bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA Seq Analysis Reveal Differential Expression of Genes Associated With Metabolic Reprogramming, Defense and Signaling in Two Contrasting Indigenous Aromatic Rice Cultivars Differing in Redox Regulatory Properties Under Drought Stress
Authors: Dey Nivedita , Bhattacharjee Soumen
Published: January 2021

Background: Though there are at present seventy indigenous aromatic rice cultivars being cultivated in West Bengal, India, the information regarding their genetic regulation of drought tolerance are scanty. Previous work from this laboratory has screened indigenous aromatic rice cultivars Badshabhog and Jamainadu as drought tolerant redox competent and drought susceptible redox incompetent germplasms respectivelybased on redox metabolomic investigation. In this backdrop, the present work comprehended to compare two indigenous aromatic rice cultivars for unfolding genetic regulation of drought stress. Results: The result of comparative transcriptomic study through RNA-seq analysis in general revealed significant cultivar specific expression of genes under post-imbibitional dehydration stress as well as genes that are expressed in both the experimental cultivars (Oryza sativa L., cultivars Badshabhog and Jamainadu) with differential transcript abundance. 3482 and 3866 genes were found to be significantly down-regulated and up-regulated respectively when we compared between post-imbibitional dehydration stress-raised indigenous aromatic rice cultivars Badshabhog and Jamainadu. Transcripts selected for heatmap generation with proper annotation revealed 50 genes that are significantly expressed genes which are mainly involved in redox functions, signaling, membrane trafficking, replication and protein synthesis etc. On the contrary, genes which got highly expressed in Badshabhog found to be mainly concerned with carbondioxide concentrating mechanism (NADH-dependent malic enzyme), peroxysomal biogenesis, protein modification, protein synthesis, mitochondrial electron transport chain functioning, inercellular protein transport, histone demethylation associated with developmental process, regulation of apoptosis etc. Further Badshabhog exhibited greater GO (gene ontology) distribution so far as signaling, antioxidant functioning, biological and metabolic regulation, transcriptional and translational regulation etc. with significantly higher percentage of antioxidant genes. KEGG (kyoto encyclopedia of genes and genomes) pathway analysis showed several signal transduction pathways (abscisic acid, brassinosteroid, salicylic acid, jasmonic acid and ethylene) being influenced by drought stress. Conclusion: The overall result of comparative transcriptomic investigation suggests that indigenous aromatic rice cultivars Badshabhog and Jamainadu explored varying strategies to deal with post-imbibitional dehydration stress. The cultivar Badshabhog exhibited a significantly greater molecular reprogramming presumably more through up-regulation of metabolic and energy demanding processes along with implementing better signaling strategies, antioxidative defense mechanism, DNA repair and transcriptional regulation vis-a-vis the cultivar Jamainadu.
Association of Gut Microbiome and Vitamin D in Knee Osteoarthritis Patients
Authors: Ramasamy Boopalan , Magne Fabien , Tripathy Sujit Kumar , Venugopal Giriprasad , Mukherjee Diptasree , Balamurugan Ramadass
Published: January 2021

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.
Premature Neonatal Gut Microbial Community Patterns Supporting An Epithelial TLR-Mediated Pathway For Necrotizing Enterocolitis
Authors: Shaw Alexander G , Sim Kathleen , Rose Graham , Wooldridge David J. , Li Ming-Shi , Misra Raju V. , Gharbia Saheer , Kroll J. Simon
Published: January 2021

Background: Necrotising enterocolitis (NEC) is a devastating bowel disease, primarily affecting premature infants, with a poorly understood aetiology. Prior studies have found associations in different cases with an overabundance of particular elements of the faecal microbiota (in particular Enterobacteriaceae or Clostridium perfringens), but there has been no explanation for the different results found in different cohorts. Immunological studies have indicated that stimulation of the TLR4 receptor is involved in development of NEC, with TLR4 signalling being antagonised by the activated TLR9 receptor. We speculated that differential stimulation of these two components of the signalling pathway by different microbiota might explain the dichotomous findings of microbiota-centered NEC studies. Here we used shotgun metagenomic sequencing and qPCR to characterise the faecal microbiota community of infants prior to NEC onset and in a set of matched controls. Logistic regression was used to segregate cases from control samples using both microbial and clinical data.Results: We found that the infants suffering from NEC fell into two groups based on their microbiota; one with relatively low levels of CpG DNA in bacterial genomes and the other with high abundances of organisms expressing LPS. The identification of these characteristic communities was reproduced using an external metagenomic validation dataset. We suggest that these two patterns represent the stimulation of a common pathway at extremes; the LPS leading to overstimulation of TLR4, whilst low levels of CpG fail to sufficiently stimulate TLR9. Conclusions: The identified microbial community patterns support the concept of NEC resulting from TLR-mediated pathways. Identification of these signals suggests characteristics of the gastrointestinal microbial community to be avoided to prevent NEC. Potential pre- or pro-biotic treatments may be designed to optimise TLR signalling.
Posttraumatic Subperiosteal Orbital Hematoma With Intracranial Hemorrhage in A Male Infant
Authors: Lee Yeon Jeong , Yoo Yungju
Published: January 2021

