bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyanoremediation and phyconanotechnology: cyanobacteria for metal biosorption toward a circular economy
Authors: Ciani Matilde , Adessi Alessandra
Published: May 2023

Cyanobacteria are widespread phototrophic microorganisms that represent a promising biotechnological tool to satisfy current sustainability and circularity requirements. They are potential bio-factories of a wide range of compounds that can be exploited in several fields including bioremediation and nanotechnology sectors. This article aims to illustrate the most recent trends in the use of cyanobacteria for the bioremoval (i.e., cyanoremediation) of heavy metals and metal recovery and reuse. Heavy metal biosorption by cyanobacteria can be combined with the consecutive valorization of the obtained metal-organic materials to get added-value compounds, including metal nanoparticles, opening the field of phyconanotechnology. It is thus possible that the use of combined approaches could increase the environmental and economic feasibility of cyanobacteria-based processes, promoting the transition toward a circular economy.
The XBB.1.5 slightly increase the binding affinity for host receptor ACE2 and exhibit strongest immune escaping features: molecular modeling and free energy calculation
Authors: Suleman Muhammad , Murtaza Aneela , Khan Haji , Rashid Farooq , Alshammari Abdulrahman , Ali Liaqat , Khan Abbas , Wei Dong-Qing ,   Maria
Published: May 2023

Introduction: The current XBB variant of SARS-CoV-2 with the strongest immune escaping properties is currently the most dominant variant circulating around the world. With the emergence of XBB global morbidities and mortalities have raised again. In the current scenario, it was highly required to delineate the binding capabilities of NTD of XBB subvariant towards human neutralizing antibodies and to dig out the binding affinity of RBD of XBB subvariant with ACE2 receptor.

Materials and Methods: The current study uses molecular interaction and simulation-based approaches to decipher the binding mechanism of RBD with ACE2 and mAb interaction with NTD of the spike protein.

Results: Molecular docking of the Wild type NTD with mAb revealed a docking score of −113.2 ± 0.7 kcal/mol while XBB NTD docking with mAb reported −76.2 ± 2.3 kcal/mol. On the other hand, wild-type RBD and XBB RBD with ACE2 receptor demonstrated docking scores of −115.0 ± 1.5 kcal/mol and −120.8 ± 3.4 kcal/mol respectively. Moreover, the interaction network analysis also revealed significant variations in the number of hydrogen bonds, salt-bridges, and non-bonded contacts. These findings were further validated by computing the dissociation constant (KD). Molecular simulation analysis such as RMSD, RMSF, Rg and hydrogen bonding analysis revealed variation in the dynamics features of the RBD and NTD complexes due to the acquired mutations. Furthermore, the total binding energy for the wild-type RBD in complex with ACE2 reported −50.10 kcal/mol while XBB-RBD coupled with ACE2 reported −52.66 kcal/mol respectively. This shows though the binding of XBB is slightly increased but due to the variation in the bonding network and other factors makes the XBB variant to enter into the host cell efficiently than the wild type. On the other hand, the total binding free energy for the wildtype NTD-mAb was calculated to be −65.94 kcal/mol while for XBB NTD-mAb was reported to be −35.06 kcal/mol respectively. The significant difference in the total binding energy factors explains that the XBB variant possess stronger immune evasion properties than the others variants and wild type.

Conclusions: The current study provides structural features for the XBB variant binding and immune evasion which can be used to design novel therapeutics.
Long non-coding RNA lncMGC mediates the expression of TGF-β-induced genes in renal cells via nucleosome remodelers
Authors: Kato Mitsuo , Chen Zhuo , Das Sadhan , Wu Xiwei , Wang Jinhui , Li Arthur , Chen Wei , Tsark Walter , Tunduguru Ragadeepthi , Lanting Linda , Wang Mei , Moore Roger , Kalkum Markus , Abdollahi Maryam , Natarajan Rama
Published: May 2023

Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play key roles in diabetic kidney disease (DKD). The miR-379 megacluster of miRNAs and its host transcript lnc-megacluster (lncMGC) are regulated by transforming growth factor-β (TGF-β), increased in the glomeruli of diabetic mice, and promote features of early DKD. However, biochemical functions of lncMGC are unknown. Here, we identified lncMGC-interacting proteins by in vitro-transcribed lncMGC RNA pull down followed by mass spectrometry. We also created lncMGC-knockout (KO) mice by CRISPR-Cas9 editing and used primary mouse mesangial cells (MMCs) from the KO mice to examine the effects of lncMGC on the gene expression related to DKD, changes in promoter histone modifications, and chromatin remodeling.

