bluuebunny/crossref_metadata_2025 huggingface dataset:
Geomechanical Template for Distributed Acoustic Sensing Strain Patterns during Hydraulic Fracturing
Authors: Tan Yunhui , Wang Shugang , Rijken Margaretha C. M. , Hughes Kelly , Ning Ivan Lim Chen , Zhang Zhishuai , Fang Zijun
Published: January 2021

Recently more distributed acoustic sensing (DAS) data have been collected during hydraulic fracturing in shale. Low-frequency DAS signals show patterns that are intuitively consistent with the understanding of the strain field around hydraulic fractures. This study uses a fracture simulator combined with a finite element solver to further understand the various patterns of the strain field caused by hydraulic fracturing. The results can serve as a “type-curve” template for the further interpretation of cross-well strain field plots.

Incorporating detailed pump schedule and fracturing fluid/proppant properties, we use a hydraulic fracture simulator to generate fracture geometries, which are then passed to a finite element solver as boundary conditions for elastic-static calculation of the strain field. Because the finite element calculated strain is a tensor, it needs to be projected along the monitoring well trajectory to be comparable with the DAS strain, which is uniaxial. Moreover, the calculated strain field is transformed into a time domain using constant fracture propagation velocity. Strain rate is further derived from the simulated strain field using differentiation along the fracture propagation direction.

Scenarios including a single planar hydraulic fracture, a single fracture with a discrete fracture network (DFN), and multiple planar hydraulic fractures in both vertical and horizontal directions were studied. The scenarios can be differentiated in the strain patterns on the basis of the finite element simulation results. In general, there is a tensile heart-shaped zone in front of the propagating fracture tip shown along the horizontal strain direction on both strain and strain rate plots. On the sides, there are compressional zones parallel to the fracture. The strain field projects beyond the depth where the hydraulic fracture is present. Patterns from strain rate can be used to distinguish whether the fracture is intersecting the fiber. Along the vertical direction, the transition zone depicts the upper boundary of the fracture. A complex fracture network with DFN shows a much more complex pattern compared with a single planar fracture. Multiple planar fractures show polarity reversals in horizontal fiber because of interactions between fractures. Data from the Hydraulic Fracturing Test Site 2 (HFTS2) experiment were used to validate the simulated results.

The application of the study is to provide a template to better interpret hydraulic fracture characteristics using low-frequency DAS strain-monitoring data. To our understanding, there are no comprehensive templates for engineers to understand the strain signals from cross-well fiber monitoring. The results of this study will guide engineers toward better optimization of well spacing and fracturing design to minimize well interference and improve efficiency.
The FAM3C locus that encodes interleukin-like EMT inducer (ILEI) is frequently co-amplified in MET-amplified cancers and contributes to invasiveness
Authors: Schmidt Ulrike , Heller Gerwin , Timelthaler Gerald , Heffeter Petra , Somodi Zsolt , Schweifer Norbert , Sibilia Maria , Berger Walter , Csiszar Agnes
Published: January 2021

Background Gene amplification of MET, which encodes for the receptor tyrosine kinase c-MET, occurs in a variety of human cancers. High c-MET levels often correlate with poor cancer prognosis. Interleukin-like EMT inducer (ILEI) is also overexpressed in many cancers and is associated with metastasis and poor survival. The gene for ILEI, FAM3C, is located close to MET on chromosome 7q31 in an amplification “hotspot”, but it is unclear whether FAMC3 amplification contributes to elevated ILEI expression in cancer. In this study we have investigated FAMC3 copy number gain in different cancers and its potential connection to MET amplifications.Methods FAMC3 and MET copy numbers were investigated in various cancer samples and 200 cancer cell lines. Copy numbers of the two genes were correlated with mRNA levels, with relapse-free survival in lung cancer patient samples as well as with clinicopathological parameters in primary samples from 49 advanced stage colorectal cancer patients. ILEI knock-down and c-MET inhibition effects on proliferation and invasiveness of five cancer cell lines and growth of xenograft tumors in mice were then investigated. Results FAMC3 was amplified in strict association with MET amplification in several human cancers and cancer cell lines. Increased FAM3C and MET copy numbers were tightly linked and correlated with increased gene expression and poor survival in human lung cancer and with extramural invasion in colorectal carcinoma. Stable ILEI shRNA knock-down did not influence proliferation or sensitivity towards c-MET-inhibitor induced proliferation arrest in cancer cells, but impaired both c-MET-independent and -dependent cancer cell invasion. c-MET inhibition reduced ILEI secretion, and shRNA mediated ILEI knock-down prevented c-MET-signaling induced elevated expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Combination of ILEI knock-down and c-MET-inhibition significantly reduced the invasive outgrowth of NCI-H441 and NCI-H1993 lung tumor xenografts by inhibiting proliferation, MMP expression and E-cadherin membrane localization.Conclusions These novel findings suggest MET amplifications are often in reality MET-FAM3C co-amplifications with tight functional cooperation. Therefore, the clinical relevance of this frequent cancer amplification hotspot, so far dedicated purely to c-MET function, should be re-evaluated to include ILEI as a target in the therapy of c-MET-amplified human carcinomas.
Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration
Authors: Levin Fedor , Ferreira Daniel , Lange Catharina , Dyrba Martin , Westman Eric , Buchert Ralph , Teipel Stefan , Grothe Michel
Published: January 2021

Background

Previous research has described distinct subtypes of Alzheimer’s disease (AD) based on differences in regional patterns of brain atrophy on MRI. We conducted a data-driven exploration of distinct AD neurodegeneration subtypes using FDG-PET as a sensitive molecular imaging marker of neurodegenerative processes.