Background: To the best of our knowledge, there has been no report of subperiosteal orbital hematoma combined with intracerebral hemorrhage in pediatric patients.Case presentation: A healthy 9-month-old boy with left superior tarsal conjunctival prolapse was admitted to the emergency room after left periorbital blunt trauma. Computer tomography of the brain showed a left orbital roof fracture and subperiosteal orbital hematoma with acute intracerebral hemorrhage. He received emergency craniotomy. Three days after the craniotomy, the subperiosteal hematoma and proptosis increased. An anterior orbitotomy with orbital subperiosteal hematoma evacuation and drain placement were performed. Nine months after surgery, the left blepharoptosis and conjunctival prolapse improved and fix and follow were good in his both eyes. However, a new-onset intermittent exotropia and left hypotropia were detected. Conclusions: Orbital subperiosteal hematoma must be considered in the differential diagnosis of acute unilateral proptosis after trauma. In infants and children, a thorough work-up to detect concomitant intracerebral hemorrhage is necessary. Prompt surgical removal of hematoma is recommended to prevent complications
External Beam Partial Breast Irradiation Versus Whole Breast Irradiation for in Early Breast Cancer：A Systematic Review and Meta-Analysis
Authors: Dai Peiling , Chen Kai , Li Lan , Wang Li , Xia Yaoxiong , Hou Yu , Zhang Lan , Chang Li , Li wenhui
Published: January 2021

PurposePostoperative radiotherapy can reduce the recurrence of breast cancer. Postoperative radiotherapy is divided into whole breast irradiation (WBI) and partial breast irradiation (PBI) for early breast cancers. Due to the characters of saving time, money, and easy to deliver, external beams PBI (EB PBI) is brought into focus. However, the researches on outcomes, safety, and efficacy between EB PBI and WBI are still insufficient. We concluded a meta-analysis for LRR, regional node recurrence, contralateral breast cancer, distant recurrence, mortality, less acute skin toxicity (˃ 1 grade), late skin toxicity and the cosmetic score of external beam partial breast irradiation (EB PBI) and whole breast irradiation(WBI) to develop a radiotherapy plan for early low recurrence risk breast cancer patients. MethodWe searched Pubmed、Embase、Cochrane Library、Clinicaltrals. Study eligibility criteria are as below: (1) RCTs for EB PBI vs WBI; (2) Histologically confirmed breast cancer; (3) AJCC staged Tis-2N0-1M0; (4) ≥ 40 years old; (5) Tumor size ≤ 3 cm;(6) microscopically clear margins ≤ 5 cm; (7) Mean follow-up time༞5 years. All data is used by Cochrane’s Review Manager 5.3 (RevMan) to process.ResultsThere were 4 RCT studies included in our study with 1999 patients in EB PBI group and 1999 patients in EB PBI. There was no statistic difference between PBI and WBI groups in local recurrence rates (RR = 1.15; 95% CI, 0.76 to 1.74; p = 0.52; I2 = 0%), regional node recurrence(RR = 1.00; 95% CI, 0.49 to 2.04, p = 0.99, I2 = 0%), contralateral breast cancer (RR = 0.79; 95% CI, 0.54 to 1.16; p = 0.23; I2 = 0%), distant recurrence(RR = 1.00; 95% CI, 0.63 to 1.59; p = 1.00; I2 = 0%), non-breast second cancer (RR = 1.03; 95% CI, 0.50 to 2.16; p = 0.93; I2 = 83%), mortality(RR = 0.96; 95% CI, 0.60 to 1.55; p = 0.88, I2 = 54%). EB PBI had worse cosmetic score (RR = 1.56; 95% CI, 1.04 to 2.34; p = 0.003, I2 = 84%), less acute skin toxicity (˃ 1 grade) (RR = 0.17; 95% CI, 0.07 to 0.42; p༜ 0.0001, I2 = 87%) and late skin toxicity(RR = 0.65; 95% CI, 0.48 to 0.88; p = 0.005; I2 = 27%) than WBI.ConclusionEB PBI has similar LRR, regional node recurrence, contralateral breast cancer, distant recurrence, non-breast second cancer and mortality with WBI. But EB PBI has worse cosmetic score, less acute skin toxicity (˃ 1 grade) and late skin toxicity than WBI.
The Lecture is Not Dead: Combined Peer Assisted Flipped Class, an Alternative to Classical Lecture in Basic Medical Education
Authors: Shawky Noha Osama , EL-Bab Mohamed Fath , Waly Nermien
Published: January 2021

