bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Prognostic Biomarkers of Potential Hub Genes in Urothelial Carcinoma and Function in Microenvironment
Authors: Chu Wei , Zhang Bing , Gong Haifeng , Zhao Qianqian , Chen Jun , Ji Hong
Published: August 2021

Background: Urothelial carcinoma (UC) is the most common histological type of urinary system. In the past decades, despite the advances in UC diagnosis and therapy, there are still challenges to improve the overall survival (OS) of UC patients. PD-L1 inhibitor and PD-1 inhibitor have been approved for treating invasive UC, however, only about 20% of patients with metastatic UC show clinical benefits from immune checkpoint inhibitors. Therefor, bioinformatics tools were utilized to screen prognostic-related biomarkers, and analyze their relationship with immunocyte in UC, hoping to provide new ideas for the clinical treatment of UC patients.Results: In total, 63 DEGs were identified from the GEO database of UC, of which 31 and 32 were up-and down-regulated. GO/KEGG pathway analysis identified DEGs were mainly enriched in the collagen catabolic process, extracellular matrix (ECM) organization, ECM structural constituent and ECM-receptor interaction. Nine hub genes (i.e. COL1A1, COL1A2, COL3A1, COL5A2, MMP9, POSTN, SPP1, VCAN and THBS2) upregulated in invasive UC compared with superficial UC were identified. cBioportal database analysis showed that 35% of UC patients presented genetic variants in the hub genes, of which amplification and deletion mutations were the most common. ONCOMINE and UALCAN database analysis showed that the mRNA expression of all hub genes in invasive UC was significantly higher than that in superficial UC and normal tissues. HPA database analysis showed that there was up-regulation of COL3A1, SPP1, POSTN and VCAN protein in UC tissues than in normal tissues. GEPIA showed that COL1A2, COL3A1, THBS2, and VCAN were positively correlated with the OS rate among patients with UC (P < 0.05). UALCAN showed that UC patients with high expression of COL1A1, COL1A2, COL5A2 and POSTN had a poorer prognosis (P < 0.05). TRRUST database analysis indicated that there was a significant correlation between the expression of the hub genes and the infiltration of CD4+T cells, CD8+T cells, macrophages, neutrophils and dendritic cells. Conclusion: Hub genes played important roles in pathogenesis and treatment prognosis of UC and they can provides new biomolecular predictions for immunotherapy and prognosis judgment of UC.
Maximum incisal opening, caries experience and health-related quality of life in patients undergoing treatment for head and neck cancer – A longitudinal cohort study.
Authors: Dholam Kanchan P , Somani Priyanka , Dugad Jinesh , Kharade Pankaj , Rane Pallavi P , Agarwal Jai P , Singh Gurkaran Preet
Published: August 2021

Purpose
Prospective evaluation of the change in maximum incisal opening (MIO) in patients receiving treatment for head neck cancer (HNC), and its interaction with clinical parameters such as tumor site/ sub-site and type of treatment received. Secondary aim was to ascertain the longitudinal change in dental caries experience and health-related quality of life (HRQoL) during the study period.
Methods
Seventy treatment-naïve patients undergoing treatment for squamous cell carcinoma (SCC) of oral cavity and/or oropharynx were assessed at 3 designated time-points; pre-treatment (T0), immediate post-treatment (T1) and 6-months post-treatment (T2). The primary study variable was change in MIO (cm) across 3 time points (T0, T1, T2). Dental caries incidence was measured using decayed, missing, filled teeth (DMFT) index and HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and H&N-35). Change in DMFT and HRQoL was assessed between T0 and T2. Non-parametric repeated measures ANOVA was used to analyse the longitudinal change in MIO and DMFT scores and their interaction with clinical parameters respectively. Wilcoxon signed-rank test was used to compare corresponding HRQoL domains between T0 and T2. All statistical tests were 2-sided, and differences with a p-value < 0.05 were considered statistically significant.
Results
Sixty-seven eligible HNC patients showed a significant change in mouth-opening and dental caries experience from T0 to T2, irrespective of tumor site/ sub-site and type of treatment (p < 0.001). Site-wise, patients with oral cavity cancer and specifically maxillary tumors; treatment-wise those undergoing surgery and/or, multi-modal treatment showed persistently reduced mouth opening late post-treatment. There was a statistical increase in head-and-neck site specific HRQoL symptoms at T2. A high prevalence (69%) of post-treatment trismus was noted especially in patients undergoing multi-modality treatment (83%).
Conclusion
Patients undergoing treatment for HNC demonstrate a significant longitudinal change in mouth-opening and caries incidence. They may show partial recovery of MIO at 6-months after an initial decrease in the immediate post-treatment period.
Effects of Intermittent Bolus Paravertebral Block On Analgesia and Recovery in Open Hepatectomy: A Retrospective, Cohort Study.
Authors: Wang Jin , Cui Xulei , Zhang Yuelun , Zhang Zhiyong , Mao Yilei , Sang Xinting , Huang Yuguang
Published: August 2021

Background

Experiences of paravertebral block use in hepatectomy were limited. We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in hepatectomy.
Methods

We selected patients receiving two types of analgesia programs, with matched age, sex and body mass index from a prospective perioperative analgesia and nerve block database: (1) PVB: intermittent bolus paravertebral block (0.5% ropivacaine 25ml before surgery plus 0.125ml•kg− 1 0.2% ropivacaine bolus per hour after surgery) and self-controlled intravenous bolus morphine pump till postoperative 48 hours; (2) control: self-controlled intravenous bolus morphine pump till postoperative 48 hours. The baseline, operation, and postoperative analgsia and recovery data were compared between groups.
Results

