bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Morphometry and Chromatin Texture Changes in Hepatocellular Carcinoma Samples May Predict Liver Transplant Patients’ Outcomes
Authors: Santos Jordan Boeira dos , Starosta Rodrigo Tzovenos , Pilar Emily Ferreira Salles , Kunz Jefferson Daniel , Tomedi Joelson , Cerski Carlos Thadeu Schmidt , Ruppenthal Rúbia Denise
Published: February 2022

Background: Nuclear changes are typical in the carcinogenesis of hepatocellular carcinoma (HCC). Morphometry and chromatin texture analysis are quantitative methods for their quantification. In this study, we analyzed nuclear morphometry and chromatin texture parameters in samples of hepatocellular carcinoma from liver transplant patients and their associations with clinicopathologic variables. Methods: Samples of HCC and adjacent tissue from 34 individuals were collected in tissue microarray blocks. Stained slides were microphotographed using an optical microscope and nuclear parameters analyzed in ImageJ (FracLac plug-in). ROC curve analysis was used to find accurate cut-offs for differentiation of neoplastic and non-neoplastic cells. The inter-rater agreement was also evaluated. Results: Nuclear morphometric and textural differences were observed between the samples of HCC and adjacent tissue of liver transplant patients. Lower mean gray value (p=0.034) and Feret diameter (p=0.024) were associated with higher Model for End-Stage Liver Disease (MELD) scores. Nuclei with larger area (p=0.014) and Feret diameter (p=0.035) were associated with lower survival. Lower aspect ratio was associated with HCC recurrence after the transplant (p=0.048). The cut-off of 1.13μm (p=<0.001) for aspect ratio and cut-off of 21.15μm (p=0.038) for perimeter were established for the differentiation of neoplastic and non-neoplastic cells. The morphometric analysis was reproducible to area, circularity, Feret diameter, mean gray value and aspect ratio between observers (p=<0,001). Conclusions: Nuclear morphometric differences between the HCC and the adjacent tissue samples were associated with prognostic variables (MELD scores, recurrence and survival) and may predict liver transplant patients’ outcomes.
Ultrasound-Based Radiomics Analysis for Preoperative Prediction of Central and Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Multi-Institutional Study
Authors: Tong Yuyang , Zhang Jingwen , Wei Yi , Yu Jinhua , Zhan Weiwei , Xia Hansheng , Zhou Shichong , Wang Yuanyuan , Chang Cai
Published: February 2022

Background

An accurate preoperative assessment of cervical lymph node metastasis (LNM) is important for choosing optimal therapeutic strategy for papillary thyroid carcinoma (PTC) patients. This study aimed to develop and validate two ultrasound (US) nomograms for the individual prediction of central and lateral compartment LNM in patients with PTC.
Methods

A total of 720 PTC patients from 3 institutions were enrolled in this study. They were categorized into a primary cohort, an internal validation, and two external validation cohorts. Radiomics features were extracted from conventional US images. LASSO regression was used to select optimized features to construct the radiomics signature. Two nomograms integrating independent clinical variables and radiomics signature were established with multivariate logistic regression. The performance of the nomograms was assessed with regard to discrimination, calibration, and clinical usefulness.
Results

The radiomics scores were significantly higher in patients with central/lateral LNM. A radiomics nomogram indicated good discrimination for central compartment LNM, with an area under the curve (AUC) of 0.875 in the training set, the corresponding value in the validation sets were 0.856, 0.870 and 0.870, respectively. Another nomogram for predicting lateral LNM also demonstrated good performance with a training AUC of 0.938, an internal validation AUC of 0.905, and two external validation AUC of 0.881 and 0.903, respectively. The clinical utility of the nomograms was confirmed by the decision curve analysis.
Conclusion

The nomograms proposed here have favorable performance for preoperatively predicting cervical LNM, and hold promise for optimizing the personalized treatment, which may improve the survival outcome in PTC patients.
Individualized Prognostic Score for Lung Adenocarcinoma Based on Immune Status
Authors: Chen Peng , Abdurazik Mihray , Huo Gengwei , Du Ye , Zuo Ran , Zhu Fuyi , Cui Jinfang , Yuan Dongqi
Published: February 2022

Background: Lung adenocarcinoma (LUAD) is the prevalent non-small cell lung cancer (NSCLC) histological subtype, with rising morbidity and mortality. This study was conducted with the motive to develop a prognostic model by examining the relation between immune-related gene (IRGs) profiles.Methods: We combined immune-related gene (IRG) expression profiles and progression-free intervals (PFIs) in 594 LUAD patients by using TCGA dataset. The COX regression analysis and computational difference technique were used to predict survival-associated and differentially expressed IRGs in LUAD patients. Computational biology was also used to investigate the characteristics and molecular mechanisms of these LUAD-specific IRGs. Using multivariable COX analysis, a novel prognostic index based on immune-related genes was established.Results: There was a strong correlation between the clinical outcome of LUAD patients and 58 differentially expressed immune-related genes. These genes were found to be actively involved in a KEGG pathway involving cytokines and cytokine receptors, as demonstrated by functional enrichment analysis. A prognostic signature comprised of IRGs (CRABP1, S100A16, FGF2, RBP2, FURIN, SLC11A1, ANGPTL4, VIPR1, BDNF, IL11, INHA, SEMA4B, TNFRSF11A) performed relatively well in prognostic prediction and was associated with tumour stage, tumour burden, age, number of lesions, and metastasis. Surprisingly, the IRG-based prognostic index effectively predicted immune cell infiltration.Conclusions: Our findings collectively identified multiple clinically relevant IRGs, identified regulators of the immunological repertoire, as well as established the critical role of a tailored, surveillance, IRG-based immune signature in the diagnosis, and prognosis of LUAD.
Severe Combined Immunodeficiency (SCID) Screening in Arizona: Lessons Learned from the First 2 Years
Authors: Booth Natalie A , Freeman Catherine M , Wright Benjamin L , Rukasin Christine , Badia Priscila , Daines Michael , Bauer Cindy S , Miller Holly
Published: February 2022