Student engagement at lectures is declining especially for basic sciences. Lecture is main method of physiology teaching. It has been increasingly challenging to employ new educational methodologies in teaching physiology for several economical and technical reasons. Our objective was to enhance lecture attendance and increasing student engagement in physiology lectures. Combined peer assisted learning (PAL) and flipped classroom (FC) strategies (PAFC) was employed in the teaching of neurophysiology course for second year medical students. Course Material and reading assignments were provided ahead of class on instructor and departmental websites. Twenty Students participated in lectures preparation and presentation under instructor’s supervision. Class members participation was conducted via pre-class reading assignments, in class discussions and instructor guided questions. Method evaluation was conducted using both course surveys, quizzes, end of course evaluations and lecture attendance. lecture attendance showed about 30 % increase compared to anatomy class conducted in classical lecture format. Course surveys revealed a 77% of students were satisfied with the new methodology while 23% preferred the traditional method. All PAFC participants expressed their positive feedback when interviewed after the course had ended and their comments was documented. End of course evaluations showed that class results were Comparable to anatomy course taught in traditional method (same class and conducted at the same time). In conclusion, PAFC can be beneficial in teaching basic science courses for medical students. It can enhance lecture attendance and student satisfaction. Also, it can provide an affordable alternative method to improve medical education in institutes with limited resources.
Effect of Dynamic Stiffness of Fasteners on Vibration and Acoustic Radiation of a Ballastless Track
Authors: xu hanwen , han jian , xiao xinbiao , liu xiaolong , liu moukai , jin xuesong
Published: January 2021

A new model for a single wheel rolling over a metro ballastless track is developed. It is used to carry out the analysis on the effect of dynamic characteristics of fastener on the vibration and noise radiation of the wheel and the track in the vertical direction, under the excitation of the wheel/rail uneven surfaces in detail. In this analysis, a rail is modeled as a Timoshenko beam resting on discrete rubber booted short sleepers, and the sleepers are connected with the slab through linear springs and damping units, the slab is modeled by using the FE method, the fastener is characterized by using the Poynting-Thomson model which takes into account that the stiffness and dumping of the fasteners vary with vibration frequency in their service. The dynamic characteristics of the fastener include the variation of its stiffness and damping with frequency. The analysis considers that the fastener dynamic stiffness increases with the excitation frequency while its damping decreases. The vibration and acoustic radiation of the wheel/track is, to varying degree, affected by the dynamic property of the fastener. The vibration and acoustic radiation of the sleeper and the slab is greatly affected by the dynamic property of the fastener. But the effect of the total noise level of the wheel and the track by the dynamic property of the fastener is not so large because the wheel and rail noise is dominant in the whole analyzed system. These conclusions have certain reference values for the study of the vibration and noise reduction measures of the wheel and track coupled system using the fastening characteristic.
CT measurements of optic nerve sheath diameter to evaluate the outcome of acute carbon monoxide poisoning
Authors: han Jiayan , Zhuo Luo , Chen Dongmei , Sun Yan , Li Fan , Huang Shouqiu , Chen Xiaobing , Wang Yanli , Li Xiaomin
Published: January 2021

Background

Thousands of people die each year from carbon monoxide poisoning. There are no clear indicators for evaluating the outcome of carbon monoxide poisoning. We aimed to evaluate the relationship between optic nerve sheath diameter (ONSD) and ONSD/ transverse eyeball diameter ((ETD)) measured by CT and the outcome of acute carbon monoxide poisoning.
Methods

We retrospectively analyzed all acute carbon monoxide poisoning patients who had received CT November 2017 to July 2020. All patients underwent cranial CT examination on the day of admission, the ONSD at 3 mm behind the eyeball on CT was measured and the ONSD/ETD ratio was calculated by ETD. According to the CPC score, the patients were divided into two groups: good outcome group and poor outcome group. ROC curve was used to evaluate the diagnostic value of each index in outcome. Logistic regression analysis was used to screen the related factors affecting the outcome of patients.
Results