Thirty-eight patients in each group were included in the analysis. Intraoperatively, PVB group used less sevoflurane (difference − 0.1 (-0.2, 0.0) %, P = 0.019), and more ephedrine (U = 986, P = 0.004) and crystalloid (U = 936, P = 0.024) than control group. The mean arterial pressure in PVB group was lower than that in control group (difference − 4mmHg, 95%CI -8 ~ 0mmHg, P = 0.031) but similar to its baseline level (difference 2, 95%CI -1 ~ 5, P = 0.153). Postoperatively, PVB group had lower cumulative morphine consumption at postoperative 2 (U = 371.5, P < 0.001), 4 (U = 349.5, P < 0.001), 12 (U = 342.0, P < 0.001), 24 (U = 338.5, P < 0.001) and 48 (U = 392.5, P = 0.001) hour, lower pain numerical rating scale score at rest at postoperative 0 (U = 299.5, P < 0.001), 2 (U = 355.5, P < 0.001) and 4 (U = 332.0, P < 0.001) hour, and on movement at postoperative 0 (U = 269.5, P < 0.001), 2 (U = 405.0, P = 0.001), 4 (U = 382.5, P < 0.001) and 12 (U = 1179.5, P = 0.003) hour than control group. PVB group also had lower rescue analgesia rates (OR 0.29, 95%CI 0.08 ~ 1.00, P = 0.044), higher emergence satisfaction (5 (4, 5) vs 4 (4, 5), P = 0.018) and lower drowsiness score (0 (0,1) vs 1(0,1), P = 0.007) than control group. Three months postoperatively, PVB group had lower rates of hypoesthesia (OR 0.28 (0.11, 0.75), P = 0.009), numbness (OR 0.26 (0.07, 0.88), P = 0.024) and sleep disorder (OR 0.84 (0.73, 0.97), P = 0.025) than control group.
Conclusions

Intermittent bolus paravertebral block provided anesthetics- and opioids-sparing effects, and enhanced recovery both in hospital and after discharge in patients receiving hepatectomy.
Entrainment of Chaotic Oscillations in a Colonial Tunicate.
Authors: Konrad Michael W.
Published: August 2021

BackgroundTunicates comprise an invertebrate, chordate subphylum which has been shown to be the closest group to vertebrates. Colonial tunicates are clusters of genetic clones generated asexually from a single free swimming larval “tadpole”. Each individual, or zooid, of the colony has a peristaltic heart which circulates blood through that individual. In addition, each zooid is connected to a common, external vascular network. This vascular network has radial extensions that end at the colony periphery in bulbs, or ampullae, which contract and expand to generate reciprocating flow between ampullae and zooids. Surgically detached ampullae continue to beat.ResultsQuantitative scans of videos of individual ampullae in a young Botrylloides viocella colony demonstrate ampullae contractions are often in phase, with occasional abrupt phase shifts out of and back to synchrony. The vessels connecting the ampullae to the zooid also contract, mostly in phase with the ampullae. Total volumes pumped by this colonial system are a significant fraction of the zooid volume, since it contracts 180 degrees out of phase and at the same frequency as the ampullae. Reversals of the peristaltic heart are at least partially synchronized with ampullae contractions. Ampullae that have been surgically detached from the colony contract at a more uniform rate with more symmetrical profiles than when part of the colony. ConclusionContractions of the ampullae and associated vessels pump sufficient blood in and out of the zooid that they should be considered functional hearts, and the partial synchrony of ampullae contractions results in a larger blood flow compared to an alternative asynchronous contraction pattern. The manner in which the ampullae abruptly fall out of and back to synchrony indicates synchrony is due to entrainment while the out of phase contractions of the zooid may be a direct result of pumping. The shape of contraction curves of detached ampullae pairs is almost indistinguishable from a pure sine wave, indicating that the more complex original pattern was due to interactions between out of phase ampullae. Ampullae and associated vessels might be analogous with the system of lymphatic vessels in vertebrates.
Design of a Chimaeric Antigen And Its Use In The Detection of IgG Antibodies Against Rubella Virus
Authors: Xing Wenyue , Li Li , Zhang Jingnan , Ma Chunli , Xue Xin , Hu Ruiping , Xue Huiting , Ye Shumei , Ma Yanhua , Yuan Hong
Published: August 2021

Background: Rubella virus (RV) is the causative agent of rubella or German measles. Although most infections cause only mild self-limited measles-like illness, the infection in pregnant women can cause severe foetal malformation or even miscarriage, especially in the first 3 months of pregnancy. Therefore, it is of great practical significance to establish a simple and sensitive RV detection method.Methods: The partial epitopes of the E1 and E2 proteins from Rubella Virus were selected as the target sites, the sequence of the selected antigenic sites of the E1 and E2 were linked by a linker. The expression plasmid P6T was constructed by inserting the gene into PET-32A + with a His tag. The P6 protein was induced and expressed in Escherichia coli L21 DE3 and purified by nickel column affinity. The protein P6 antigen was identified by Western blotting, and an anti-P6 antibody ELISA was established to test known serum samples to evaluate the capability of this method.Results: After purification, the concentration and purity of the protein P6 were 0.283 mg/mL and more than 80%, respectively. Western blotting showed that the protein P6 could react with rubella virus positive serum. By ELISA, 36 negative sera and 58 positive sera were detected. The coincidence rate, specificity and sensitivity of the ELISA were 88.89%, 84.48% and 84.48%, respectively. The P6 ELISA with a kappa coefficient of 0.709, P<0.05, indicated excellent consistency.Conclusions: The P6 protein with excellent antigenicity obtained from prokaryotic expression followed by chromatography purification could prove useful for early diagnosis of RV infection.
Seeds of phase transition to thermoacoustic instability
Authors: Manikandan Raghunathan , George Nitin Babu , Unni Vishnu , Sujith R. , Kurths Jürgen , Surovyatkina Elena
Published: August 2021