Purpose:The incidence of severe combined immunodeficiency (SCID) in the United States was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of American Indian and Hispanic populations compared to national percentages. The true incidence of SCID and non SCID T-cell lymphopenia have not previously been reported in Arizona. Methods:A retrospective chart review was performed of abnormal SCID Newborn Screening (NBS) tests from January 1, 2018 to December 31, 2019, using data from the Arizona Department of Health Service and the Phoenix Children’s Hospital’s electronic medical record [IRB# 20-025]. Results: Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis type SCID. Eighteen infants were identified with an abnormal initial NBS which ultimately did not lead to a diagnosis of SCID. Four of these infants were diagnosed with congenital syndromes associated with T-cell lymphopenia. Infants of Hispanic ethnicity were over-represented in this cohort. Conclusion: NBS in Arizona confirmed an incidence more than 2.5 times that reported nationally. This increased incidence is likely reflective of Arizona’s unique population profile, with a higher percentage of American Indian population. The findings in our non-SCID cohort are in alignment with previously published data, except for a higher than anticipated number of infants of Hispanic/Latino ethnicity, likely related to Arizona’s higher percentage of Hispanic/Latino population.
Therapeutic Effects of Tocotrienol-Rich Fraction on Rhinitis Symptoms in Platelet-Activating Factor Induced Allergic Rhinitis
Authors: Teo Cheryl Wei Ling , Png Stephanie Jia Ying , Ung Yee Wei , Yap Wei Ney
Published: February 2022

Background: Platelet-activating factor (PAF) has been suggested to be a potent inflammatory mediator in Allergic rhinitis (AR) pathogenesis. Vitamin E is known as a potential therapeutic agent for airway allergic inflammation. This study aimed to investigate the beneficial effects of palm-derived Tocotrienol-rich fraction (TRF) on PAF-induced AR in a rat model. Methods: Sprague Dawley rats were randomly assigned into 3 groups: Control, PAF-induced AR and PAF-induced AR with TRF treatment. To induce AR, 50 μl of 16 μg/ml PAF was nasally instilled into each nostril. From day 1 to 7 after AR induction, 10 μl of 16 μg/μl TRF was delivered intranasally to the TRF treatment group. Complete upper skulls were collected for histopathological evaluation on day 8.Results: The average severity scores of AR were significantly higher in the PAF-induced AR rats compared to both control and PAF-induced AR with TRF treatment. The histologic examination of the nasal structures showed moderate degree of inflammation and polymorphonuclear cells infiltration in the lamina propria, mucosa damage and vascular congestion in the PAF-induced AR rats. TRF was able to ameliorate the AR symptoms by restoring the nasal structures back to normal. H&E staining demonstrated a statistically significant benefit upon TRF treatment, where minimal degree of inflammation, and a reduction in the infiltration of polymorphonuclear cells, mucosa damage and vascular congestion were observed. Conclusion: TRF exhibited symptomatic relief action in AR potentially due to its antioxidant, anti-inflammatory and anti-allergic properties.
Identification of Prostate Cancer Subtypes Based on Immune Signature Scores in Bulk and Single Cell Transcriptomes
Authors: Chen Canping , Wang Xiaosheng
Published: February 2022

Prostate cancer (PC) is heterogeneous in the tumor immune microenvironment (TIME). Subtyping of PC based on the TIME could provide new insights into intratumor heterogeneity and its correlates of clinical features. Based on the enrichment scores of 28 immune cell types in the TIME, we performed unsupervised clustering to identify immune-specific subtypes of PC. The clustering analysis was performed in ten different bulk tumor transcriptomic datasets and in a single cell RNA-Seq (scRNA-seq) dataset, respectively. We identified two PC subtypes: PC immunity high (PC-ImH) and PC immunity low (PC-ImL), consistently in these datasets. Compared to PC-ImL, PC-ImH displayed stronger immune signatures, worse clinical outcomes, higher epithelial-mesenchymal transition (EMT) signature, tumor stemness, intratumor heterogeneity (ITH) and genomic instability, and lower incidence of TMPRSS2-ERG fusion. Tumor mutation burden (TMB) showed no significant difference between PC-ImH and PC-ImL, while copy number alteration (CNA) was more significant in PC-ImL than in PC-ImH. PC-ImH could be further divided into two subgroups, which had significantly different immune infiltration levels and clinical features. In conclusion, “hot” PCs have stronger anti-tumor immune response while worse clinical outcomes versus “cold” PCs. CNA instead of TMB plays a crucial role in the regulation of TIME in PC. TMPRSS2-ERG fusion correlates with decreased anti-tumor immune response while better disease-free survival in PC. The identification of immune-specific subtypes has potential clinical implications for PC immunotherapy.
Evaluation of Polychlorinated biphenyls (PCBs) in Iranian dairy products (yogurt, doogh and kashk) by modified QuEChERS extraction and GC- QqQ-MS/MS method: a health risk assessment study
Authors:   Amin Kiani1 Amin Kiani1, Arabameri Majid , Moazzen Mojtaba , Shariatifar Nabi , Tooryan Fahimeh , Ghanbariasad Ali , Shahsavari Saeed
Published: February 2022