We identified 146 patients who received cranial CT as the first clinical evaluation after acute carbon monoxide poisoning, which including 108 patients with good outcome and 38 patients with poor outcome. Compared with the good outcome group, there were significant differences in ONSD, ONSO/ETD, Lactic acid, CPK, NSE, PSS and APACHEII scores between the poor outcome group and the poor outcome group. An ONSD model for predicting poor outcome was established, and the corresponding ROC curve was drawn. The area under the ROC curve (AUC) was 0.925, the best prediction probability out-off value was 0.3585, the sensitivity was 89.5%, and the specificity was 94.4%. The same method obtains the prediction model of ONSD/ETD, the AUC is 0.916, the out-off value of the best prediction probability is 0.3547, the sensitivity is 89.5%, and the specificity is 92.6%.
Conclusion

ONSD and ONSD/ETD are significantly related to the outcome of patients with acute carbon monoxide poisoning. The outcome is poor when ONSD > 5.68 mm or ONSD/ETD > 0.24. Measuring the diameter of optic nerve sheath by CT may be a simple and rapid method to evaluate the clinical outcome of patients with carbon monoxide poisoning.
The Potential for Arrhythmia during Central Venous Catheter Insertion- to where does the guidewire migrate?
Authors: Reichmann Daphna , Sadeh Re'em , Galante Ori , Almog Yaniv , Novack Victor , Fuchs Lior
Published: January 2021

BackgroundCentral Venous Catheters (CVC) are being used in both intensive care units and general wards for multiple purposes. A previous study1 observed that during CVC insertion through Subclavian Vein (SCV) or the Internal Jugular Vein (IJV) the guidewire is sometimes advanced to the Inferior Vena Cava (IVC), and at other times to the right atrium. The rate of IVC wire cannulation and the association with side and point of insertion is unknown.ObjectiveIn this study, we describe guidewire migration location during real time CVC cannulation (right atrium versus IVC) and report the association between the insertion site and side of the CVC and the location of guidewire migration, Right Atrium (RA)/Right Ventricle (RV) versus IVC guidewire migration.DesignThis is a retrospective study of the prospectively and systematically collected data on CVC insertion under real time trans thoracic ultrasound.SettingThe medical Intensive Care Unit in Soroka Medical Center, among patients that have received CVC during the study years 2014–2020.Main outcome measures:The rate of IVC versus right atrium/right ventricle wire migration during the procedure were analyzed. The association between the side and point of CVC insertion and the wire migration site was analyzed as well.ResultsOne hundred and sixty-six patients were enrolled. 33.7% of wires migrated to the IVC and 66.3% to the versus right atrium/right ventricle. The rate of wire migration to the IVC was similar in the IJV site and the SCV site. There was no association between the side of CVC insertion and wire migration to the IVC.ConclusionAbout a third of all wire migrations, during CVC Seldinger technique insertion, were identified in the IVC, with no potential for wire associated arrhythmia. There was no association between CVC insertion point (SCV versus IJV) nor the side of insertion and the site of guidewire migration.
Abrogation of group III phospholipase A2 inhibits tumor growth and metastasis in ovarian cancer and promotes chemo-sensitization
Authors: Ray Upasana , Roy Debarshi , Jin Ling , Thirusangu Prabhu , Staub Julie , Xiao Yinan , Kalogera Eleftheria , Hendrickson Andrea E. Wahner , Cullen Grace , Goergen Krista , Oberg Ann L. , Shridhar Viji
Published: January 2021

Background

Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined.
Methods

CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis.
Results

Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited oncogenesis. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy.
Conclusions

Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.
Gut Microbiome Analysis As A Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma
Authors: Li Jialiang , Li Xueyan , Zhang Sina , Jin Chen , Lin Zixia , Xie Xiaozai , Deng Liming , Wang Mingxun , Ma Jun , Ding Xiwei , Liu Yaming , Wang Yi , Chen Gang
Published: January 2021

BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.
SUMOylation of S100A10 promotes its nuclear localization and enhances the migration and invasion of PGCCs and their daughter cells
Authors: Zhao Qi , Zhang Kexin , Li Zugui , Zhang Hao , Fu Fangmei , Zheng Minying , Zhang Shiwu
Published: January 2021

Background

Our previous studies have confirmed that cobalt chloride (CoCl2) or chemoradiotherapy could induce the formation of polyploid tumor giant cells (PGCCs) and daughter cells derived from PGCCs had strong proliferation and migration abilities. However, the detailed molecular mechanism is unclear.
Methods