Methods:In vitro-transcribed lncMGC RNA was mixed with lysates from HK2 cells (human kidney cell line). lncMGC-interacting proteins were identified by mass spectrometry. Candidate proteins were confirmed by RNA immunoprecipitation followed by qPCR. Cas9 and guide RNAs were injected into mouse eggs to create lncMGC-KO mice. Wild-type (WT) and lncMGC-KO MMCs were treated with TGF-β, and RNA expression (by RNA-seq and qPCR) and histone modifications (by chromatin immunoprecipitation) and chromatin remodeling/open chromatin (by Assay for Transposase-Accessible Chromatin using sequencing, ATAC-seq) were examined.

Results: Several nucleosome remodeling factors including SMARCA5 and SMARCC2 were identified as lncMGC-interacting proteins by mass spectrometry, and confirmed by RNA immunoprecipitation–qPCR. MMCs from lncMGC-KO mice showed no basal or TGF-β-induced expression of lncMGC. Enrichment of histone H3K27 acetylation and SMARCA5 at the lncMGC promoter was increased in TGF-β-treated WT MMCs but significantly reduced in lncMGC-KO MMCs. ATAC peaks at the lncMGC promoter region and many other DKD-related loci including Col4a3 and Col4a4 were significantly lower in lncMGC-KO MMCs compared to WT MMCs in the TGF-β-treated condition. Zinc finger (ZF), ARID, and SMAD motifs were enriched in ATAC peaks. ZF and ARID sites were also found in the lncMGC gene.

Conclusion: lncMGC RNA interacts with several nucleosome remodeling factors to promote chromatin relaxation and enhance the expression of lncMGC itself and other genes including pro-fibrotic genes. The lncMGC/nucleosome remodeler complex promotes site-specific chromatin accessibility to enhance DKD-related genes in target kidney cells.
The endogenous cannabinoid system modulates male sexual behavior expression
Authors: Rodríguez-Manzo Gabriela , Canseco-Alba Ana
Published: May 2023

The endocannabinoid system (ECS) plays a key neuromodulatory role in the brain. Main features of endocannabinoids (eCBs) are that they are produced on demand, in response to enhanced neuronal activity, act as retrograde messengers, and participate in the induction of brain plasticity processes. Sexual activity is a motivated behavior and therefore, the mesolimbic dopaminergic system (MSL) plays a central role in the control of its appetitive component (drive to engage in copulation). In turn, copulation activates mesolimbic dopamine neurons and repeated copulation produces the continuous activation of the MSL system. Sustained sexual activity leads to the achievement of sexual satiety, which main outcome is the transient transformation of sexually active male rats into sexually inhibited animals. Thus, 24 h after copulation to satiety, the sexually satiated males exhibit a decreased sexual motivation and do not respond to the presence of a sexually receptive female with sexual activity. Interestingly, blockade of cannabinoid receptor 1 (CB1R) during the copulation to satiety process, interferes with both the appearance of the long-lasting sexual inhibition and the decrease in sexual motivation in the sexually satiated males. This effect is reproduced when blocking CB1R at the ventral tegmental area evidencing the involvement of MSL eCBs in the induction of this sexual inhibitory state. Here we review the available evidence regarding the effects of cannabinoids, including exogenously administered eCBs, on male rodent sexual behavior of both sexually competent animals and rat sub populations spontaneously showing copulatory deficits, considered useful to model some human male sexual dysfunctions. We also include the effects of cannabis preparations on human male sexual activity. Finally, we review the role played by the ECS in the control of male sexual behavior expression with the aid of the sexual satiety phenomenon. Sexual satiety appears as a suitable model for the study of the relationship between eCB signaling, MSL synaptic plasticity and the modulation of male sexual motivation under physiological conditions that might be useful for the understanding of MSL functioning, eCB-mediated plasticity and their relationship with motivational processes.
Moderate-to-high risk of obstructive sleep apnea with excessive daytime sleepiness is associated with postoperative neurocognitive disorders: a prospective one-year follow-up cohort study
Authors: Wu Wenwen , Pu Lihui , Hu Xiuying , Chen Qian , Wang Guan , Wang Yanyan
Published: May 2023