Tackling the problem of emissions is at the forefront of scientific research today. While industrial engines designed to operate in stable regimes produce emissions, attempts to operate them at "greener" conditions often fail due to thermoacoustic instability. During thermoacoustic instability, hazardous high amplitude periodic oscillations lead to failure of these engines in power plants, aircrafts and rockets. Yet, identifying the onset of thermoacoustic instability remains elusive due to spatial variability and the continuous evolution of spatiotemporal patterns in the reacting flow field. Here, we show experimental evidence of early manifestation of the onset of thermoacoustic instability at certain zones. Our findings allow us to identify a critical threshold that enables us to distinguish stable operating regimes from hazardous operations. This opens new perspectives for predicting the onset of thermoacoustic instability and could be a step forward to "greener" operations. The developed methodology is applicable for other systems exhibiting phase transitions.
Using a CO2 Laser-Firing as a Clean Production Method to Form an Electrical Conductivity Surface and Color-Changing on Craft Ceramic.
Authors: 李 (JAY)TZU-CHIEH 子介 LEE
Published: August 2021

Craft ceramic is an old industry. Most craft clay needs to be fired in a kiln, but kilns are expensive and inefficient [Kiln firing thermal efficiency: Kiln body heat storage 18.67%, Exhaust Sensible Heat 45.9%, Heat loss from incomplete combustion 16.24%, Radiated Conduction and Other Loss of Heat 12.61%]. In order to change the color of ceramic, potters commonly use kiln reduction firing. This technique requires an additional step and more fuel, which creates more air pollution. In this study, we used a CO2 laser to fire craft clay and glaze. This process not only changes the ceramic’s color but also changes the conductivity of the ceramic’s surface. By changing the composition of the glaze, the ceramic’s surface resistance was altered. Most kiln-fired ceramics are non-conductive because oxides are combined by covalent bonds. During the laser firing process, the covalent bonds become metal bonds. This new firing technique produces ceramic products that are superior in terms of light, heat, magnetism, and electricity. Thus, laser firing adds more function to the final ceramic product than kiln firing does. As opposed to kiln firing, there is no air pollution associated with CO2 laser firing. In comparison to kiln firing, laser-firing reduces both heat waste and air pollution by 99%. This study is based on our patented laser ceramic reduction firing technique. (Taiwan, R.O.C Patent Number: I687394) We recommend additional studies into laser firing in order to collect more data on laser-based ceramic production. Range: 20W laser
Integration of Transcriptome and Proteome Analysis Reveals the Mechanism of Freezing Tolerance in Winter Rapeseed
Authors: Wei Jiaping , Zheng Guoqiang , Dong Xiaoyun , Li Hui , Liu Sushuang , Wang Ying , Liu Zigang
Published: August 2021

Winter rapeseed seedlings are susceptible to low temperature during overwintering in Northwest China, leading to reduced crops production. Freezing stress is one of the utmost environmental stresses in Northwest China from late autumn to early spring, which are eventful for overwinter survival rate of winter rapeseed. However, the molecular mechanism of freezing tolerance formation is still very backward in winter rapeseed. In this study, using a pair of freezing-sensitive and freezing-resistant cultivars NQF24 and NTS57, the exhaustive effects of freezing stress on freezing tolerance formation were evaluated by analyzing leaf at the levels of transcriptome, proteome, physiology and ultrastructure. There were 8497 differentially expressed genes (DEGs) and 418 differentially abundant proteins (DAPs) specifically identified in leaf of NQF24 under freezing stress, while 7358 DEGs and 573 DAPs were specifically identified in leaf of NTS57. Function enrichment analysis showed that most of the enriched DEGs and DAPs were associated with plant hormones signal transduction, fatty acid metabolism, ribosome, plant-pathogen interaction and secondary metabolites biosynthesis. Freezing tolerance is formed by enhanced signals transduction, increased the biosynthesis of protein and secondary metabolites, higher reactive oxygen species (ROS) scavenging, more osmolytes, lower lipid peroxidation, and stronger ultrastructure. These results can be taken as selection indicators in freezing tolerance breeding program in rapeseed.
Effects of Blending Ratio and Processing of Lupine Bean On Nutritional Quality and Sensory Evaluation of Wheat-Lupine Bread
Authors: Alemu Tsehay , Woyraw Wubetu , Temesgen Habtamu , Abate Shimels
Published: August 2021

Background

Bread is one of the most popular and widespread baked products in the world. It is an important staple food made of wheat flour, salt, and yeast. However, wheat protein is lower than that of proteins from pulses. White lupine is a good source of protein, fiber, minerals, and vitamins. It has some anti-nutritional factors which inhibit its consumption. The use of lupine as human food, specifically in baked products has been limited.
Objective

This study was conducted to investigate the effect of blending ratio and processing of lupine bean on nutritional quality and sensory evaluations of wheat-lupine bread.
Methods