The levels of 6 NDL-PCBs (non-dioxin-like-polychlorinated biphenyls) of were measured in some of Iranian dairy products (yogurt, doogh and kashk). A total of 120 samples were evaluated by modified QuEChERS extraction and gas chromatography-triple-quadrupole mass spectrometry (GC-QqQ-MS/MS) method, also RSD and recovery were determined, 6.33–8.86 and 97.45–102.63 %, respectively. The outcomes of our research exhibited the average levels of Ʃ6-NDL-PCBs in all samples were 15.17±3.44 ng/g fat that were lower than the standard level established by EU (40 ng/g fat). Also, results showed kashk samples had maximum mean level of 6-NDL-PCBs (18.66±2.42 ng/g fat) and doogh samples had minimum mean level of 6-NDL-PCBs (12.21±2.22 ng/g fat). The mean level of 6-NDL-PCBs in yogurt samples was 14.65±2.02 ng/g fat. The heat map results depicted the correlation between spectral indicators 6-NDL-PCBs in different dairy products. A risks assessment based on the Monte Carlo method was done by calculating the Estimated Daily Intake (EDI) and Incremental Life Cancer Risk (ILCR) by the technique of Monte Carlo. The EDI values of 6 NDL-PCBs based on the 95 percentile in yogurt, doogh and kashk were 14.3, 1.49 and 0.5 ng/kg.day, respectively. According to the calculated 95 percent ILCR, dietary exposure to 6 NDL-PCBs does not pose a risk to Iranian consumer health.
The Signature of Glycometabolism-Related Genes in Predicting the Prognosis of Patients with Osteosarcoma
Authors: Wang Fengyan , Yang Kun , Li Ke , Peng Guoxuan , Yang Hua , Xiang Yang , Sun Hong
Published: February 2022

Background
Osteosarcoma is a primary malignant bone tumor with high metastatic potential and an inferior prognosis. Glycometabolism also plays a role in the disease. However, the clinical significance of glycometabolism-related genes in patients with osteosarcoma has been unclear.
Methods
We downloaded the expression profile and corresponding clinical data of osteosarcoma samples from database. Glycometabolism-related gene sets were obtained. Regression analyses were performed to construct a glycometabolism-related prognostic gene signature. The. independent prognostic value of the signature was further assessed by univariate and multivariate Cox regression analysis, and the correlation between immune cells and the signature was investigated. The regulatory mechanism of the prognostic genes was explored by constructing a ceRNA network.
Results
A glycometabolism-related prognostic gene signature based on PRKACB, SEPHS2, GPX7, and PFKFB3 was constructed, and the survival and receiver operating characteristic curves showed that the glycometabolism-related gene signature had a good performance in predicting the overall survival of patients with osteosarcoma. Univariate and multivariate Cox regression analyses confirmed that the glycometabolism-related gene signature was an independent prognostic factor among patients. Correlation analysis revealed that SEPHS2, PRKACB, and GPX7 were correlated with immune cells. A ceRNA network comprised of four genes, 148 miRNAs, and 91 lncRNAs was constructed.
Conclusions
A novel signature based on four glycometabolism-related genes, was constructed, which may facilitate the prognosis and treatment of osteosarcoma in clinical practice.
Fire Simulation and Emergency evacuation simulation of college student apartment
Authors: XIAO Mufeng , ZHOU Xihua , WANG Jue , YU Haibo , HAN Baoxin , GAO Jialu , HAN Yanchun , WANG Yanan
Published: February 2022

The relative concentration of personnel in student apartments in colleges and frequent safety incidents have seriously affected the lives and property safety of students.Therefore, it is of great significance to study the fire in college apartments and its emergency evacuation.Based on the size and volume of No. 4 student dormitory building in the North Campus of Liaoning Technical University,this study use Pyrosim software to carry out fire numerical simulation. The variation rules of smoke visibility, CO concentration, and ambient temperature in the college student apartment building were analyzed and the available safe evacuation time was determined. Moreover, the Pathfinder software was used to carry out emergency evacuation simulation with the combination of physical signs, evacuation speed and personnel proportions, etc.It can analyze the influence of factors such as the number of evacuated persons on each floor of the college student apartment and the layout of the building's staircase on the evacuation time.The result shows:visibility change characteristics have a greater impact on evacuation and rescue;the original layout of the student apartment cannot satisfy the safe evacuation of all personnel;the bottleneck areas for emergency evacuation are indoor corridors and evacuation stairs;increasing the number of evacuation exits in the stairwell can effectively improve the efficiency of escape;when the number of students on each level reaches a certain value, restrictions must be taken, etc.The research results can provide a basis for the reasonable planning and management of evacuation passages in college student apartments.
HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ARPC1B DEFICIENCY
Authors: Giardino Stefano , Volpi Stefano , Lucioni Federica , Caorsi Roberta , Schneiderman Jennifer , Lang Abigail , Khojah Amer , Kuijpers Taco , Papadatou Ionanna , Paisiou Anna , Alonso Laura , Schulz Ansgar , Nufar Marcus , Gattorno Marco , Faraci Maura
Published: February 2022