Background

Few studies found that obstructive sleep apnea (OSA) may be related to postoperative neurocognitive disorders (PND) including postoperative delirium (POD) and cognitive decline (POCD) in the early postoperative period. However, the results are controversial and need further verification, and no research has explored the effect of OSA on the incidence of PND during the 1-year follow-up periods. Furthermore, OSA patients with excessive daytime sleepiness (EDS) as a severe phenotype have more significant neurocognitive impairments, but the relationship between OSA with EDS and PND within 1 year after surgery has not been studied.

Objectives

To explore the effect of moderate-to-high risk of OSA and the moderate-to-high risk of OSA with EDS on PND within 1 year after surgery.

Methods

In this prospective cohort study, including 227 older patients, moderate-to-high risk of OSA (using STOP-BANG), subjective EDS (using Epworth Sleepiness Scale), and objective EDS (using Actigraphy) were selected as exposures. Key outcomes included POD during hospitalization (using Confusion Assessment Method-Severity), POCD at discharge, 1-month and 1-year after surgery (using Mini-Mental State Examination and Telephone Interview for Cognitive Status-40). We applied multiple logistic regression models to estimate the effect of moderate-to-high risk of OSA and moderate-to-high risk of OSA with EDS on PND.

Results

In the multivariate analysis, moderate-to-high risk of OSA was not associated with POD during hospitalization and POCD at discharge, 1-month, and 1-year after surgery (p > 0.05). However, the moderate-to-high risk of OSA with subjective EDS was related to POCD at discharge compared to the moderate-to-high risk of OSA or normal group (no moderate-to-high risk of OSA and no EDS) (p < 0.05). In addition, moderate-to-high risk of OSA with objective EDS was associated with POCD at discharge, 1-month, and 1-year postoperatively compared to the moderate-to-high risk of OSA or normal group (p < 0.05).

Conclusion

Moderate-to-high risk of OSA with EDS, not moderate-to-high risk of OSA alone, was a clinically helpful predictor for POCD within 1-year after surgery and should be routinely assessed before surgery.
Hydrogel scaffolds in the treatment of spinal cord injury: a review
Authors: Cai Manqi , Chen Liji , Wang Tao , Liang Yinru , Zhao Jie , Zhang Xiaomin , Li Ziyi , Wu Hongfu
Published: May 2023

Spinal cord injury (SCI) is a disease of the central nervous system often caused by accidents, and its prognosis is unsatisfactory, with long-term adverse effects on patients’ lives. The key to its treatment lies in the improvement of the microenvironment at the injury and the reconstruction of axons, and tissue repair is a promising therapeutic strategy. Hydrogel is a three-dimensional mesh structure with high water content, which has the advantages of biocompatibility, degradability, and adjustability, and can be used to fill pathological defects by injectable flowing hydrophilic material in situ to accurately adapt to the size and shape of the injury. Hydrogels mimic the natural extracellular matrix for cell colonization, guide axon extension, and act as a biological scaffold, which can be used as an excellent carrier to participate in the treatment of SCI. The addition of different materials to make composite hydrogel scaffolds can further enhance their performance in all aspects. In this paper, we introduce several typical composite hydrogels and review the research progress of hydrogel for SCI to provide a reference for the clinical application of hydrogel therapy for SCI.
The recurrent pathogenic Pro890Leu substitution in CLTC causes a generalized defect in synaptic transmission in Caenorhabditis elegans
Authors: Pannone Luca , Muto Valentina , Nardecchia Francesca , Di Rocco Martina , Marchei Emilia , Tosato Federica , Petrini Stefania , Onorato Giada , Lanza Enrico , Bertuccini Lucia , Manti Filippo , Folli Viola , Galosi Serena , Di Schiavi Elia , Leuzzi Vincenzo , Tartaglia Marco , Martinelli Simone
Published: May 2023