Cell functional experiments, co-immunoprecipitation, MG132 and ginkgolic acid treatment, western blot, and ChiP-Seq were used to identify the mechanism of S100A10 nuclear location.
Results

CoCl2 was used to induce the formation of PGCCs in LoVo and HCT116 CRC cells. The proliferation and migration abilities of PGCCs and their daughter cells decreased significantly after S100A10 knockdown. In the control cells, S100A10 was mainly ubiquitinated, while in PGCCs and daughter cells, S100A10 was mainly SUMOylated, which was associated with S100A10 nuclear location. After SUMO1 was inhibited, the nuclear S100A10 in PGCCs and daughter cells decreased, and their proliferation and migration abilities significantly decreased. ChiP-Seq combined with real-time fluorescent quantitative PCR showed that S100A10 regulated the expression of neutrophil defensin 3 (DEFA3), receptor-type tyrosine-protein phosphatase N2 (PTPRN2), and rho guanine nucleotide exchange factor 18 (ARHGEF18). The expression of S100A10 in the nuclei and cytoplasm of rectal cancer after neoadjuvant chemoradiation (nCRT) and liver metastases increased compared with that in rectal cancer without nCRT.
Conclusion

The expression and nuclear localization of S100A10 modified by SUMOylation were associated with the high proliferation and migration of PGCCs and their daughter cells, and the differentiation, metastases, and relapse of CRCs by regulating the expression of ARHGEF18, PTPRN2, and DEFA3.
β-Elemene Inhibits Proliferation of Non-Small-Cell Lung Cancer by Targeting ALDH3A1 to Regulate Metabolic Reprogramming
Authors: Chen Yang , Li Xuena , Che Xiaofang , Yang Yi , Diao Yao , Deng Mingming , Hou Kezuo , Qu Xiujuan , Liu Yunpeng , Li Yaming , Zhang Ye , Hu Xuejun
Published: January 2021

Background

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in the world. Although the improvement of treatment has significantly prolonged the survival of NSCLC patients, most patients still face recurrence because of drug resistance. Therefore, it is urgent to find more effective drugs to improve the NSCLC treatment and survival rate of patients.
Methods

Network pharmacology tools were comprehensive applied to analyze β-elemene and the anticancer effects of β-elemene were evaluated both in vitro and in vivo. What’s more, the underlying mechanisms were investigated via metabolomics analysis, 18FDG-micro-PET scan and molecular biology experiment.
Results

β-elemene exhibited potent inhibitory effects on NSCLC cells proliferation by alternating the cell cycle without significantly apoptosis in NSCLC cells. Mechanistically, we found that β-elemene regulating metabolic reprogramming of NSCLC via targeting Aldehyde Dehydrogenase 3 Family Member A1 (ALDH3A1). Subsequently, the metabolic reprogramming of NSCLC cells regulated by β-elemene lead to increased hydroxylation of α-ketoglutarate (α-KG), and degraded Hypoxia Inducible Factor1 Subunit Alpha (HIF1α), which cause accelerated reduction of aerobic glycolysis in NSCLC in vivo and vitro through facilitating HIF1α/LDHA pathway. Moreover, the reduction of aerobic glycolysis effect of β-elemene in vivo was confirmed by the reduced SUV values and the decreased expression of Ki-67 and HIF1α/LDHA pathway proteins in tumor tissues from xenograft mouse models.
Conclusion

β-Elemene exhibits strong metabolic reprogramming effects, glycolysis was suppressed while OXPHOS was increased in NSCLC cells via targeting ALDH3A1 and HIF1α/LDHA pathway, which provides a new theoretical basis for the clinical treatment of patients with NSCLC.
Novel full-human CD22-CAR therapy overcomes resistance to previous CD19/22-CAR regimens in ALL
Authors: Tan Yue , Cai Haodong , Li Chuo , Deng Biping , Song Weiliang , Ling Zhuojun , Yang Yongkun , Niu Panpan , Meng Guangrong , Cheng Wei , Xu Jinlong , Duan Jiajia , Wang Zelin , Yu Xinjian , Feng Xiaoming , Zhou Jianfeng , Pan Jing
Published: January 2021

