance and coordination and can be accompanied by other symptoms ranging from nausea to hemiplegia. Episodic Ataxia Type 1 (EA1) is an inherited, autosomal dominant disease caused by sequence variants in KCNA1, which encodes the voltage-gated potassium channel, KCNA1 (Kv1.1). Here we report a novel loss-of-function KCNA1 pathogenic variant [c.464T>C/p.Leu155Phe] causing frequent, sudden onset of clumsiness or staggering gait in the young female proband. The gene variant was maternally inherited and the mother, whose symptoms also began in childhood, has a normal MRI and EEG, slurred speech and dystonic movements involving upper extremities and mouth. Both mother and daughter are responsive to carbamazepine. Cellular electrophysiology studies of KCNA1-L155P potassium channels revealed complete but non-dominant loss of function, with reduced current and altered gating in heterozygous channels. To our knowledge this is the first EA1-associated pathogenic variant located in the KCNA1 cytoplasmic N-terminus, expanding the reported clinically sensitive domains of the channel.
Intrinsic brain abnormalities in female major depressive disorder patients with childhood trauma: A resting-state functional magnetic resonance imaging study
Authors: Chen Juran , Luo Qianyi , Li Yuhong , Wu Zhiyao , Lin Xinyi , Yao Jiazheng , Yu Huiwen , Nie Huiqin , Du Yingying , Peng Hongjun , Wu Huawang
Published: August 2022

Objective

Childhood trauma is a strong predictor of major depressive disorder (MDD). Women are more likely to develop MDD than men. However, the neural basis of female MDD patients with childhood trauma remains unclear. We aimed to identify the specific brain regions that are associated with female MDD patients with childhood trauma.

Methods

We recruited 16 female MDD patients with childhood trauma, 16 female MDD patients without childhood trauma, and 20 age- and education level-matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging (MRI). Regional brain activity was evaluated as the amplitude of low-frequency fluctuation (ALFF). Furthermore, functional connectivity (FC) analyses were performed on areas with altered ALFF to explore alterations in FC patterns.

Results

There was increased ALFF in the left middle frontal gyrus (MFG) and the right postcentral gyrus (PoCG) in MDD with childhood trauma compared with MDD without childhood trauma. The areas with significant ALFF discrepancies were selected as seeds for the FC analyses. There was increased FC between the left MFG and the bilateral putamen gyrus. Moreover, ALFF values were correlated with childhood trauma severity.

Conclusion

Our findings revealed abnormal intrinsic brain activity and FC patterns in female MDD patients with childhood trauma, which provides new possibilities for exploring the pathophysiology of this disorder in women.
An energy-efficient in-memory computing architecture for survival data analysis based on resistive switching memories
Authors: Baroni Andrea , Glukhov Artem , Pérez Eduardo , Wenger Christian , Calore Enrico , Schifano Sebastiano Fabio , Olivo Piero , Ielmini Daniele , Zambelli Cristian
Published: August 2022

One of the objectives fostered in medical science is the so-called precision medicine, which requires the analysis of a large amount of survival data from patients to deeply understand treatment options. Tools like machine learning (ML) and deep neural networks are becoming a de-facto standard. Nowadays, computing facilities based on the Von Neumann architecture are devoted to these tasks, yet rapidly hitting a bottleneck in performance and energy efficiency. The in-memory computing (IMC) architecture emerged as a revolutionary approach to overcome that issue. In this work, we propose an IMC architecture based on resistive switching memory (RRAM) crossbar arrays to provide a convenient primitive for matrix-vector multiplication in a single computational step. This opens massive performance improvement in the acceleration of a neural network that is frequently used in survival analysis of biomedical records, namely the DeepSurv. We explored how the synaptic weights mapping strategy and the programming algorithms developed to counter RRAM non-idealities expose a performance/energy trade-off. Finally, we discussed how this application is tailored for the IMC architecture rather than being executed on commodity systems.
Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy
Authors: Liu Chengzhi , Dong Wenkang , Lv Zhengshuai , Kong Li , Ren Xiang
Published: August 2022