De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c.2669C > T (p.P890L) substitution, which is associated with a relatively mild ID/MD phenotype. Primary fibroblasts endogenously expressing the mutated protein show reduced transferrin uptake compared to fibroblast lines obtained from three unrelated healthy donors, suggesting defective clathrin-mediated endocytosis. In vitro studies also reveal a block in cell cycle transition from G0/G1 to the S phase in patient’s cells compared to control cells. To demonstrate the causative role of the p.P890L substitution, the pathogenic missense change was introduced at the orthologous position of the Caenorhabditis elegans gene, chc-1 (p.P892L), via CRISPR/Cas9. The resulting homozygous gene-edited strain displays resistance to aldicarb and hypersensitivity to PTZ, indicating defective release of acetylcholine and GABA by ventral cord motor neurons. Consistently, mutant animals show synaptic vesicle depletion at the sublateral nerve cords, and slightly defective dopamine signaling, highlighting a generalized deficit in synaptic transmission. This defective release of neurotransmitters is associated with their secondary accumulation at the presynaptic membrane. Automated analysis of C. elegans locomotion indicates that chc-1 mutants move slower than their isogenic controls and display defective synaptic plasticity. Phenotypic profiling of chc-1 (+/P892L) heterozygous animals and transgenic overexpression experiments document a mild dominant-negative behavior for the mutant allele. Finally, a more severe phenotype resembling that of chc-1 null mutants is observed in animals harboring the c.3146 T > C substitution (p.L1049P), homologs of the pathogenic c.3140 T > C (p.L1047P) change associated with a severe epileptic phenotype. Overall, our findings provide novel insights into disease mechanisms and genotype–phenotype correlations of CLTC-related disorders.
Anthocyanin-rich blue potato meals protect against polychlorinated biphenyl-mediated disruption of short-chain fatty acid production and gut microbiota profiles in a simulated human digestion model
Authors: Lu Fang , MacPherson Chad W. , Tremblay Julien , Iskandar Michèle M. , Kubow Stan
Published: May 2023

Background

Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants associated with a wide variety of adverse human health outcomes. PCB 126 and PCB 153 are among the most prevalent congeners associated with human exposure. Emerging studies have suggested that PCB exposure leads to lower gut microbial diversity although their effects on microbial production of health promoting short-chain fatty acids (SCFAs) has been scarcely studied. Blue potatoes are rich in anthocyanins (ACNs), which is a class of polyphenols that promote the growth of beneficial intestinal bacteria such as Bifidobacterium and Lactobacillus and increase the generation of SCFAs. A batch-culture, pH-controlled, stirred system containing human fecal microbial communities was utilized to assess whether human gut microbiota composition and SCFA production are affected by: (a) PCB 126 and PCB 153 exposure; and (b) ACN-rich digests in the presence and absence of the PCB congeners.

Methods

Anthocyanin-rich blue potato meals (11.03 g) were digested over 12 h with and without PCB 126 (0.5 mM) and PCB 153 (0.5 mM) using an in vitro simulated gut digestion model involving upper gastrointestinal digestion followed by metabolism by human fecal microbiota. Fecal digests were collected for analysis of gut microbial and SCFA profiles.

Results

Polychlorinated biphenyl-exposed fecal samples showed a significant (p < 0.05) decrease in species richness and a significantly (p < 0.05) different microbial community structure. PCB treatment was associated with an increased (p < 0.05) relative abundance of Akkermansia, Eggerthella, and Bifidobacterium and a decreased (p < 0.05) relative abundance of Veillonella, Streptococcus, and Holdemanella. ACN digests counteracted the altered abundances of Akkermansia and Bifidobacterium seen with the PCB treatment. PCB exposure was associated with a significant (p < 0.05) decrease in total SCFA and acetate concentrations. ACN digests were associated with significantly (p < 0.05) higher SCFA and acetate concentrations in the presence and absence of PCBs.

Conclusion

Human fecal matter exposed to PCB 126 and PCB 153 led to decreased abundance and altered gut microbiota profiles as well as lowered SCFA and acetate levels. Importantly, this study showed that prebiotic ACN-rich potatoes counteract PCB-mediated disruptions in human gut microbiota profiles and SCFA production.
Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort
Authors: Doppenberg D. , Lagerwaard F. J. , van Dieren S. , Meijerink M. R. , van der Vliet J. J. , Besselink M. G. , van Tienhoven G. , Versteijne E. , Slotman B. J. , Wilmink J. W. , Kazemier G. , Bruynzeel A. M. E.
Published: May 2023

Background

The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking.

Methods

A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS.

Results

Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%.