The study was done by factorial design. All white lupine bean was prepared in a randomized completely block design (RCBD). The quality characteristics of bread were analyzed by three-way ANOVA (Analysis of Variance) was carried out to determine the F-value and the level of significance, Duncan’s multiple range tests at 5% probability were used for the comparison between means using statistical tools of SPSS version 25.
Result

The effect of processing and blending ratio (140:10:15) had a high value in protein, fat, and mineral content. Sensory acceptance of wheat-lupine bread was affected by the interaction of blending ratio and processing. On a 5 point hedonic scale, the composite sample wheat flour with 5, 10, and 15% white lupine flour and supplementation had the highest scores were 4.60, 3.80, 3.80, 4.40, and 3.95 in color, taste, flavor, appearance, and overall acceptability respectively.
Development And Validation of A Pyroptosis -Related Signature And Immune Microenvironment Infiltration In Cutaneous Melanoma
Authors: Dalong Wei , Lan Xiaoling , Tang Qiang , Huang Zhiqun , Tang Qianli
Published: August 2021

Background: Cutaneous melanoma is cancer that is both malignant and aggressive, with a poor prognosis. Pyroptosis can affect the prognosis of cancer patients by controlling tumor cell growth, migration, and metastasis, as well as is closely related to the tumor immune microenvironment. The significance of pyroptosis-related genes (PRGs) in cutaneous melanoma, however, is unknown. Methods: The training set and external validation sets were cutaneous melanoma samples from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO), respectively. By using univariate Cox regression analysis and selection operator (Lasso) regression model, prognostic genes for overall survival (OS) were found. Candidate genes that were screened were used to calculate risk scores and construct a PRG risk model. The Kaplan Meier curve, time-dependent receiver operating characteristic (ROC) curve, and area under the curve (AUC)were used to assess the functional and prognostic usefulness of gene signatures in the risk model. Furthermore, to speculate on the activity of immune cell infiltration and immune-related pathways in the tumor immune microenvironment and calculate corresponding scores, a single sample gene set enrichment analysis (ssGSEA) was used.Results: An eight PRGs risk signature (AIM2, CASP4, CASP5, CASP8, IL18, NLRC4, NLRP6, PRKACA) were conducted and divided all cutaneous melanoma patients in the TCGA cohort into two groups: Low-risk and High-risk. Both the training and external validation sets showed that patients in the low-risk group showed a significantly higher likelihood of survival than those in the high-risk group (p < 0.001). Except for PRKACA, all the other eight PRGs in our study appeared to be longer survival times for patients. The results of ssGSEA in terms of 16 types of immune cells and the activity of 13 immune-related pathways showed that the High-risk group had lower immune pathway activity and lower levels of immune cell infiltration. In conclusion, the PRG-signature may be a significant predictor of prognosis and may play an essential role in UM patients' tumor immunity.
Synthesis, Antioxidant, Molecular Docking And DNA Interaction Studies of Metal Based Imine Derivatives
Authors: Ibrahim Muhammad , Ahmad Ashfaq , Perveen Fouzia , Nabi Hazrat Un , Muhammad Niaz , Ikram Muhammad , Ibrahim Musadiq , Ali Abid , Kamdem Jean Paul , M.Al-Swaidan Hassan , Rocha Teixeira
Published: August 2021

Background: Currently, numerous investigations are ongoing into the interaction of free radicals with biological systems such as lipids, DNA and protein. Methods: In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. Results: The metal complexes shown significant dose-dependent antioxidant activities comparable to the classical antioxidants, ascorbic acid and ethylene diaminetetraacetic acid (EDTA). The DNA binding constants (kb) were found to be 3.487×10-5M-1, 1.858×10-5M-1, 3.090×10-5M-1, 1.367×10-5M-1 and 9.118×10-5M-1 for Ni(II), Co(II), Cu(II) and Zn(II) metal complexes, respectively. Binding constants (Kb) and free energy (∆G) values calculated from molecular docking analysis were found to be in close agreement with experimental results.Conclusion: The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs.
High-Resolution Detection of Quantitative Trait Loci for Seven Important Yield Components in Wheat (Triticum aestivum L.) using a High-Density SALF-Seq Genetic Map
Authors: Li Tao , Li Qiao , Wang Jinhui , Yang Zhao , Tang Yanyan , Su Yan , Zhang Juanyu , Qiu Xvebing , Pu Xi , Pan Zhifen , Zhang Haili , Liang Junjun , Liu Zehou , Li Jun , Yang Wuyun , Yu Maoqun , Long Hai , Wei Yuming , Deng Guangbing
Published: August 2021