Diabetic retinopathy (DR) is a common complication of diabetes mellitus and has been considered a microvascular disease for a long time. However, recent evidence suggests that diabetic retinal neurodegeneration (DRN), which manifests as neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis, occurs prior to retinal microvascular alterations. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of thioredoxin (Trx), and it acts by inhibiting its reducing capacity, thereby promoting cellular oxidative stress. In addition, it participates in regulating multiple signaling pathways as a member of the α-arrestin family of proteins. Accumulating evidence suggests that TXNIP is upregulated in diabetes and plays a pivotal role in the pathophysiological process of DR. In this review, we summarized the role of TXNIP in DRN, aiming to provide evidence for DR treatment in the future.
Long-term oncological outcomes of oncoplastic breast-conserving surgery after a 10-year follow-up – a single center experience and systematic literature review
Authors: Hing Jun Xian , Kang Byeong Ju , Keum Hee Jung , Lee Jeeyeon , Jung Jin Hyang , Kim Wan Wook , Yang Jung Dug , Lee Joon Seok , Park Ho Yong
Published: August 2022

Aim

While many studies reported the oncological outcomes of oncoplastic breast-conserving surgery (OBCS), there were inherent differences in the study population, surgeons’ expertise, and classifications of techniques used. There were also limited studies with long term follow up oncological outcomes beyond 5 years. This current study aimed to compare long-term oncological outcomes of ipsilateral breast tumor recurrence (IBTR) disease-free survival (DFS) and overall survival (OS) following conventional and oncoplastic breast-conserving surgery using volume displacement and replacement techniques.

Methods

Between 2009 and 2013, 539 consecutive patients who underwent breast conservation surgery including 174 oncoplastic and 376 conventional procedures were analysed. A systematic review of studies with at least five years of median follow up were performed to compare long term oncological outcomes.

Results

At a median follow-up of 82.4 months, there were 23 (4.2%) locoregional recurrences, 17 (3.2%) metachronous contralateral breast cancer, 26 (4.8%) distant metastases, and 13 (2.4%) deaths. The hazard ratio of OBCS for IBTR, DFS and OS were 0.78 (95% confidence interval [CI] 0.21–2.94, p=0.78), 1.59 (95% CI, 0.88 to 2.87, p=0.12), and 2.1 (95% CI, 0.72 to 5.9, p=0.17) respectively. The 10-year IBTR-free, DFS and OS rate were 97.8%, 86.2%, and 95.7% respectively.

Conclusion

There remained a dearth in well-balanced comparative studies with sufficient long-term follow-up, and our study reported long-term oncological outcomes for OBCS which were favourable of either VD or replacement techniques.
Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database
Authors: Ye Yong , Zhang Bo , Liang Qiuyun , Wang Dandan , Bai Facheng , Li Yuanhong , Wei Lizhi , Li Lilan , Huang Huixue , Tang Yunxia
Published: August 2022

Background

Breast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the underlying mechanism remains unclear and needs to be fully elucidated.

Methods

The active constituents of CKI were identified through a literature review, and the anti-BC targets of CKI were determined using multiple databases and a ChIP data analysis. Subsequently, the target was analyzed on the DAVID database through GO and KEGG to identify the key pathway that CKI affects to exhibit anti-BC activity. In addition, MCF-7 and MDA-MB-231 cells were treated with CKI for 24 and 48 hours at five concentrations, and the effects of CKI on cell proliferation and apoptosis were measured using MTT and annexin V/propidium iodide staining assays, respectively. The genes and protein identified to be involved in this pathway were verified using real-time quantitative PCR (qPCR) and western blot(WB) in BC cells.

Results

Twelve CKI anti-BC targets were obtained by a comprehensive analysis of the targets collected in the databases and results from the ChIP analysis. Bioinformatics analysis was performed for 12 targets. KEGG analysis showed that the 12 targets were mainly related to the VEGF, ErbB, and TNF signaling pathways. We focused our study on the VEGF signaling pathway as the p-value for the VEGF signaling pathway was the lowest among the three pathways. In vitro experiments showed that CKI significantly inhibited the proliferation of BC cells and induced apoptosis. Furthermore, qPCR and WB experiments showed that the expression of VEGF signaling pathway genes PIK3CA and NOS3 were significantly increased meanwhile SRC was significantly decreased after CKI intervention.