Conclusions

SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings.
Efficacy and safety of third-line or later-line targeted treatment for patients with metastatic colorectal cancer: a meta-analysis
Authors: Xue Wen-Hui , Li Xue-Wei , Ding Ya-Qian , Wu Na , Pei Bei-Bei , Ma Xiao-Yan , Xie Jun , Yang Wen-Hui
Published: May 2023

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.
Comprehensive analysis of the prognosis and immune effect of the oncogenic protein Four Jointed Box 1
Authors: Huang Mei , Guo Tian , Meng Yan , Zhou Ruling , Xiong Man , Ding Jian , Zhang Yali , Liu Side , Zhuang Kangmin
Published: May 2023

Background

The Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene.

Methods

We analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration through in vitro functional experiments.

Results

Our study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration.

Conclusion

Our research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer.
Afatinib combined with anti-PD1 enhances immunotherapy of hepatocellular carcinoma via ERBB2/STAT3/PD-L1 signaling
Authors: Yu Chao , Zhang Xinyi , Wang Min , Xu Gaoxin , Zhao Siqi , Feng Yongheng , Pan Chao , Yang Weijun , Zhou Jin , Shang Longcheng , Ma Yong
Published: May 2023

Background

Afatinib is mainly used to treat advanced non-small cell lung cancer, but its therapeutic effect on hepatocellular carcinoma is still unclear.

Methods

Over 800 drugs were screened by CCK8 technology and afatinib was found to have a significant inhibitory effect on liver cancer cells. The expression of PDL1 in tumor cells treated with drugs were detected by qRT-PCR and Weston Blot experiments. The effects of afatinib on the growth, migration and invasion of HCC cells were evaluated using wound healing, Transwell, and cell cloning assays. The in vivo effects of afatinib in combination with anti-PD1 were evaluated in C57/BL6J mice with subcutaneous tumorigenesis. Bioinformatics analysis was performed to explore the specific mechanism of afatinib's inhibition of ERBB2 in improving the expression level of PD-L1, which was subsequently verified through experiments.

Results

Afatinib was found to have a significant inhibitory effect on liver cancer cells, as confirmed by in vitro experiments, which demonstrated that it could significantly suppress the growth, invasion and migration of HCC cells. qRT PCR and Weston Blot experiments also showed that Afatinib can enhance the expression of PD-L1 in tumor cells. In addition, in vitro experiments confirmed that afatinib can significantly enhance the immunotherapeutic effect of hepatocellular carcinoma. Afatinib’s ability to increase PD-L1 expression is mediated by STAT3 activation following its action on HCC cells.

Conclusion

Afatinib enhances PD-L1 expression in tumor cells through the STAT3/PD-L1 pathway. The combination of afatinib and anti-PD1 treatment significantly increases the immunotherapeutic effect of HCC.
Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis
Authors: Altaf Reem , Ilyas Umair , Ma Anmei , Shi Meiqi
Published: May 2023

Background

Despite the high prevalence of lung cancer, with a five-year survival rate of only 23%, the underlying molecular mechanisms of non-small cell lung cancer (NSCLC) remain unknown. There is a great need to identify reliable candidate biomarker genes for early diagnosis and targeted therapeutic strategies to prevent cancer progression.

Methods

In this study, four datasets obtained from the Gene Expression Omnibus were evaluated for NSCLC- associated differentially expressed genes (DEGs) using bioinformatics analysis. About 10 common significant DEGs were shortlisted based on their p-value and FDR (DOCK4, ID2, SASH1, NPR1, GJA4, TBX2, CD24, HBEGF, GATA3, and DDR1). The expression of significant genes was validated using experimental data obtained from TCGA and the Human Protein Atlas database. The human proteomic data for post- translational modifications was used to interpret the mutations in these genes.

Results

Validation of DEGs revealed a significant difference in the expression of hub genes in normal and tumor tissues. Mutation analysis revealed 22.69%, 48.95%, and 47.21% sequence predicted disordered regions of DOCK4, GJA4, and HBEGF, respectively. The gene-gene and drug-gene network analysis revealed important interactions between genes and chemicals suggesting they could act as probable drug targets. The system-level network showed important interactions between these genes, and the drug interaction network showed that these genes are affected by several types of chemicals that could serve as potential drug targets.