Mutations in the component isoform ARPC1B of Human actin-related protein 2/3 complex have been recently associated with combined immunodeficiency related to impaired T-cell function, allergies, autoinflammation, and platelets abnormalities. Currently, indications on the management of this novel disease and information on its outcome are lacking. We report the first case series of 7 children who underwent allogeneic-HSCT (allo-HSCT) with homozygous mutation in ARPC1B gene.All patients presented an early clinical onset, complicated with neonatal hemorrhagic enteritis in 3 and macrophage activating syndrome in 2, characterized by recurrent infections, failure to thrive and gastrointestinal bleeding episodes. Allo-HSCT was performed at the median age of 3.54 years after a myeloablative conditioning regimen in all cases. Engraftment occurred in all patients with a full donor chimerism in 6 out of 7. The clinical course after engraftment was uneventful in 3 out of 7 children; two developed a grade 1-2 acute Graft-versus-Host Disease (GvHD), 1 of them a grade 1 chronic-GvHD. Progressive multifocal leukoencephalopathy JC virus-related was diagnosed in one patient 13 months after haploidentical-HSCT, successfully managed with donor-derived viral-specific T-cell infusion. Only one patient had a severe outcome with veno-occlusive disease and transplant-associated microangiopathy and died 3 months after HSCT because of a sepsis. At a median follow-up of 19 months (range 3 – 110), 6 out of 7 patients are alive and disease free.The severe clinical phenotype at diagnosis and the high survival rate with limited transplant-related morbidity reported strongly support the indication to allo-HSCT for patients with this diagnosis.
Speaking COVID-19: Supporting COVID-19 communication and engagement efforts with people from Culturally and Linguistically Diverse Communities
Authors: Seale Holly , Harris-Roxas Ben , Heywood Anita , Abdi Ikram , Mahimbo Abela , Chauhan Ashfaq , Woodland Lisa
Published: February 2022

Background

Since the emergence of COVID-19, issues have been raised regarding the approach used to engage with culturally, and linguistically diverse (CaLD) communities during this public health crisis. This study aimed to understand the factors impacting communication and engagement efforts during the COVID-19 pandemic from the perspective of key CaLD community stakeholders and opinion leaders.
Methods

Forty-six semi-structured telephone interviews were undertaken with key stakeholders who have an active role (established prior to the pandemic) in the delivery of services and other social support to CaLD communities in Australia.
Results
Seven key themes emerged: (1) the digital divide and how to really connect with people; (2) information voids being filled by international material; (3) differentiating established with new and emerging community needs; (4) speaking COVID-19; (5) ineffectiveness of direct translations of English language resources; (6) Coordination is needed to avoid duplication and address gaps and (7) recognising the improvements in governments’ approach.
Conclusion

It is critical that alliances be set up that can be activated in the future to reduce issues around resource development, translation, and dissemination of messages to minimise gaps in the response. Financial assistance must be provided in a timely way to community organisations to support the development and dissemination of culturally appropriate communication materials.
Percutaneous Mesh-container-plasty (PMCP) Versus Percutaneous Kyphoplasty (PKP) in the Treatment of Spinal Metastases: a Retrospective Cohort Study.
Authors: Li Yimin , Qian Yunfan , Shen Guangjie , Tang Chengxuan , Zhong Xiqiang , HE Shaoqi
Published: February 2022

Background: To compare the clinical and radiological results of percutaneous mesh-container-plasty (PMCP) versus percutaneous kyphoplasty (PKP) in the treatment of spinal metastases.Methods: Patients with confirmed diagnosis of spinal metastases and treated in our center between January 2011 and December 2019 were retrospectively included in the study. Ninety-four Patients were divided into 2 groups (PKP 50 and PMCP 44) according the surgical treatment they received. The epidemiological data, surgical outcomes, and clinical and radiological features were compared between the two groups. Cement leakage, height restoration, deformity correction, and cement distribution were calculated from the radiographs. The visual pain analog scale (VAS), Oswestry disability index (ODI), and Karnofsky performance scale (KPS) scores were calculated before surgery, and immediately and 2 years after surgery.Results: The VAS, ODI, and KPS scores improved from 5 (4–6), 65.24±6.59, and 40 (40–50) preoperatively to 2 (1–2), 21.68±4.38, and 70 (70–80) immediately postoperatively in the PKP group (p < 0.05), and from 5 (4–6), 66.45±6.04, and 40 (40–50) preoperatively to 1 (1–2), 21.91±3.88, and 70 (70–80) immediately postoperatively in the PMCP group (p < 0.05), respectively; there was no significant difference between the two groups. The mean cost in the PKP group was lower than that in the PMCP group (5563±439 vs. 6569±344, p < 0.05). Cement distribution in the PMCP group was higher than that in the PKP group (44.30% ± 10.25% vs. 32.54% ± 11.76%, p < 0.05). Cement leakage was observed to be lesser in the PMCP group (7/44) than in the PKP group (18/50, p < 0.05). There were no statistically significant differences in the recovery of vertebral body height and improvement of segmental kyphosis between the PMCP and PKP groups in the treatment of spinal metastases. Conclusions: Both PKP and PMCP have significant abilities in pain relief, functional recovery, height restoration, and segment kyphosis improvement. Despite its higher cost, PMCP may have a better ability to inhibit cement leakage and cement distribution than PKP in the treatment of spinal metastases.
UV-cured coatings for highly efficient passive all-day radiative cooling
Authors: Luo Heng , Yang Meng , Guo Jing , Zou Weizhi , Xu Jian , Zhao Ning
Published: February 2022