Background: Yield-related traits including thousand grain weight (TGW), grain number per spike (GNS), grain width (GW), grain length (GL), plant height (PH), spike length (SL), and spikelet number per spike (SNS) are greatly associated with wheat (Triticum aestivum L.) grain yield. To detect quantitative trait loci (QTL) associated with them, 193 recombinant inbred lines derived from two elite winter wheat varieties Chuanmai42 and Chuanmai39 were employed to perform QTL mapping in six or eight environments. Results: A total of 30 QTLs on chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 4A, 5A, 5B, 6A, 6D, 7A, 7B and 7D were identified. Among them, six major QTLs QTgw.cib-6A.1, QTgw.cib-6A.2, QGw.cib-6A, QGl.cib-3A, QGl.cib-6A, and QSl.cib-2D explaining 5.96-23.75% of the phenotypic variance were detected in multiple environments and showed strong and stable effects on corresponding traits. Three QTL clusters on chromosomes 2D and 6A containing 10 QTLs were also detected, which showed significant pleiotropic effects on multiple traits. Additionally, three Kompetitive Allele Specific PCR (KASP) markers linked to five of these major QTLs were developed. Candidate genes of QTgw.cib-6A.1/QGl.cib-6A and QGl.cib-3A were analyzed based on the spatiotemporal expression patterns, gene annotation, and orthologous search. Conclusions: Six major QTLs for TGW, GL, GW and SL were detected. Three KASP markers linked with five of these major QTLs were developed. These QTLs and KASP markers will be useful for elucidating the genetic architecture of grian yield and developing new wheat varieties with high and stable yield in wheat.
Upper airway gene expression reveals a more robust innate and adaptive immune response to SARS-CoV-2 in children compared with older adults
Authors: Mick Eran , Tsitsiklis Alexandra , Spottiswoode Natasha , Caldera Saharai , Serpa Paula , Detweiler Angela , Neff Norma , Pisco Angela Oliveira , Li Lucy , Retallack Hanna , Ratnasiri Kalani , Williamson Kayla , Soesanto Victoria , Simões Eric , Kistler A. , Wagner Brandie , DeRisi Joseph , Ambroggio Lilliam , Mourani Peter , Langelier Charles
Published: August 2021

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults and only rarely in children. To investigate whether differences in the upper airway immune response could contribute to this disparity, we compared nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes (ISGs) was robustly activated in both children and adults with SARS-CoV-2 compared to the respective non-viral groups, with only relatively subtle distinctions. Children, however, demonstrated markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including TNF, IFNγ, IL-2 and IL-4 production. Cell type deconvolution confirmed greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibited a decrease in proportions of ciliated cells, the primary target of SARS-CoV-2, upon infection with the virus. These findings demonstrate that children elicit a more robust innate and adaptive immune response to SARS-CoV-2 infection in the upper airway that likely contributes to their protection from severe disease in the lower airway.
Unexpected Favorable Outcome To Sintinib Monotherapy in A Relapse PDAC Patient With High TMB
Authors: zhang Fan , Li Xiaomin , liu haisheng , liu Rongfeng , zhou zhiguo , zhang Yi , chen Jingli , tian Ye , pan chaohu , Meng Qingju , Liu Yibing
Published: August 2021

Background Immune checkpoint inhibitors have not been widely used for pancreatic cancer treatment probably because of low immunogenic or stromal fibrotic tumor, among which only pembrolizumab was recommended for DNA mismatch repair deficiency (dMMR) by NCCN. Case presentation Here we report a 56-year-old man suffered from pancreatic ductal cancer (PDAC) with liver metastasis after radical surgery. NGS revealed remarkably high burden of TMB (49.92Muts/Mb) and microsatellite stability (MSS). Sintilimab monotherapy was continuously administrated after failure of combined chemotherapy, leading to stable disease within 22 months and few immunotherapy related AEs happened. Conclusions To our best knowledge, this is the first to report a good outcome achieving 22 months progression-free survival after PDAC metastasis with monotherapy of an immune checkpoint inhibitor. TMB may serve as a potential immunotherapy-related predictor in PDAC patients and help physicians make optimum clinical strategy.
Non-Traumatic Tile Type B3 Pelvic Fracture Combined With Garden Type III Femoral Neck Fracture Caused By Hypocalcaemia-Induced Convulsions
Authors: Dou Minghan , Ren Guangkai , Yuan Baoming , Peng Chuangang , Wu Dankai
Published: August 2021

BACKGROUND Non-traumatic fractures caused by convulsions are relatively rare and are often overlooked due to the lack of obvious evidence of injury. Non-traumatic fractures due to convulsions are diverse, but the concomitant of pelvic and femoral fractures has not been reported previously. CASE SUMMARY A 47-year-old woman with a no significant medical history, was taken to the nearest hospital after one episode of generalized tonic-clonic seizure that had occurred during sleep. After the postictal phase, the patient regained consciousness and experienced diffuse pain in the inguinal regions bilaterally with inability to stand or walk. The entire attack was witnessed by the family members who confirmed that there was not external trauma. Blood investigations revealed high creatinine and uric acid levels, along with a low calcium level. Conventional radiograph of the pelvis was performed to detect the cause of pain. The patient was noted to have a pelvic fracture and unilateral fracture of the neck of the femur. She was then transferred to our hospital for further management. The patient was diagnosed as having Tile type B3 pelvic fractures combined with a Garden type III femoral neck fracture on three-dimensional computed tomography (3D-CT). In view of her blood results, nephrology consultation was sought. The patient was identified as having a stage 5 chronic kidney disease (CKD), hypocalcemia, and hyperphosphatemia. However, neurological examination showed no abnormalities. No surgical intervention was adopted for her pelvic fractures. In addition to complete bed rest, closed reduction and percutaneous cannulated screw fixation was performed for the treatment of the right femoral neck fracture. An arteriovenous fistula was created for maintenance hemodialysis on the tenth postoperative day. At follow-up, twelve months follow-up after the operation, the patient had a normally gait and was satisfied with the outcome. CONCLUSION Patients who present with convulsive seizures especially patients with ion metabolism disorder should be examined thoroughly to ensure that no injury is missed.
Prediction of the rate of hand injuries in Singapore
Authors: Liau Glen Zi Qiang , Wong Joel Yat Seng , Tay Wei Xuan , Weng Jia Yi , Cheah Andre Eu Jin
Published: August 2021