Conclusions

The study demonstrates the importance of systemic genetics in identifying potential drug- targeted therapies for NSCLC. The integrative system- level approach should contribute to a better understanding of disease etiology and may accelerate drug discovery for many cancer types.
Surgical treatment of a distal radius and ipsilateral metacarpal hemophilic pseudotumor without recurrence or functional deficit: a case report
Authors: Wang Yingjie , Lv Zehui , Dong Xiying , Feng Bin , Weng Xisheng
Published: May 2023

Background

Distal hemophilic pseudotumor (HP) occurring distal to the wrist appear to be secondary to intraosseous hemorrhage, which develops rapidly and should be treated primarily with long-term replacement therapy and cast immobilization. Surgical removal or even amputation is indicated when conservative management fails to prevent progression. Here, a practical strategy was described for those patients who cannot afford the cost of routine coagulation factor replacement therapy, namely immediate surgical curettage and bone grafting as well as continuous follow-up.

Case description

A 7-year-old boy with a history of mild hemophilia A was admitted to our medical center because of a 2-year history of progressive swelling and pain around right forearm and hand. Coagulation factor VIII level was 11.1% of normal with no inhibitor. Radiographs revealed expansile swelling, bone destruction, and deformity of the distal right radius and the second metacarpal bone. He was diagnosed with distal HP. Surgical procedure of curettage and bone grafting was performed. The function and appearance of the right wrist were almost normal without discomfort at the 101-month follow-up. Significantly, the same patient was hospitalized again because of a year-long progressive swelling and pain around the left hand when he was 14 years old. X-ray showed multiple bone destruction of the left proximal phalanges of left thumb, middle finger and little finger with local pathological fractures. Surgical procedure of HPs including curettage and bone grafting was performed. Postoperative recovery was good, and the last clinical follow-up at 18 months after the operation displayed a satisfactory shape and functional outcomes.

Conclusions

Curettage and bone grafting prove to be safe and feasible for patients with distal HP and continuous follow-up of patients with distal HP is very vital for timely finding and then treating successive HP in developing countries.
Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant
Authors: Lemoine Caroline P. , Brandt Katherine A. , Keswani Mahima , Superina Riccardo
Published: May 2023

Background

ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis.

Methods

A retrospective review of all patients who received an ABOi LT at our institution was performed. Comparisons were made based on era (early: 1997–2008, modern: 2009–2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant.

Results

17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1–28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1.

Conclusion

ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.
Vitreoretinal biomarkers of retinopathy of prematurity using handheld optical coherence tomography: a review
Authors: Kubsad Deepika , Ohan Masis A. , Wu Jolan G. , Cabrera Michelle T.
Published: May 2023

Retinopathy of prematurity (ROP) is caused by abnormal retinal vascularization in premature infants that has the potential for severe long-term vision impairment. Recent advancements in handheld optical coherence tomography (OCT) have enabled noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. The use of handheld OCT devices in the diagnosis of ROP in premature infants has furthered our understanding of disease state and progression. This review discusses the known and novel biomarkers of ROP severity in premature infants identified through handheld OCT and potential for future directions.
Gut microbial composition and functionality of school-age Mexican population with metabolic syndrome and type-2 diabetes mellitus using shotgun metagenomic sequencing
Authors: Carrizales-Sánchez Ana K. , Tamez-Rivera Oscar , García-Gamboa Ricardo , García-Cayuela Tomás , Rodríguez-Gutiérrez Nora A , Elizondo-Montemayor Leticia , García-Rivas Gerardo , Pacheco Adriana , Hernández-Brenes Carmen , Senés-Guerrero Carolina
Published: May 2023