Passive radiative cooling provides a promising way to reduce energy consumption for cooling. However, it always requires stringent materials designs or manipulations, which are neither cost-effective nor widely adaptable. Here, we report a fast, inexpensive, and scalable UV-curing method to fabricate porous polymer coatings via photopolymerization-induced phase separation. This coating with hierarchical pore structure, has a superior long-wave infrared emittance of 0.98 and strong solar reflectance of 0.96, resulting in sub-ambient temperature drops of ~9.8°C during the night and ~5.7°C under solar intensity of ~960 W m−2 in the metropolitan area in summer. Moreover, the UV-cured coating is highly crosslinked and superhydrophobic without any treatment, showing excellent durability after long-term UV irradiation, thermal aging, or immersion in corrosive chemicals. The paint-like simplicity and remarkable weather resistance are vital for promoting practical applications of cooling coatings.
Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform
Authors: Naranjo Santiago , Cabana Christina , LaFave Lindsay , Westcott Peter , Romero Rodrigo , Ghosh Arkopravo , Liao Laura , Schenkel Jason , Priore Isabella Del , Jacks Tyler
Published: February 2022

Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD), the most common histological subtype, accounts for 40% of all cases. While autochthonous, genetically engineered mouse models (GEMMs) recapitulate the histological progression and transcriptional evolution of human LUAD, tumors in these models develop over several months and functional genomic studies are technically challenging. In contrast, cell line transplant models are fast and flexible, but these models fail to capture the full spectrum of disease progression. Organoid technologies provide a means to create next-generation cancer models that integrate the most relevant features of autochthonous and transplant-based systems. However, robust and faithful LUAD organoid platforms are currently lacking. Here, we describe optimized conditions to continuously expand murine alveolar type 2 cells (AT2), a prominent cell-of-origin for LUAD, in organoid culture. These organoids display canonical features of AT2 cells, including marker gene expression, the presence of lamellar bodies, and an ability to differentiate into the AT1 lineage. We used this system to develop flexible and versatile immunocompetent organoid-based models of KRAS, BRAF, and ALK-mutant LUAD. Notably, the resultant tumors closely resemble their autochthonous murine counterparts and human LUAD. In contrast to comparable organoid platforms, our system supports long-term maintenance of the AT2 cellular identity, providing unprecedented ease and reliability to study AT2 and LUAD biology in vitro and in vivo.
Complex Chronic Disease in Pediatrics – Needs in The Last Year of Life
Authors: Nogueira Andreia , Correia Diana , Loureiro Marisa , Gomes Barbara , Cancelinha Cândida
Published: February 2022

Published data on hospital use in the last year of life of a child with a life-threatening complex chronic disease (CCD) is scarce yet critical to inform the implementation phase of paediatric palliative care (PPC). We aimed to describe the last year of life of children with CCD, in terms of the clinic characteristics, hospital resources and the impact of referral to a hospital-based PPC team (PPCT). This is a quantitative, retrospective and comparative study of children with CCD (1–18 years of age), who died in a tertiary hospital between January 2016 and December 2020. We analysed the hospital resources in the last year, therapy and procedures in the last week of life, decision to limit treatment (DLT), place of death, referral to the PPCT and place to death, compared by number of CCDs. 72 patients (60% male) with a median age of 10.1 years were included. Most had ≥ 2 CCDs (58%) with cancer as the most common diagnosis (47%). The group with ≥ 3 CCD had longer hospital stays (p = 0.041). Of the 17 patients referred to the PPCT, there was a higher number of DLT (p < 0.001), greater use of the subcutaneous route (p < 0.001), a lower number of transfusions of blood products (p = 0.002) and a lower number of deaths in the Intensive Care Unit - ICU (p < 0.001). The ICU was the place where the highest number of deaths occurred (64% non-referred vs 6% referred, p < 0.001).Conclusion: Early implementation of PPC optimises the use of hospital resources, minimises invasive procedures and therapies and develops effective and sustainable alternatives which are better suited to the needs of children and/or families.
Genetic variation and population structure analysis of leymus Chinensis from eurasian steppes using SSR makers.
Authors: Ahmed Naseer , Hou Xianyang
Published: February 2022