Conclusion

CKI significantly inhibited the proliferation of BC cells and induced apoptosis. The main mechanism for the anti-BC effect of CKI may be that it regulates the VEGF signaling pathway by increasing the expression of PIK3CA, SRC, and NOS3. Macrozamin and lamprolobine may be the main active components of CKI against BC.
Association between microRNA 671 polymorphisms and the susceptibility to soft tissue sarcomas in a Chinese population
Authors: Zhang Peng , Li Xinling , Huang Lingling , Hu Fulan , Niu Xiaoying , Sun Yang , Yao Weitao
Published: August 2022

This study evaluated the association between the microRNA (miRNA) gene polymorphisms and the susceptibility to soft tissue sarcomas (STSs). In this case–control study, DNA was extracted from leukocytes in peripheral blood, which was collected from 169 STSs patients and 170 healthy controls. Three SNPs for miR-210, five SNPs for miR-206, two SNPs for miR-485, two SNPs for miR-34b, two SNPs for miR-671, and three SNPs for miR-381 were investigated and genotyped using a Sequenom Mass ARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform. Unconditional logistic regression analysis was used to analyze the association between miRNA gene polymorphisms and the susceptibility to STSs. The results showed that miR-671 rs1870238 GC + CC (OR = 1.963, 95% CI = 1.258–3.064, P = 0.003) and miR-671 rs2446065 CG + GG (OR =1.838, 95% CI = 1.178–2.868, P = 0.007) may be genetic risk factors for STSs after adjustment for age and smoking. Therefore, this study suggests that individuals carrying the GC + CC genotype for miR-671 rs1870238 or the CG + GG genotype for miR-671 rs2446065 are susceptible to STSs.
Radiomics based on pretreatment MRI for predicting distant metastasis of nasopharyngeal carcinoma: A preliminary study
Authors: Jiang Tingting , Tan Yalan , Nan Shuaimin , Wang Fang , Chen Wujie , Wei Yuguo , Liu Tongxin , Qin Weifeng , Lu Fangxiao , Jiang Feng , Jiang Haitao
Published: August 2022

Objective

To explore the feasibility of predicting distant metastasis (DM) of nasopharyngeal carcinoma (NPC) patients based on MRI radiomics model.

Methods

A total of 146 patients with NPC pathologically confirmed, who did not exhibit DM before treatment, were retrospectively reviewed and followed up for at least one year to analyze the DM risk of the disease. The MRI images of these patients including T2WI and CE-T1WI sequences were extracted. The cases were randomly divided into training group (n=116) and validation group (n=30). The images were filtered before radiomics feature extraction. The least absolute shrinkage and selection operator (LASSO) regression was used to develop the dimension of texture parameters and the logistic regression was used to construct the prediction model. The ROC curve and calibration curve were used to evaluate the predictive performance of the model, and the area under curve (AUC), accuracy, sensitivity, and specificity were calculated.

Results

72 patients had DM and 74 patients had no DM. The AUC, accuracy, sensitivity and specificity of the model were 0. 80 (95% CI: 0.72~0. 88), 75.0%, 76.8%, 73.3%. and0.70 (95% CI: 0.51~0.90), 66.7%, 72.7%, 63.2% in training group and validation group, respectively.

Conclusion

The radiomics model based on logistic regression algorithm has application potential for evaluating the DM risk of patients with NPC.
Apraclonidine—An eye opener
Authors: Fierz Fabienne C. , Disse Leah R. , Bockisch Christopher J. , Weber Konrad P.
Published: August 2022

Pharmacological testing with apraclonidine eye drops induces a typical reversal of anisocoria in patients with Horner’s syndrome. Moreover, apraclonidine was observed to have an elevating effect on the upper eyelid in Horner’s syndrome as well as in healthy subjects, which is thought to be mediated by alpha-1 adrenergic receptors present in the Muller’s muscle. We aim to quantitatively investigate the effect of apraclonidine on eyelid position in patients with Horner’s syndrome compared to physiological anisocoria based on infrared video recordings from pupillometry. We included 36 patients for analysis who underwent binocular pupillometry before and after apraclonidine 1% testing for the evaluation of anisocoria. Vertical eyelid measurements were taken from infrared videos and averaged from multiple pupillometry cycles. Receiver operating characteristic curves were calculated to determine the optimal cutoff value for change in eyelid aperture pre- and post-apraclonidine. A decrease of inter-eye difference in the aperture of >0.42 mm was discriminative of Horner’s syndrome compared to physiological anisocoria with a sensitivity of 80% and a specificity of 75%. Our data confirm an eyelid- elevating effect of the apraclonidine test, more pronounced in eyes with a sympathetic denervation deficit. Measuring eyelid aperture on pupillometry recordings may improve the diagnostic accuracy of apraclonidine testing in Horner’s syndrome.
Incidence and predictors of pericardial effusion following surgical closure of atrial septal defect in children: A single center experience
Authors: Campisano Martina , Celani Camilla , Franceschini Alessio , Pires Marafon Denise , Federici Silvia , Brancaccio Gianluca , Galletti Lorenzo , De Benedetti Fabrizio , Chinali Marcello , Insalaco Antonella
Published: August 2022

Objectives

To evaluate the incidence of pericardial effusion (PE) after surgical atrial septal defect (ASD) closure and to investigate the presence of predictive risk factors for its development.