BackgroundCD19- and/or CD22-targeted chimeric antigen receptor (CAR) T cells efficiently induced remission in patients with B acute lymphoblastic leukemia (B-ALL), but a considerable proportion of patients relapsed after both CD19- and CD22-CAR therapies associated with the loss or downregulation of target antigen. Re-infusions of the prior used CAR T cells were usually ineffective. In contrast to the frequent loss of CD19, low level of CD22 is usually present on leukemia cells post CAR therapy, suggesting that newly designed CD22-CAR therapies may be effective in these patients.MethodsA yeast full-human single-chain variable fragment (scFv) library and a high-throughput NFAT reporter assay were utilized to screen several full-human CD22-CAR candidates; CD107 assay and in vitro cytotoxicity assay was used to evaluate the effector function of CAR T cells; membrane proteome assay was conducted to determine the specificity of the CAR toward the target antigen; a leukemia animal models was used to test the in vivo efficacy of CAR T cells. A phase I trial (ChiCTR2000028793) was conducted to assess the safety and effectiveness of CD22-CARFH80 therapy in 8 children with B-ALL resistant to or relapsed after prior CD19- and CD22-CAR treatment.ResultsWe identified a full-human CD22-CAR construct termed CD22CARFH80 which could mediate superior anti-leukemia activity in vitro and in a leukemia animal model and had good specificity to the target antigen. Data from the trial showed that with CD22-CARFH80 T-cell therapy, 6/8 (75%) patients including 2 who had CD22low blasts achieved complete remission; 1 patient had a partial response. CAR T cells efficiently expanded in vivo, while the toxic effect is low in most patients. At a median follow-up of 5 months, 4/6 (57%) patients remained in remission.ConclusionsTherapy with a newly invented CD22-CARFH80 overcomes the resistance to prior versions of CD19- and CD22-CAR formats and elicits potent anti-leukemia responses with an acceptable safety profile, representing a promising salvage regimen for B-ALL that fails in prior CD19- and CD22-CAR treatments.Trial registrationClinicalTrials.gov: ChiCTR2000028793; registered 4 January, 2020. http://www.chictr.org.cn/showproj.aspx?proj=47857
Cerebral Ventriculomegaly in Myotonic Dystrophy Type 1: Normal Pressure Hydrocephalus-like Appearances on Magnetic Resonance Imaging
Authors: Iida Saya , Seino Hiroko , Nagahata Fumiko , Tatsuo Soichiro , Maruyama Sho , Kon Seiko , Takada Hiroto , Matsuzaka Masashi , Sugimoto Koichiro , Kakeda Shingo
Published: January 2021

Background: Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI.Methods: One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used multivariate logistic regression analyses.Results: The z-Evans Index was significantly larger in the patients than in the controls (0.30±0.05 vs. 0.24 ± 0.02; p < 0.01). The multivariate logistic regression analyses showed that the z-Evans Index was independently associated with the patient age (p <0.05), CA (p < 0.01), Sylvian fissure dilation (p < 0.01), and pathological brain atrophy (p < 0.01) but not with CTG repeat numbers, CS-EPVS, or temporo-polar WML. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH.Conclusions: Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.
Transcriptome Analysis of a Jujube (Ziziphus Jujuba Mill.) Cultivar Response to Heat Stress
Authors: Yang Lei , Jin Juan , Fan Ding-yu , Hao Qing , Niu Jianxin
Published: January 2021

Background: Heat stress (HS) is a common stress and influences the growth and reproduction of plant species. We found and bred a putative heat-resistant jujube (Ziziphus jujuba Mill.) cultivar (JHR17) in previous study. Results: In the current study, we made the seedlings of ‘JHR17’ cultivar to be under HS (45°C) for 0, 1, 3, 5 and 7 days, respectively, and the leaf samples (HR0, HR1, HR3, HR5 and HR7) were collected accordingly. Fifteen cDNA libraries from ‘JHR17’ leaves were built with a transcriptome assay. The RNA sequencing (RNA-seq) and transcriptome comparisons were performed, and the results indicated that 1642, 4080, 5160 and 2119 differentially expressed genes (DEGs) were identified in HR1 vs. HR0, HR3 vs. HR0, HR5 vs. HR0 and HR7 vs. HR0, respectively. Gene Ontology (GO) analyses of the DEGs from these comparisons were implemented. Conclusion: It revealed that a series of biological processes, involved in stress response, photosynthesis and metabolism, were enriched successfully, suggesting that lowering or up-regulating these genes of processes might play important roles in response to HS. This study may contribute to understand the molecular mechanism of ‘JHR17’ cultivar response to HS, and be beneficial for developing jujube cultivars to improve heat resistance.
Amended Informative Negative Whole Exome Sequencing Results
Authors: Alsubaie Lamia , Aloraini Taghrid , Alfarsi Anar , Mutairi Fuad Al , Alswaid Abdulrahman , Alothaim Ali , Eyaid Wafaa , Albalwi Mohammed , Asinan Aqila , Alniwaider Rashed , Muitiri Abdulrahman Al , Alfadhel Majid , Alfares Ahmed
Published: January 2021