Leymus chinensis is an essential perennial grass species extensively dispersed in the typical grassland communities of the Eurasian steppe region. It is relished by livestock due to its high quality and being a nutritionally valuable forage crop. Leymus chinensis has recently gained extensive consideration on its genetic diversity. However, genetic diversity studies on L. Chinensis using SSR markers is currently limited. In the present study, we investigate the genetic variation and population structure analysis of leymus chinensis from Eurasian steppes using SSR makers. For the genetic diversity, nineteen SSR markers were used and a total of 133 alleles were identified across the 166 L. Chinensis plants. Our findings illustrated that the polymorphic rate for all SSR markers was greater than 80%, with the exception of SSR12i and SSR6c, which had polymorphism rates of 50% and 75%, respectively. The gene diversity (H) ranged from 0.0545 for SSR12i to 0.4720 for SSR25v, and the average was 0.3136. Furthermore, genetic diversity analysis indicated that the 166 samples could be grouped into five main population clusters based on their maximum membership coefficients which were assigned as Pop1 to Pop5. Among the five populations, the largest values of allele (total number of detected alleles), Ne (effective number of alleles) and Na (observed mean number of alleles) was found to be higher in Pop1, with values of 61, 1.461, and 1.977, respectively. Additionally, AMOVA showed that 13% of the total genetic variation occurred among the population and 87% genetic variation within the populations of the species. Whereas, the pairwise Fst specified the moderate genetic variation ranging from 0.0336 to 0.0731. Finally, the principal coordinate analysis revealed that the x-axis and y-axis explained 5.72% and 4.86% of the variation in molecular data, respectively. Taken together, these SSR markers provide new insights for a more precise understanding of the genetic diversity of L. Chinensis germplasm and could potentially enhance the breeding program of L. Chinensis.
Diedaqili Tablet Promotes Bony Fusion Accelerates Fracture Healing In Mice
Authors: Zhao Ye , Zhang Yujie , Liu Kaoqiang , Yao Shen , Chai Yongli , Zhan Hongsheng , Yuan Weian , Shen Zhibi
Published: February 2022

Diedaqili tablet has been found effective for fracture healing in previous clinical studies. In a recent study, we investigated the effects of diedaqili tablet (DDQL) on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with a low dose (40.55mg/ ml), a high dose (162.18mg/ml) DDQL suspension and normal saline daily from day 1 after operation. The femur and blood of mice was analyzed by plain radiography, micro-computed tomography (Micro-CT), histology, biomechanical analysis, and serum Ca, P, and ALP test. The results demonstrated that DDQL can effectively improve the porosis of fracture end and bony union in the course of healing via Micro-CT and hematoxylin-eosin staining (HE staining) analysis. Consistent with morphological findings, biomechanical properties of fracture healing have also been demonstrated. And Diedaqili tablet has a dose-dependent effect. DDQL augmented the release of alkaline phosphatase (ALP) and phosphorus (P) into blood, indicating that it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during bone healing. In summary, the preliminary experiment revealed that DDQL can improve bone formation via promoting osteogenic capability, calcium (Ca) and P metabolism, and subsequently accelerates fracture repair and bony fusion.
Exploring the Potential Mechanism of Zhengan Xifeng Decoction for ischemic stroke based on Network pharmacology and Molecular Docking
Authors: Feng Xiaodong , Zhang Yasu , liu xiaomin , Long Junzi , Gao Qian , Pan Mengyang
Published: February 2022

Backgroud Ischemic stroke (IS) is an acute cerebrovascular incident that threatens public health. Zhengan Xifeng Decoction (ZXD), as a common herbal formula, has been widely applied in clinical practice for IS. The purpose of this study was to investigate the bioactive ingredients and potential pharmacological mechanisms of ZXD for IS based on network pharmacology and molecular docking.Methods Chemical ingredients of ZXD were screened from TCMSP, BATMAN-TCM and the literature. Then, the targets of the chemical ingredients were predicted through STITCH and SwissTargetPrediction databases. IS-related targets were selected from DisGeNET, DrugBank, MalaCards and GeneCards databases. And, the String database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were analyzed in Metascape. At last, Molecular docking was carried out using Open Babel GUI, AutoDock 1.5.6 and Pymol.Results 284 active ingredients involving 2353 putative targets were identified in ZXD, of which 1098 targets were linked to IS. A total of 20 core targets including MAPK3, MAPK1, and AKT1 were identified by analyzing PPI network. The biological process associated with IS were related to response to growth factor, apoptotic signaling pathway, MAPK cascade and neuron death. And KEGG enrichment included that Prolactin signaling pathway, VEGF signaling pathway and ErbB signaling pathway were closely correlated with neurogenesis, neurotransmission, synaptic plasticity vascular growth factor regulation, in IS. Finally, molecular docking revealed that core ingredients of Quercetin, Carvone and Asparamide had well-binding ability to core targets.Conclusion The study suggested that ZXD treated IS by modulating multiple targets and pathways. And, the results demonstrated that the mechanism of ZXD anti-IS may be related to the regulation of neuroprotection and angiogenesis through Prolactin signaling pathway, VEGF signaling pathway and the ErbB signaling pathway.
HbA1c Level is Associated with Heart Failure with Recovered Ejection Fraction in Type 2 Diabetic Patients
Authors: Yang Chen Die , Aihemaiti Muladili , Quan Jin Wei , Chen Jia Wei , Shu Xin Yi , Ding Feng Hua , Shen Wei Feng , Lu Lin , Zhang Rui Yan , Pan Wen Qi , Wang Xiao Qun
Published: February 2022

Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 385 T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after 6 to 12 months, which classified patients into HFrecEF or persistent HFrEF. Clinical outcomes of cardiovascular (CV) death and HF rehospitalization were analyzed during a mean of 3.3 years follow-up. Results: T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.1%~7.8%], P=0.001), especially in HF of ischemic etiology. After multivariate adjustment, every 1% increase in HbA1c conferred a 21.3% (OR: 0.787 [95% CI 0.658~0.933]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c≤6%), those with poor glycemic control (HbA1c > 8%) had higher risk of CV death or HF rehospitalization (HR: 2.778 [95% CI 1.470~5.251]). T2DM Patients with HFrecEF exhibited significantly better clinical outcomes than those with persistent HFrEF.Conclusions: This study demonstrates that T2DM patients with uncontrolled HbA1c levels were associated with compromised development of HFrecEF and worse clinical outcomes.
Transformation and Expression of Na+/H+ Antiporter Vacuolar (AgNHX1) Gene in Potato (Solanum Tuberosum L.) Plants Under Salt Stress
Authors: soliman hemaid Ibrahim , Kadasa Naif M S
Published: February 2022