Methods

We collected data from 203 patients followed at Bambino Gesù Children’s Hospital of Rome who underwent cardiac surgery for ASD repair between January 2015 and September 2019.

Results

A total of 200/203 patients with different types of ASD were included. Patients were divided into two groups: Group 1) 38 (19%) who developed PE and Group 2) 162 (81%) without PE. No differences were noted between the two groups with regard to gender or age at the surgery. Fever in the 48 h after surgery was significantly more frequent in group 1 than in group 2 (23.7 vs. 2.5%; p < 0.0001). ECG at discharge showed significant ST-segment elevation in children who developed PE, 24.3 vs. 2.0% in those who did not (p < 0.0001). Group 1 patients were divided into two subgroups on the basis of the severity of PE, namely, 31 (81.6%) with mild and 7 (18.4%) with moderate/severe PE. Patients with moderate/severe PE had a significantly higher BMI value (median 19.1 Kg/m2) (range 15.9–23.4, p = 0.004).

Conclusion

The presence of fever and ST-segment elevation after surgery predicts subsequent development of PE suggesting a closer follow-up for these categories of patients. A higher BMI appears to be associated with a higher risk of moderate/severe PE.
Mortality in children with cancer and SARS-CoV-2 in Latin America: A systematic review
Authors: Dorantes-Acosta Elisa , Ávila-Montiel Diana , Domínguez Rojas Jesús , Parra-Nigañez Patricia , Velasco-Hidalgo Liliana , Arias Sergio , Gutiérrez-Rivera Lourdes , Juárez-Villegas Luis , Márquez-González Horacio
Published: August 2022

The new COVID-19 disease is caused by a novel coronavirus (SARS-CoV-2), that probably originated in Wuhan, China, and has currently infected 505,817,953 people and caused 6,213,876 deaths in the world. On the American continent, 152,265,980 cases and 2,717,108 deaths have been reported to WHO (World Health Organization). The Latin America and the Caribbean (LAC) region presents an epidemiological challenge due to its population's heterogeneity and socioeconomic inequality. A particularly vulnerable population is that of children with cancer, and their mortality from COVID-19 has been reported to be 3.6% globally. This work aimed to study the lethality of SARS-CoV-2 infection in children with cancer in the Latin American region. Our objective was to systematically review published scientific literature and search hospital databases in Latin America to explore mortality in this region. A median of mortality of 9.8% was found in the articles analyzed. In addition, we collected five databases from Latin American hospitals. We concluded that there was an underestimation in the mortality registry of this group of patients in the analyzed region. Therefore, although the causes are unknown, it is necessary to strengthen the case-reporting system to determine the reality in complex and particular areas such as Latin America.
Plant-derived bioactive compounds regulate the NLRP3 inflammasome to treat NAFLD
Authors: Huang Qian , Xin Xin , Sun QinMei , An Ziming , Gou Xiaojun , Feng Qin
Published: August 2022

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by abnormal accumulation of hepatic fat and inflammatory response with complex pathogenesis. Over activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the secretion of interleukin (IL)-1β and IL-18, induces pyroptosis, and promotes the release of a large number of pro-inflammatory proteins. All of which contribute to the development of NAFLD. There is a great deal of evidence indicating that plant-derived active ingredients are effective and safe for NAFLD management. This review aims to summarize the research progress of 31 active plant-derived components (terpenoids, flavonoids, alkaloids, and phenols) that alleviate lipid deposition, inflammation, and pyroptosis by acting on the NLRP3 inflammasome studied in both in vitro and in vivo NAFLD models. These studies confirmed that the NLRP3 inflammasome and its related genes play a key role in NAFLD amelioration, providing a starting point for further study on the correlation of plant-derived compounds treatment with the NLRP3 inflammasome and NAFLD.
Therapeutic mechanism of Curcuma aromatica Salisb. rhizome against coronary heart disease based on integrated network pharmacology, pharmacological evaluation and lipidomics
Authors: Fei Chenghao , Ji De , Tong Huangjin , Li Yu , Su Lianlin , Qin Yuwen , Bian Zhenhua , Zhang Wei , Mao Chunqin , Li Lin , Lu Tulin
Published: August 2022