Gut metagenome in pediatric subjects with metabolic syndrome (MetS) and type-2 diabetes mellitus (T2DM) has been poorly studied, despite an alarming worldwide increase in the prevalence and incidence of obesity and MetS within this population. The objective of this study was to characterize the gut microbiome taxonomic composition of Mexican pediatric subjects with MetS and T2DM using shotgun metagenomics and analyze the potential relationship with metabolic changes and proinflammatory effects. Paired-end reads of fecal DNA samples were obtained through the Illumina HiSeq X Platform. Statistical analyses and correlational studies were conducted using gut microbiome data and metadata from all individuals. Gut microbial dysbiosis was observed in MetS and T2DM children compared to healthy subjects, which was characterized by an increase in facultative anaerobes (i.e., enteric and lactic acid bacteria) and a decrease in strict anaerobes (i.e., Erysipelatoclostridium, Shaalia, and Actinomyces genera). This may cause a loss of gut hypoxic environment, increased gut microbial nitrogen metabolism, and higher production of pathogen-associated molecular patterns. These metabolic changes may trigger the activation of proinflammatory activity and impair the host's intermediate metabolism, leading to a possible progression of the characteristic risk factors of MetS and T2DM, such as insulin resistance, dyslipidemia, and an increased abdominal circumference. Furthermore, specific viruses (Jiaodavirus genus and Inoviridae family) showed positive correlations with proinflammatory cytokines involved in these metabolic diseases. This study provides novel evidence for the characterization of MetS and T2DM pediatric subjects in which the whole gut microbial composition has been characterized. Additionally, it describes specific gut microorganisms with functional changes that may influence the onset of relevant health risk factors.
Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies
Authors: Theron A. , Ayadi S. , Boissier E. , Dautremay O. , Schved J.-F. , Sirvent N. , Diaz I. , Captier G. , Biron-Andreani C. , Jeziorski E.
Published: May 2023

Introduction

Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication.

Method

This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aβ2GP1).

Results

Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aβ2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37–1.71], p = 1 and RR: 0.7 [95% CI: 0.33–1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.
Ginkgolide With Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function: A Multicenter, Cluster-Randomized Trial (GIANT)
Authors: Zhang Xuting , Zhong Wansi , Ma Xiaodong , Zhang Xiaoling , Chen Hongfang , Wang Zhimin , Lou Min , GIANT Investigators
Published: May 2023

Background and Purpose: We aimed to investigate the effect of Ginkgolide® treatment on neurological function in patients receiving intravenous (IV) recombinant tissue plasminogen activator (rt-PA).

Methods: This cluster randomized controlled trial included acute ischemic stroke patients in 24 centers randomized to intervention of intravenous Ginkgolide® or control group within the first 24 h after IV rt-PA therapy (IVT). Clinical outcome at 90 days was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0–2) and poor outcome (3–6). Hemorrhagic transformation represented the conversion of a bland infarction into an area of hemorrhage by computed tomography. Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 7-day or if the hemorrhage was likely to be the cause of the clinical deterioration. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of Ginkgolide® treatment with IV rt-PA on good outcome, hemorrhagic transformation and sICH, respectively.

Results: A total of 1113 patients were finally included and 513 (46.1%) were in the intervention group. Patients in the Ginkgolide® group were more likely to have good outcomes (78.6 vs. 66.7%, p < 0.01) and lower rate of sICH (0 vs. 2.72%, p < 0.01), compared with patients in the control group. The intra-cluster correlation coefficient (ICC) for good outcome at 90 days was 0.033. Binary logistic regression analysis revealed that treatment with Ginkgolide® was independently associated with 90-day mRS in patients with IV rt-PA therapy (OR 1.498; 95% CI 1.006–2.029, p = 0.009). After propensity score matching, conditional logistic regression showed intervention with Ginkgolide® was significantly associated with 90-day good outcome (OR 1.513; 95% CI 1.073–2.132, p = 0.018). No significant difference in hemorrhage transformation was seen between the 2 matched cohorts (OR 0.885; 95% CI 0.450–1.741, p = 0.724).

Conclusion: Using Ginkgolide® within 24-hour after IV rt-PA is effective and safe and might be recommended in combination with rtPA therapy in acute ischemic stroke.

Clinical Trial Registration:http://www.clinicaltrials.gov, identifier NCT03772847.
Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors
Authors: Fiedler Lukas , Motloch Lukas J. , Dieplinger Anna-Maria , Jirak Peter , Davtyan Paruir , Gareeva Diana , Badykova Elena , Badykov Marat , Lakman Irina , Agapitov Aleksandr , Sadikova Liana , Pavlov Valentin , Föttinger Fabian , Mirna Moritz , Kopp Kristen , Hoppe Uta C. , Pistulli Rudin , Cai Benzhi , Yang Baofeng , Zagidullin Naufal
Published: May 2023

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date.

Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days].

Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ2-statistics = 6.45, p = 0.013 and SCD: χ2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group.

Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.
Droplet oscillations in a turbulent flow
Authors: Roa Ignacio , Renoult Marie-Charlotte , Dumouchel Christophe , Brändle de Motta Jorge César
Published: May 2023

The oscillations of an initially unperturbed spherical droplet immersed in a homogeneous and isotropic turbulent background flow are investigated through spherical harmonic decomposition. As suggested in the literature, the shape oscillations under turbulent conditions are related to the frequency of droplets oscillating in a fluid without background flow. A series of direct numerical simulations (DNS) of droplets with single deformation modes in a fluid at rest are first performed. The frequency and damping rate are compared with weakly viscous linear theory. Then, a database of 220 droplets deformed under turbulent conditions for a single Weber and Reynolds number is generated with an identical numerical set-up. Each spherical harmonic coefficient shows an oscillatory motion with comparable frequency to the single deformation mode simulations. The power spectrum of the coefficients provides the amount of surface of each mode. After a transient regime, the surface area reaches a stationary saturation level. The saturation level of each mode is linked to the turbulence and the energy stored at the interface. Droplets after a high deformation are studied with and without background flow. As expected, the physics of relaxation is driven by capillary forces.
Graphene-coated D-shaped terahertz fiber modulator
Authors: Wang Shaona , Su Mengya , Tang Longhuang , Li Xianguo , Li Xiuyan , Bai Hua , Niu Pingjuan , Shi Jia , Yao Jianquan
Published: May 2023

A terahertz (THz) fiber is of interest due to low loss and easy beam shaping. Graphene plays an important role in modulating the optical signal. In this paper, a graphene-coated D-shaped THz fiber modulator is proposed. The performance of the proposed modulator is investigated by the finite element method. The inference of geometric parameters of the structure on the proposed modulator is also analyzed, and an optimal structure is obtained. Simulation results show that the confinement loss and the full width at half-maximum (FWHM) can be tuned by adjusting the Fermi level of graphene. The proposed THz fiber modulator shows potential in future THz fiber communications.
Pattern of the heart rate performance curve in maximal graded treadmill running from 1100 healthy 18–65 Years old men and women: the 4HAIE study
Authors: Birnbaumer Philipp , Dostal Tomas , Cipryan Lukas , Hofmann Peter
Published: May 2023

Introduction: The heart rate performance curve (HRPC) in maximal incremental cycle ergometer exercise demonstrated three different patterns such as downward, linear or inverse versions. The downward pattern was found to be the most common and therefore termed regular. These patterns were shown to differently influence exercise prescription, but no data are available for running. This study investigated the deflection of the HRPC in maximal graded treadmill tests (GXT) of the 4HAIE study.

Methods: Additional to maximal values, the first and second ventilatory thresholds as well as the degree and the direction of the HRPC deflection (kHR) were determined from 1,100 individuals (489 women) GXTs. HRPC deflection was categorized as downward (kHR < −0.1), linear (−0.1 ≤ kHR ≤ 0.1) or inverse (kHR > 0.1) curves. Four (even split) age- and two (median split) performance-groups were used to investigate the effects of age and performance on the distribution of regular (= downward deflection) and non-regular (= linear or inverse course) HR curves for male and female subjects.

Results: Men (age: 36.8 ± 11.9 years, BMI: 25.0 ± 3.3 kg m−2, VO2max: 46.4 ± 9.4 mL min−1. kg−1) and women (age: 36.2 ± 11.9 years, BMI: 23.3 ± 3.7 kg m−2, VO2max: 37.4 ± 7.8 mL min−1. kg−1) presented 556/449 (91/92%) downward deflecting, 10/8 (2/2%) linear and 45/32 (7/6%) inverse HRPC´s. Chi-squared analysis revealed a significantly higher number of non-regular HRPC´s in the low-performance group and with increasing age. Binary logistic regression revealed that the odds ratio (OR) to show a non-regular HRPC is significantly affected by maximum performance (OR = 0.840, 95% CI = 0.754–0.936, p = 0.002) and age (OR = 1.042, 95% CI = 1.020–1.064, p < 0.001) but not sex.

Discussion: As in cycle ergometer exercise, three different patterns for the HRPC were identified from the maximal graded treadmill exercise with the highest frequency of regular downward deflecting curves. Older subjects and subjects with a lower performance level had a higher probability to show a non-regular linear or inverted curve which needs to be considered for exercise prescription.