Purpose

This study aims to analyze the correlation between the incidence rate of hand injuries and various construction and manufacturing indicators in Singapore. We hypothesize that the number of hand injuries is correlated to activity in the construction and manufacturing industries in Singapore.
Methods

20,764 patients who underwent hand surgeries in a tertiary institution between 2012 to 2018 were reviewed. Two independent, blinded observers extracted the frequency of hand surgeries performed from Electronic Medical Records. Economic indicators pertinent to Singapore’s labor force, construction and manufacturing industries were collected and smoothed by simple moving average of the prior 3 months. Results were analyzed using IBM SPSS v25.0.
Results

Significant independent univariate variables were Purchasing Manager Index for Manufacturing and Industrial Production Index. Multivariate regression of quarterly reported figures showed that Purchasing Manager Index for Manufacturing, Construction Index, Labor Productivity Change for Gross Domestic Product and Labor Productivity Change for Manufacturing were significantly correlated with hand injuries, with r square = 60.9%.
Conclusion

Quarterly economic indicators from construction and manufacturing industries can be used to predict the incidence of hand injuries with a 60.9% correlation. These findings may be useful for anticipating healthcare resource allocation to treat hand injuries.
Type of Study and Level of Evidence
Economic and decision, Level II.
Severe Radiological Manifestation in Patients with Diabetes and Pulmonary Tuberculosis: A Cross-sectional Study
Authors: Zhang Peize , Xiong Juan , Zhan Shenlin , Ren Tantan , Wang Yuxiang , Fu Liang , Deng Guofang
Published: August 2021

Purpose: Diabetes mellitus (DM) is believed to affect tuberculosis (TB) at multiple levels in disease control and treatment efficacy, but clinical and radiological presentation resulting from interaction of the two diseases is not known. We conducted a retrospective study to investigate how glycemic control impacts radiological and clinical manifestations in TB patients. Methods: A cross-sectional study was conducted on data obtained from medical records of 438 patients confirmed with TB-DM comorbidity at The Third people’s hospital of Shenzhen from April 1, 2014 to April 30, 2019. Their CT images were reviewed, and patients were divided into subgroups according to lung cavitation: with and without cavities, and number of segments showing pulmonary infiltration: <4 segment, 4-8 segment, >8 segment infiltrates. We then compared clinical parameters between these groups. Results: The median age of the patients was 50.0 years (IQR 43.3-56) and 86% (n=375) of them were male. Pulmonary cavities were found in 80.8% patients. 42.7% and 27.2% patients were seen to have infiltration involving 4-8 and >8 lung segments respectively. Patients presented with cavitation and infiltration involving a greater number of lung segments had significantly higher values of WBC, MONO%, GRA%, CRP, lower LYN% level and higher bacterial burden in sputum (P<0.001). Higher HbA1c and FBG were only observed in patients with lung cavities (P<0.001). There was no difference in positive ELISPOT.TB and PCT level between the groups regardless of presence or absence of lung cavity (P>0.9 and P=0.1 respectively). Lower HGB, ALB and higher PCT were observed in patients with infiltration involving more lung segments.Conclusion: Hyper-inflammation in peripheral blood was significantly associated with cavity and the number of lung lesions. Hyperglycemia was significantly associated with the development of lung cavity. Glycemic control and inflammation influenced radiographic manifestations in patients with TB-DM.
Complex Dynamics in an Eco-Epidemiological Model with the Cost of Anti-Predator Behaviors
Authors: Tan Yiping , Cai Yongli , Yao Ruoxia , Hu Maolin , Wang Weiming
Published: August 2021

In this paper, we investigate the complex dynamics of a predator-prey model with disease in the prey, which is characterized by the reduction of prey growth rate due to the anti-predator behavior. The value of this study lies in two aspects: Mathematically, it provides the existence and the stability of the equilibria and gives the existence of Hopf bifurcation. And epidemiologically, we find that the influence of the fear factor is complex: (i) the level of the population density decreases with the increasing of the fear factor; (ii) the cost of fear can destabilize the stability and benefit the emergency of the periodic behavior; (iii) the high level of fear can induce the extinction of the predator. These results may enrich the dynamics of the eco-epidemiological systems.
Stalled at the Intersection: Insurance Status and Disparities in Post Mastectomy Breast Reconstruction
Authors: Friedman-Eldar Orli , Burke Jonathan , Silva Iago de Castro , Baumrucker Camille C , Valle Fernando , Lessard Anne-Sophie , Kassira Wrood , Franceschi Dido , Kesmodel Susan B , Avisar Eli , Goel Neha , Möller Mecker G
Published: August 2021

PurposePost-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety net hospital and a private academic center.MethodsData were collected on all patients who underwent mastectomy for breast cancer from 2011-2019 in a private academic center and an adjacent public safety-net hospital served by same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors.ResultsOf 1,554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR. Out of them, 741 had insurance type recorded, with 592 (79.9%) privately insured patients, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured patients. Multivariable logistic regression showed a significantly lower likelihood of undergoing PMBR for uninsured (OR 6.9, 95% CI: 4.1-11.7; p<0.0001), Medicare (OR 2.0, (5% CI: 1.2-3.3; p=0.004), and Medicaid (OR 1.7, 95% CI:1.1-2.7; p=0.02) patients, compared with privately insured patients. Age, stage, race, and hospital type confounded this relationship.ConclusionPatients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.
Control of Difference of Seismic Response Across Different Spans of High-Speed Railway Multi-Spans Simply Supported Bridge
Authors: Zhang Yuntai , Jiang Lizhong , Zhou Wangbao , Lai Zhipeng , Liu Xiang , Peng Kang , Wang Zheng , Feng Yulin
Published: August 2021