Curcuma aromatica Salisb. rhizome (CASR) has multifunctional characteristics worldwide and a long history of use as a botanical drug with. Currently, it is often used clinically to treat coronary heart disease (CHD) caused by blood stasis syndrome. However, the therapeutic mechanism of CASR in the treatment of CHD remains poorly understood. In study, the main chemical constituents of CASR were analyzed using UPLC-Q-TOF-MS/MS. Then, its potential therapeutic mechanism against CHD was predicted. Subsequently, pharmacological evaluation was performed using CHD rat model. Finally, a lipidomics approach was applied to explore the different lipid metabolites to verify the regulation of CASR on lipid metabolism disorders in CHD. A total of 35 compounds was identified from CASR. Seventeen active components and 51 potential targets related to CHD were screened by network pharmacology, involving 13 key pathways. In vivo experiments showed that CASR could significantly improve myocardial infarction, blood stasis, and blood lipid levels and regulate the PI3K/AKT/mTOR signaling pathway in CHD rats. Lipidomics further showed that CASR could regulate abnormal sphingolipid, glycerophospholipid, and glycerolipid metabolism in CHD rats. The therapeutic mechanism of CASR against CHD was initially elucidated and included the regulation of lipid metabolism. Its effects may be attributed to active ingredients, such as curzerene, isoprocurcumenol, and (+)-curcumenol. This study reveals the characteristics of multi-component and multi-pathway of CASR in the treatment of CHD, which provides a basis for the follow-up development and utilization of CASR.
Identification of molecular patterns and prognostic models of epithelial–mesenchymal transition- and immune-combined index in the gastric cancer
Authors: Zhang Xiuyuan , Li Yiming , Hu Pengbo , Xu Liang , Qiu Hong
Published: August 2022

Background: Epithelial–mesenchymal transition (EMT) and the immune microenvironment play important roles in the progression of gastric cancer (GC), but the joint role of both in GC is not clear.

Methods: We identified EMT- and immune-related genes (EIRGs), and the molecular subtypes of EIRGs were identified by unsupervised cluster analysis. Then, we constructed an accurate EIRG_score model by using differential genes of molecular subtypes. The correlation of EIRG_score with prognosis, immune infiltration, gene mutation, chemotherapeutic drug sensitivity, and immunotherapy response was comprehensively analyzed. In addition, we investigated the biological function of EIRG_score via in vitro experiments.

Results: A total of 808 GC patients were classified into two molecular subtypes, which were enriched in EMT and immune-related biological pathways and significantly correlated with prognosis and immune infiltration. The constructed EIRG_score had an important role in predicting prognosis and immunotherapeutic response. The higher EIRG_score was associated with worse prognosis, higher abundance of immunosuppressive cell infiltration, lower immune checkpoint genes expression, lower tumor mutation burden, microsatellite instability-high, lower chemotherapeutic drug sensitivity, and poorer immunotherapeutic response.

Conclusion: EIRG_score may be used as a biomarker to assess prognosis and guide precise treatment.
Traditional Chinese herbs and natural products in hyperuricemia-induced chronic kidney disease
Authors: Yang Letian , Wang Bo , Ma Liang , Fu Ping
Published: August 2022

Hyperuricemia is a common biochemical disorder, which resulted from both excessive uric acid (UA) production and/or absolute or relative impairment of urinary UA excretion. Growing evidence has indicated that hyperuricemia is an independent risk factor for the development and progression of chronic kidney disease (CKD), causing hyperuricemia-induced CKD (hyperuricemic nephropathy, HN). The therapeutic strategy of HN is managing hyperuricemia and protecting kidney function. Adverse effects of commercial drugs make persistent treatment of HN challenging. Traditional Chinese medicine (TCM) has exact efficacy in lowering serum UA without serious adverse effects. In addition, TCM is widely applied for the treatment of CKD. This review aimed to provide an overview of efficacy and mechanisms of traditional Chinese herbs and natural products in hyperuricemia-induced CKD.
Boron adatom adsorption on graphene: A case study in computational chemistry methods for surface interactions
Authors: Jubin Sierra , Rau Aaditya , Barsukov Yuri , Ethier Stephane , Kaganovich Igor
Published: August 2022