Salinity is the main influencing factor in the productivity of most agricultural crops. Salinity has a negative effect on potato plants and yield. Previous research work shows that the transfer of the Na+/H+ antiporter gene to field crops improves the tolerance of plants to high salt concentrations. In this study, a vacuolar-type Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelinii (AgNHX1) was transferred into potato via Agrobacterium. Leaf explants induced callus on Murashige & Skoog's (MS) medium accompanied by NAA (2.00 mg l-1) and BAP (0.25 mg l-1). The in-vitro leaf generated the callus which was transferred to the regeneration medium containing ZR (2.00 mg l-1) and NAA (0.25 mg l-1). The stable integration of the AgNHX1 gene in genetically modified potato plants was confirmed by PCR analysis. RT-PCR and northern blot hybridization indicated that AgNHX1expressed highly in transgenic potato plants. Our results indicated that the expression of AgNHX1 enhanced the salt tolerance in transgenic potato plants with good growth. This happened because, under salt stress, the accumulation of Na+ content and proline was more in shoots as compared to control. It showed that the expression of AgNHX1 activity in genetically modified potato plants was four-fold higher than in unmodified potato plants. Thus, it can be said that AgNHX1 gene expression could increase salt tolerance in potato plants.
Using Empirical Biological Knowledge to Infer Regulatory Networks From Multi-omics Data
Authors: Pačínková Anna , Popovici Vlad
Published: February 2022

Background: Integration of multi-omics data can provide a more complex view of the biological system consisting of different interconnected molecular components, the crucial aspect for developing novel personalised therapeutic strategies for complex diseases. Various tools have been developed to integrate multi-omics data. However, an efficient multi-omics framework for regulatory network inference at the genome level that incorporates prior knowledge is still to emerge. Results: We present IntOMICS, an efficient integrative framework based on Bayesian networks. IntOMICS systematically analyses gene expression, DNA methylation, copy number variation and biological prior knowledge to infer regulatory networks. IntOMICS complements the missing biological prior knowledge by so-called empirical biological knowledge, estimated from the available experimental data. Regulatory networks derived from IntOMICS provide deeper insights into the complex flow of genetic information on top of the increasing accuracy trend compared to a published algorithm designed exclusively for gene expression data. The ability to capture relevant crosstalks between multi-omics modalities is verified using known associations in microsatellite stable/instable colon cancer samples. IntOMICS is also applied to detect potential predictive biomarkers in microsatellite stable stage III colon cancer samples. Conclusions: We provide IntOMICS, a framework for multi-omics data integration using a novel approach to biological knowledge discovery. IntOMICS is a powerful resource for exploratory systems biology and can provide valuable insights into the complex mechanisms of biological processes that has a vital role in personalised medicine.Availability: Source code and data used for producing the presented results are available at: https://gitlab.ics.muni.cz/bias/intomics.
VHL mutations predict survival of patients with renal cell carcinoma in response to the therapy of immune checkpoint inhibitors
Authors: Zhang Jun , Zhao Liqin , Wu Junwei , Wu Zhenhua , Qu Qing
Published: February 2022

Purpose: To identify a predictive biomarker of immune checkpoint inhibitor (ICI) therapies for renal cell carcinoma (RCC). Methods: Survival analysis of mutations in a panel of 468 cancer-related genes in a cohort of 151 RCC patients who underwent the ICI treatment using Cox regression model univariate or multivariate analysis in publicly available datasets. Results: We found that VHL mutations were the only promising independent predictor for overall survival (OS) (HR=0.44, 95% CI=0.25-0.77 and P=0.004). More specifically, compared with 26 months of survival in the wildtype patients, metastatic RCC patients carrying truncated VHL mutations had a significantly longer survival time of nearly 70 months (HR=0.45, 95% CI=0.25-0.82 and P=0.008) in the presence of the ICI therapy. This survival benefit was also observed in another cohort of 35 patients with clear cell RCC from Dana-Farber Cancer Institute (DFCI): compared with 29 months in the wildtype patients, patients with VHL truncated mutations also had a longer median OS of 33 months (HR=0.59, 95% CI=0.24-1.44 and P=0.243). These observed survival benefits were independent of VHL expression and tumor infiltration immune cells in The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA KIRC). Conclusion: VHL mutational inactivation may have an effect on the RCC response to ICI therapy, likely by the upregulation of PD-L1 via attenuating degradation of HIF-1α. To our knowledge, this is the first report of VHL mutations as an independent predictive biomarker for the ICI therapy in RCC, which, once validated by larger clinical trials, may help improve clinical decision-making in individualized treatment of RCC patients.
An active zone state switch concentrates and immobilizes voltage-gated Ca2+ channels to promote long-term plasticity
Authors: Ghelani Tina , Escher Marc , Thomas Ulrich , Esch Klara , Lützkendorf Janine , Depner Harald , Maglione Marta , Parutto Pierre , Gratz Scott , Ryglewski Stefanie , Walter Alexander , Holcman David , O'Connor-Giles Kate , Heine Martin , Sigrist Stephan
Published: February 2022