In this paper, the Difference of Seismic Response across Different Spans (DSR) in the longitudinal distribution of High-Speed Railway Multi-spans Simply Supported Bridge (HSRSB) under longitudinal earthquake excitation is investigated, and an evaluation method which can intuitively reflect the difference of seismic response is proposed. A feasible way to strengthen the connection stiffness between adjacent girders is proposed to control DSR. The rationality of the finite element model used is verified by comparing the numerical results with the experimental ones, showing a satisfactory agreement. Comparing the seismic response of a bridge model considering the subgrade-track constraints (BCTM) and a bridge model without subgrade-track constraints (BWTM), it is found that the DSR in the longitudinal distribution causes some new disadvantages, which are neglected in BWTM. The BCTM considering DLC generates a model called BCDM. The effect of the number of span on DSR are studied based on BCDM. The analysis of this model showed that DLC suppresses the DSR and reduces the seismic response of most bridge components. It also transfers the seismic disadvantage from the bridge part to the subgrade-track structure. As it is more convenient and cost-effective to repair the base plate of the subgrade than the bridge components after earthquake seismic event, this disadvantage transfer is in favor of forming a new anti-seismic system that subgrade-track structure is used to protect the bridge part.
Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project
Authors: Cong Peikuan , Bai Weiyang , Li Jinchen , Yang Mengyuan , Khederzadeh Saber , Gai Sirui , Li Nan , Liu Yuheng , Yu Shihui , Zhao Weiwei , Liu Junquan , Sun Yi , Zhu Xiaowei , Zhao Pianpian , Xia Jiangwei , Guan Penglin , Qian Yu , Tao Jianguo , Xu Lin , Tian Geng , wang Pingyu , Xie Shu-Yang , Qiu Mochang , Liu Keqi , Tang Beisha , Zheng Hou-Feng
Published: August 2021

Imbalance of genetic resources in global population restricts the understanding of complex traits across populations. Here, we initiated the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (NGS) individuals and 5,841 high-density genotyping individuals. We identified 81.5 million SNPs and INDELs, of which 38.5% are novel. We found that 5.05% of the rare variants in WBBC were common in European population, and some trait-associated common variants in European had much lower allele frequency in Chinese. We provided a population-specific reference panel and an online imputation server (https://wbbc.westlake.edu.cn/) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we found novel selection signatures in SNX29, DNAH1 and WDR1 genes, and the selection of the alcohol metabolism genes (ADH1A and ADH1B) strengthened from about 4,000 years ago in East Asia. Genetic evidence supported the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separated the Han Chinese into subgroups, and we revealed that North Han was more homogeneous than South Han, and the history of effective population size of Lingnan began to deviate from the other three regions from 6,000 years ago. Significant selection of genes on epidermal cell differentiation was only observed in southern Chinese. Genetic divergence from north to south was more noticeable in the ancient than modern populations.
HPV and （ Neutrophil-to-lymphocyte ratio ） NLR are Prognostic Indicators of Laryngeal Cancer Patients Receiving Concurrent Chemoradiotherapy
Authors: Li Ke-jie , Lv Qi-yuan , Xu Yu-yan , Shao Zhen-yong , Zou Chang-Lin , Xie Rao-ying
Published: August 2021

Background and objectives: After receiving radical concurrent radiotherapy and chemotherapy, some patients with laryngeal cancer still have recurrence, and the recurrence time of different patients is different, which will pose a threat to the quality of life and survival of patients. The purpose of our study is to find out the factors that can predict the recurrence of laryngeal cancer, provide more accurate and individualized treatment for patients with laryngeal cancer, and improve the quality of life of patients.Methods：We collected follow-up data from 123 patients with laryngeal cancer who were admitted to the First Affiliated Hospital of Wenzhou Medical University between 2010 and 2015. These patients received only radical concurrent chemoradiotherapy after diagnosis. Univariate Cox analysis was used to find the factors related to Progression-free survival（PFS）in patients with laryngeal cancer. Multivariate Cox regression analysis was used to determine the factors and indicators that could predict patients' PFS. The Receiver Operating Characteristic curve（ROC curve） was used to determine the optimal truncation value of the forecast index.Results：Univariate Cox regression analysis showed that HPV, lymph node metastasis, NLR, （lymphocyte-to-monocyte Ratio）LMR and white blood cell count were related to PFS in patients with laryngeal cancer. Multivariate Cox regression analysis showed that positive HPV and NLR were effective predictors of PFS in laryngeal cancer. According to the ROC curve, the area under the curve of NLR is 0.743, and the optimal truncation value is 2.26.Conclusions：HPV and NLR are reliable predictors of PFS in patients with laryngeal cancer receiving concurrent chemoradiotherapy, which can provide help and suggestions for follow-up and individualized treatment of laryngeal cancer after treatment.
A Novel TMTP1-modified Theranostic Nanoplatform for Targeted in Vivo NIR-II Fluorescence Imaging-guided Chemotherapy of Cervical Cancer
Authors: Nuernisha Alifu , Ma Rong , Zhu Lijun , Du Zhong , Chen Shuang , Yan Ting , Alimu Gulinigaer , Zhang Linxue , Ma Cailing , Zhang Xueliang
Published: August 2021