Background: Whole exome sequencing (WES) is widely used as a first-tier diagnostic test. The diagnostic yield for WES is estimated at approximately 50%, leaving the requesting clinician with 50% ambiguous or negative results in cases where the diseases-causing variants could not be identified. Methods: We retrospectively assessed the results of all WES tests requested from 2015 to 2018 at our institution. We included participants with a negative test result, irrespective of the phenotype. Complete data collection, medical-record extraction, and additional analysis were done for qualifying cases. Results: The cohort included 151 participants with a negative WES result. Of the sample, 18% (n=27) were discharged from the genetic clinic, and only three cases required additional genetic testing prior to discharge. The decision to discharge a patient was based on several factors, including a mild phenotype (i.e. a phenotype that can be resolved and doesn’t require surgical, rehabilitation or medical intervention), a confirmed multifactorial condition, or the patient is developing according to the milestones for his age group and has a negative family history. The discharge rate and the period of being followed at the clinic improved over time. In 2015, none was discharged, and in 2016, nearly 100% of the negative cases were discharged in 6-12 months. In 2017, 65% of the cases were discharged in less than six months, and all cases tested in 2018, were discharged from the clinic in less than three months.Conclusion: Informative negative WES results lower the cost of additional testing, reduce the number of follow-up consultations, and result in the reassurance or discharge the patient. The informative negative WES results (18%) can be combined with the hit rate of the WES (50%) in consanguineous population, increasing the clinical utility of WES testing to 68%.
Maintaining Plasmodium Falciparum Gametocyte Infectivity During Blood Collection and Transport for Mosquito Feeding Assays in the Field
Authors: Soumare Harouna M. , Guelbeogo Wamdaogo Moussa , Vegte-Bolmer Marga van-de , Gemert Geert-Jan van , Soumanaba Zongo Soumanaba , Ouedraogo Alphonse , Ouattara Maurice S. , Abdullahi Ahmad , Jadama Lamin , Camara Muhammed M. , Gaye Pa Modou , Mendy Michael , Davis Nwakanma , Tiono Alfred B. , D’Alessandro Umberto , Drakeley Chris , Bousema Teun , Moreno Marta , Collins Katharine
Published: January 2021

BackgroundMosquito feeding assays using venous blood are commonly used for evaluating the transmission potential of malaria infected individuals. To improve the accuracy of these assays, care must be taken to prevent premature activation or inactivation of gametocytes before they are fed to mosquitoes. This can be challenging in the field where infected individuals and insectary facilities are sometimes very far apart. In this study, a simple, reliable, field applicable method is presented for storage and transport of gametocyte infected blood using a thermos flask. MethodsThe optimal storage conditions for maintaining the transmissibility of gametocytes were determined initially using cultured Plasmodium falciparum gametocytes in standard membrane feeding assays (SMFAs). The impact of both the internal thermos water temperature (35.5 – 37.8°C), and the external environmental temperature (room temp – 42°C) during long-term (4hr) storage, and the impact of short-term temperature changes (room temp – 40°C) during membrane feeding assays was assessed. The optimal conditions were then evaluated in direct membrane feeding assays (DMFAs) in Burkina Faso and The Gambia where blood from naturally infected gametocyte carriers was offered to mosquitoes immediately and after storage in thermos flasks. ResultsUsing cultured gametocytes in SMFAs it was determined that an internal thermos water temperature of 35.5°C and storage of the thermos flask between RT (~21.3°C) and 32°C was optimal for maintaining transmissibility of gametocytes for 4 hours. Short-term storage of the gametocyte infected blood at temperatures up to 38°C (range: RT, 30°C and 38°C) did not have a negative effect on gametocyte infectivity. Using samples from natural gametocyte carriers (47 from Burkina Faso and 16 from The Gambia), the prevalence of infected mosquitoes and the intensity of oocyst infection was maintained when gametocyte infected blood was stored in a thermos flask in water at 35.5°C for up to 4 hours.ConclusionsThis study determines the optimal long-term (4 hours) storage temperature for gametocyte infected blood and the external environment temperature range within which gametocyte infectivity is unaffected. This will improve the accuracy, reproducibility, and utility of DMFAs in the field, and permit reliable comparative assessments of malaria transmission epidemiology in different settings.
Predictors of Physical and Mental Health in Healthcare Teams Working With COVID-19 Patients: A Scoping Review Protocol.
Authors: Aguirre-Duarte Nelson Alberto , Ovretveit John , Kenealy Timothy
Published: January 2021