Though weak surface interactions and adsorption can play an important role in plasma processing and materials science, they are not necessarily simple to model. A boron adatom adsorbed on a graphene sheet serves as a case study for how carefully one must select the correct technique from a toolbox of computational chemistry methods. Using a variety of molecular dynamics potentials and density functional theory functionals, we evaluate the adsorption energy, investigate barriers to adsorption and migration, calculate corresponding reaction rates, and show that a surprisingly high level of theory may be necessary to verify that the system is described correctly.
Implementation of exercise countermeasures during spaceflight and microgravity analogue studies: Developing countermeasure protocols for bedrest in older adults (BROA)
Authors: Hedge Eric T. , Patterson Courtney A. , Mastrandrea Carmelo J. , Sonjak Vita , Hajj-Boutros Guy , Faust Andréa , Morais José A. , Hughson Richard L.
Published: August 2022

Significant progress has been made in the development of countermeasures to attenuate the negative consequences of prolonged exposure to microgravity on astronauts’ bodies. Deconditioning of several organ systems during flight includes losses to cardiorespiratory fitness, muscle mass, bone density and strength. Similar deconditioning also occurs during prolonged bedrest; any protracted time immobile or inactive, especially for unwell older adults (e.g., confined to hospital beds), can lead to similar detrimental health consequences. Due to limitations in physiological research in space, the six-degree head-down tilt bedrest protocol was developed as ground-based analogue to spaceflight. A variety of exercise countermeasures have been tested as interventions to limit detrimental changes and physiological deconditioning of the musculoskeletal and cardiovascular systems. The Canadian Institutes of Health Research and the Canadian Space Agency recently provided funding for research focused on Understanding the Health Impact of Inactivity to study the efficacy of exercise countermeasures in a 14-day randomized clinical trial of six-degree head-down tilt bedrest study in older adults aged 55–65 years old (BROA). Here we will describe the development of a multi-modality countermeasure protocol for the BROA campaign that includes upper- and lower-body resistance exercise and head-down tilt cycle ergometry (high-intensity interval and continuous aerobic exercise training). We provide reasoning for the choice of these modalities following review of the latest available information on exercise as a countermeasure for inactivity and spaceflight-related deconditioning. In summary, this paper sets out to review up-to-date exercise countermeasure research from spaceflight and head-down bedrest studies, whilst providing support for the proposed research countermeasure protocols developed for the bedrest study in older adults.
Optimization of quantitative reverse transcription PCR method for analysis of weakly expressed genes in crops based on rapeseed
Authors: Moebes Michael , Kuhlmann Heike , Demidov Dmitri , Lermontova Inna
Published: August 2022

Rapeseed (Brassica napus) is an allopolyploid hybrid (AACC genome) of turnip rape (B. rapa, genome: AA) and vegetable cabbage (B. oleraceae, genome: CC). Rapeseed oil is one of the main vegetable oils used worldwide for food and other technical purposes. Therefore, breeding companies worldwide are interested in developing rapeseed varieties with high yields and increased adaptation to harsh climatic conditions such as heat and prolonged drought. One approach to studying the mechanism of the epigenetically regulated stress response is to analyze the transcriptional changes it causes. In addition, comparing the expression of certain genes between stress- and non-stress-tolerant varieties will help guide breeding in the desired direction. Quantitative reverse transcription PCR (RT-qPCR) has been intensively used for gene expression analysis for several decades. However, the transfer of this method from model plants to crop species has several limitations due to the high accumulation of secondary metabolites, the higher water content in some tissues and therefore problems with their grinding and other factors. For allopolyploid rapeseed, the presence of two genomes, often with different levels of expression of homeologous genes, must also be considered. In this study, we describe the optimization of transcriptional RT-qPCR analysis of low-expression epigenetic genes in rapeseed, using Kinetochore Null2 (KNL2), a regulator of kinetochore complex assembly, as an example. We demonstrated that a combination of various factors, such as tissue homogenization and RNA extraction with TRIzol, synthesis of cDNA with gene-specific primers, and RT-qPCR in white plates, significantly increased the sensitivity of RT-qPCR for the detection of BnKNL2A and BnKNL2C gene expression.