A molecularly diverse spectrum of plasticity mechanisms orchestrates brain information processing and storage via positive (“Hebbian”) and negative (“homeostatic”) feedbacks, which, however, mechanistically converge and functionally interact in vivo. The presynaptic scaffold proteins that orchestrate active zone (AZ) function undergo plastic remodeling to regulate release potentiation. Here, voltage-gated Ca2+ channel function and their exact AZ nanoscale distribution steer release, although how they are involved in AZ remodeling remains unknown. We here establish intravital, dynamic, single-molecule imaging of endogenously tagged Ca2+ channel Cacophony (Cac) at Drosophila AZs triggered towards homeostatic potentiation. At potentiating AZs, Cac channel numbers increased, and their mobility decreased, while their overall distribution compacted. Mechanistically, RIM-1 and RimBP proteins and their conserved bindings sites, within the Cac channel’s C-terminus, were dispensable for Cac immobilization and compaction. Conversely, the absence of ELKS-family homolog Bruchpilot precluded Cac immobilization and compaction. We show that AZs can undergo a state switch, likely via the ELKS scaffold to concentrate and immobilize Ca2+ channels and thus boost release.
The Characteristics of Laboratory Parameters and Magnetic Resonance Imaging in Different Juvenile Idiopathic Arthritis Subtypes
Authors: Xia Wei , Zhang Yao , Liu Chanyuan , Guo Yu , He Yonglong , Peng Xuehua , Shao Jianbo , Ran Jun
Published: February 2022

Objectives: To explore the characteristics of laboratory parameters, magnetic resonance imaging (MRI) and their relationship in different juvenile idiopathic arthritis (JIA) subtypes. Methods: One hundred and sixty-five patients with JIA identified by diagnostic criteria were involved in the study. Clinical inflammatory biomarkers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), C3, C4, and anti-nucleosome antibodies (ANA) was retrospectively reviewed. Semi-quantitative MRI score was calculated from symptomatic or suspected arthritis for each subject.Results: The median age of onset, median disease duration, ESR, CRP, PLT, IL-6, IL-10, C3, and C4 values were statistically significantly different among different JIA subtypes. The accumulative score of synovitis for different subtype JIA patients has a significant difference (P <0.001). A significant positive relationship between ESR, CRP, RF and C3 values with synovitis score for JIA patients (r= 0.234 and P =0.003, r=0.251 and P =0.001, r=0.208 and P =0.007, r=0.241 and P =0.002 respectively), and a negative relationship between gender and onset age with total synovitis score (r=-0.176 P =0.014 and r=0.-194 P =0.013 respectively) was found by the spearman correlation analyses. Young age at onset, elevated CRP and C3, the long duration of disease were risk factors for synovitis (P＜0.05).Conclusion: Although several risk factors were found for synovitis, the laboratory parameters could not fully explain the severity on MRI, timely baseline and follow-up MRI was still necessary for observing the involvement of symptomatic joints, synovitis especially.
m6A-related lncRNAs Are Potential Biomarkers for Predicting the Prognosis of PAAD Patients
Authors: Chen Yiyang , Zhou Wanbang , Gong Yiju , Liu Jikui , Ou Xi
Published: February 2022

Background: Pancreatic cancer is a common malignant tumor of the digestive system, with insidious onset, difficult early diagnosis, easy metastasis and poor prognosis. N6-methyladenosine and long noncoding RNA play important roles in the prognostic value and immunotherapy response of PAAD. Therefore, it is crucial to recognize m6A-related lncRNAs in PAAD patients.Methods: in this study, m6A-related LncRNAs were obtained by co-expression analysis. Univariate, least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed to construct m6A-related LncRNA prognostic models. Kaplan-Meier analysis, principal component analysis, feature-rich annotation, and nomogram were used to analyze the accuracy of risk models. Finally, potential drugs targeting this model are also discussed. Results: A prognostic model based on m6A-related LncRNA was constructed, potential drugs targeting this m6A-related LncRNA feature were discovered, and the relationship with immunotherapy response was studied. Finally, a nomogram was established to predict survival in PAAD patients.Conclusions: this m6A-based LncRNA risk prognostic model may be promising for clinical prediction of prognosis and immunotherapy response in PAAD patients.
Effect of Geometric Design and Materials on Section Properties of Additively Manufactured Lattice Elements
Authors: Almalki Abduladheem , Downing David , Lozanovski Bill , Tino Rance , Alghamdi Ahmad , Qian Ma , Brandt Milan , Leary Martin
Published: February 2022

Additive Manufacturing (AM) technologies such as Laser-Based Powder Bed Fusion (LB-PBF) enables fabrication of complex lattice structures. However, LB-PBF processes inherently induce dimensional variation between idealised and as-manufactured specimens. This research proposes and implements a method to characterise the structurally relevant geometric properties of as-manufactured strut elements; as demonstrated to characterise the effect of LB-PBF material (aluminium alloy and titanium) and geometric design parameters (polygon order, effective diameter and inclination angle) on the stiffness and strength of as-manufactured strut elements. Micro-computed tomography is applied to algorithmically characterise the as-manufactured variation and identify a threshold below which additional geometric resolution does not result in increased part quality. This methodology provides an algorithmic and robust Design for AM (DFAM) tool to characterise the effect of manufacturing and design parameters on the functional response of AM strut elements, as is required for certification and optimisation.