IntroductionAs a result of the current pandemic (COVID-19), many clinical teams are exposed to stressful situations that may lead to physical and mental issues for clinical staff themselves (we exclude the effects of personal infection with the virus). Recent studies suggest some predictors could depend on context, notably country and the type of the health system. Methods and AnalysisThis protocol was follows using the PRISMA-ScR guideline (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), which was revised and approved by the research team. This study aims to identify factors and evidence of the physical, behavioural and mental consequences of sustained clinical practice in a continuing pandemic. Our research seeks to fill this gap in the literature, and the results may suggest to governments, healthcare authorities and healthcare providers appropriate measures to mitigate risks to healthcare workers during a pandemic response.Dissemination and ethicsThe current research design is based on the use of publicly available information and does not require ethical approval. The findings will be disseminated in conferences. Results will be published and additionally shared with relevant local and national authorities.
Effects of Chicken Farming on Soil Phosphorus Availability and Associated Microbial Properties in Lei Bamboo (Phyllostachys praecox) Forest Ecosystems
Authors: Gai Xu , Li Shaocui , Zhang Xiaoping , Bian Fangyuan , Yang Chuanbao , Zhong Zheke
Published: January 2021

Background: Bamboo-chicken farming (BCF) is a popular bamboo complex management model in Southeast Asia owing to its high economic benefits. However, the effects of BCF on phosphorus (P) availability and the associated microbial communities in soil remain poorly understood. In this study, we compared the soil properties, P fractions, phosphatase activities, and bacterial community compositions in the surface soil (0–20 cm) of a typical bamboo (Phyllostachys praecox)-chicken farming system under different grazing densities (represented as distances of 5, 15, 25, and 35 m from the henhouse, respectively). The variables were also compared with the soil measurements from an adjacent pure bamboo forest without chicken framing (control site).Results: We observed a significant increase in soil pH, cation exchange capacity (CEC), total N (TN), total P (TP), and available potassium (AK) with increasing grazing density, while soil organic carbon (SOC) showed no significant difference between the sites. The total P accumulation of the soil was also more rapid than that of SOC and TN with increasing grazing density. Labile P and moderately labile P dominated the soil P accumulation under BCF. In particular, Resin-Pi (labile P), NaHCO3-Pi (labile P), and 1 M HCl-Pi (moderately labile P) increased by 100–233%, 83–183% and 414–1314%, respectively, compared with the control values. In contrast, the contribution of labile or moderately labile organic phosphorus to the total phosphorus (Pt) content decreased significantly with increasing grazing density from 38.54% (control) to 17.65% (5-m site). Phosphatase activity also increased with increasing grazing density, which suggests that BCF effectively promoted the mineralization of soil Po. A redundancy analysis showed that the changes in bacterial community structure were closely related to Resin-Pi and 1 M HCl-Pi (r2 = 0.938 and 0.958, respectively). The relative abundances of the phosphobacteria Flavobacterium, Pseudomonas, Streptomyces, and Arthobacter increased with increasing grazing density, while the abundance of Burkholderia decreased at the 5-m site. Inorganic P (Resin-Pi, NaHCO3-Pi, and 1 M HCl-Pi) was positively correlated with the abundances of Flavobacterium, Pseudomonas, and Arthrobacter but negatively correlated with the abundance of Burkholderia; this highlights the different functional bacteria involved in P cycling. Conclusions: We conclude that BCF generally increases soil P availability and supply, and the changes in the P forms were closely related to the changes in soil bacterial community composition. However, excessive grazing density or long-term BCF practices can cause soil nutrient imbalance, labile and moderately labile P accumulation, and P leaching. Therefore, appropriate grazing densities and/or an interval of no grazing are required under the BCF model for effective and sustainable bamboo forest management.
Surgical Resection Significantly Promotes the Overall Survival of Patients with Hepatocellular Carcinoma: A Propensity Score Matching Analysis
Authors: Hsieh Pei-Min , Lin Hung-Yu , Hung Chao-Ming , Lo Gin-Ho , Lu I-Cheng , Lee Chih-Yuan , Wu Tsung-Chin , Yeh Jen-Hao , Hsiao Pojen , Li Yu-Chan , Wang Ya-Chin , Hsieh Kun-Chou , Chen Yaw-Sen , Lin Chih-Wen
Published: January 2021

Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.