BackgroundNear-infrared II (NIR-II, 900-1700 nm) fluorescence bioimaging with advantages of good biosafety, excellent spatial resolution, high sensitivity and contrast, has attracted great attentions in biomedical research fields. However, most nanoprobes used for NIR-II fluorescence imaging have poor tumor-targeting ability and therapeutic efficiency. To overcome these limitations, a novel NIR-II-emissive theranostic nanoplatform for imaging and treatment of cervical cancer was designed and prepared. The NIR-II-emissive dye IR-783 and chemotherapy drug doxorubicin (DOX) were encapsulated into liposomes, and the tumor-targeting peptide TMTP1 was conjugated to the surface of the liposomes to form IR-783-DOX-TMTP1 nanoparticles (NPs) via self-assembly methods.ResultsThe IR-783-DOX-TMTP1 NPs showed strong NIR-II emission, excellent biocompatibility, a long lifetime, and low toxicity. Further, high-definition NIR-II fluorescence microscopy images of ear blood vessels and intratumor blood vessels were obtained from IR-783-DOX-TMTP1 NPs-stained mice with high spatial resolution under 808 nm laser excitation. Moreover, IR-783-DOX-TMTP1 NPs showed strong tumor targeting ability and high efficiently chemotherapeutic character towards cervical tumors. ConclusionsThe novel targeting and NIR-II-emissive IR-783-DOX-TMTP1 NPs have potential in diagnosis and therapy for cervical cancer.
Structural Insight into PRMT5 Inhibitors through Amalgamating Pharmacophore-Based Virtual Screening, ADME-Toxicity and Binding Energy Studies and Identify New Inhibitors by Molecular Docking.
Authors: Bathula Revanth , Sivan Sree kanth , Somadi Gururaj , Muddagoni Narasimha , Lanka Goverdhan , Potlapally Sarita Rajender
Published: August 2021

Protein arginine methyltransferase 5 (PRMT5) is a member of the methyltransferases family, a type II arginine enzyme that is crucial for many cellular processes and is associated with many cancer diseases. In this study, pharmacophore-based 3D QSAR modeling, virtual screening and binding free energy studies were carried out from a set of 61 potent compounds reported being inhibitors of PRMT5 protein. A five-point pharmacophore model (AADHR) was generated and this model is used to generate an atom-based 3-Dimensional quantitative structure-activity relationship (3D-QSAR). The obtained 3D-QSAR model has high correlation coefficient (R2 = 0.91), cross-validation coefficient (Q2 = 0.82), F value (140.3), low RMSE (0.47) and pearson R-value (0.91). A library of 329825 molecules (ChEMBL database) is screened with pharmacophore model to retrieve hit molecules that are further subjected for molecular docking to identify best fit-active conformations binding at the receptor site of PRMT5 protein. Further, we are calculated ADME and toxicity properties using QikProp module and pkCSM server and finally prioritized the lead molecules by binding free energy prediction.
Changes in Trophic Structure of An Exploited Fish Community At The Centennial Scale Are Linked To Fisheries and Climate Forces
Authors: Durante Leonardo , Wing Stephen , Ingram Travis , Sabadel Amandine , Shima Jeffrey
Published: August 2021

Understanding how marine food webs are affected by anthropogenic stressors is an important steppingstone toward the improved management of natural resources. Stable isotope analysis of historical and modern samples spanning a century indicated that the niche breadth of an exploited fish community increased after the expansion of New Zealand fisheries. Since the 2000s most species increased their reliance on food webs supported by pelagic production and shifted to a higher trophic level. Overall changes were coincident with ocean warming, climate oscillations, prey abundance and fishing intensity, but their effects were specific to each fish assemblage analyzed. Data derived from historical samples revealed how anthropogenic stressors can drive long-term shifts in the trophic structure of an exploited fish community.
Correlated interlayer exciton insulator in double layers of monolayer WSe2 and moiré WS2/WSe2
Authors: Zhang Zuocheng , Regan Emma , Wang Danqing , Zhao Wenyu , Wang Shaoxin , Sayyad Mohammed , Yumigeta Kentaro , Watanabe Kenji , Taniguchi Takashi , Tongay Sefaattin , Crommie Michael , Zettl Alex , Zaletel Michael , Wang Feng
Published: August 2021

Moiré superlattices in van der Waals heterostructures have emerged as a powerful tool for engineering novel quantum phenomena. Here we report the observation of a correlated interlayer exciton insulator in a double-layer heterostructure composed of a WSe2 monolayer and a WS2/WSe2 moiré bilayer that are separated by an ultrathin hexagonal boron nitride (hBN). The moiré WS2/WSe2 bilayer features a Mott insulator state at hole density p/p0 = 1, where p0 corresponds to one hole per moiré lattice site. When electrons are added to the Mott insulator in the WS2/WSe2 moiré bilayer and an equal number of holes are injected into the WSe2 monolayer, a new interlayer exciton insulator emerges with the holes in the WSe2 monolayer and the electrons in the doped Mott insulator bound together through interlayer Coulomb interactions. The excitonic insulator is stable up to a critical hole density of ~ 0.5p0 in the WSe2 monolayer, beyond which the system becomes metallic. Our study highlights the opportunities for realizing novel quantum phases in double-layer moiré systems due to the interplay between the moiré flat band and strong interlayer electron interactions.