Methods

Hierarchical clustering of voxel-wise FDG-PET data from 177 amyloid-positive patients with AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was used to identify distinct hypometabolic subtypes of AD, which were then further characterized with respect to clinical and biomarker characteristics. We then classified FDG-PET scans of 217 amyloid-positive patients with mild cognitive impairment (‘prodromal AD’) according to the identified subtypes and studied their domain-specific cognitive trajectories and progression to dementia over a follow-up interval of up to 72 months.

Results

Three main hypometabolic subtypes were identified: (i) “typical” (48.6%), showing a classic posterior temporo-parietal hypometabolic pattern, (ii) “limbic-predominant” (44.6%), characterized by old age and a memory-predominant cognitive profile, and (iii) a relatively rare “cortical-predominant” subtype (6.8%) characterized by younger age and more severe executive dysfunction. Subtypes classified in the prodromal AD sample demonstrated similar subtype characteristics as in the AD dementia sample and further showed differential courses of cognitive decline.

Conclusions

These findings complement recent research efforts on MRI-based identification of distinct AD atrophy subtypes and may provide a potentially more sensitive molecular imaging tool for early detection and characterization of AD-related neurodegeneration variants at prodromal disease stages.
Human Drug Efflux Transporter ABCC5 Confers Acquired Resistance to Pemetrexed in Breast Cancer
Authors: Chen Jihui , Wang Zhipeng , Gao Shouhong , Wu Kejin , Bai Fang , Zhang Qiqiang , Wang Hongyu , Ye Qin , Xu Fengjing , Sun Hong , Lu Yunshu , Liu Yan
Published: January 2021

AimPemetrexed, a new generation antifolate drug, is approved for the treatment for locally advanced or metastatic breast cancer, but factors affecting the efficacy and resistance of it have yet to be fully explicit. ATP-binding cassette (ABC) transporters have been reported as prognostic and adverse effects predictors of many xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and may contribute to treatment regimen optimization for breast cancer.MethodsFirstly, the expression of ABC transporters family members was measured in cell lines, thereafter examined the potential role of ABC transporter in conferring resistance to pemetrexed in primary cancer cell lines isolated from 34 breast cancer patients, and then the role of ABCC5 in mediating transport of pemetrexed and apoptosis pathway in MCF-7 cell line was assessed. Finally, the functions of ABCC5 on therapeutic effect of pemetrexed was evaluated in breast cancer bearing mice.ResultsThe expressions of ABCC2, ABCC4, ABCC5 and ABCG2 were significantly increased in pan-resistance cell line, and the ABCC5, the most obvious one, was 5.21 times higher than that of the control group. The expression of ABCC5 was inversely correlated with sensitivity (IC50) of pemetrexed (r = 0.741; p<0.001) in breast cancer cells from 34 patients. Furthermore, we found that the expression of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cell line, and the IC50 were 0.06 μg/ml and 0.20 μg/ml in ABCC5 knock-down and over-expression cells, respectively. In in vivo study, we found ABCC5 affected the sensitivity of pemetrexed in breast cancer bearing mice, and the tumor volume was much larger in ABCC5 over-expression group than that in control group (2.7 folds vs 1.3 folds).ConclusionsOur results indicated ABCC5 expression was associated with pemetrexed resistance in vitro and in vivo, and may be a biomarker for regimen optimization of pemetrexed in breast cancer treatment.
The Investigational Clinical Center: a clinical-supportive and patient-centered trial unit model. Ten years of experience through normal and pandemic times of a large pediatric Trial Center in Italy.
Authors: Pontrelli Giuseppe , Ciabattini Marco , De Crescenzo Franco , Biondi Isabella , Cocchiola Rossana , Copponi Giorgia , Frillici Claudia , Molinari Francesca , Rocchi Francesca , Simonetti Alessandra , Rossi Paolo , Livadiotti Susanna
Published: January 2021

Evidence-based medicine relies on appropriately designed, conducted and reported clinical trials (CTs) to provide the best proofs of efficacy and safety for pharmacological and non-pharmacological treatments. Modern clinical research features high complexity and requires a high workload for the management of trials-related activities, often hampering physicians’ participation to clinical trials. Dealing with children in clinical research adds complexity: rare diseases, parents or legal guardian reluctance to engage and recruitment difficulties are major reasons of pediatric trials failure. However, because in pediatrics many treatments are prescribed off-label or are lacking, well-designed clinical trials are particularly needed. Clinical Trial Units (CTUs) are indeed an important asset in the implementation of clinical trials, but their support to investigators is limited to administrative and non-clinical tasks. In this paper we present the model of the Investigational Clinical Center (ICC) of the Bambino Gesù Children’s Hospital in Rome. The ICC includes clinicians supporting the Principal Investigators for clinical management of enrolled patients in compliance of Good Clinical Practice, the legal framework of Clinical Trials. Furthermore, we present ten years’ experience in pediatric clinical trials and how it has been affected in 2020 by the COVID-19 pandemic. The activity of the ICC has been evaluated according to specific metrics of performance. The ICC model offers a complete support, helping investigators, patients and their families to overcome majority of barriers linked to clinical research, even in time of pandemic. We propose this organization as an innovative model for total-supportive and patient-centered clinical trial implementation.
Impact of an acute Care Surgery Model on the Management of acute Appendicitis in South Korea: A Retrospective Cohort Study
Authors: Yi Gun-Hee , Lee Hak-Jae , Lee Seul , Yoon Jong-Hee , Hong Suk-Kyung
Published: January 2021

Background The acute care surgery (ACS) system is a new model for the prompt management of diseases that require rapid treatment in patients with acute abdomen. This study compared the outcomes and characteristics of the ACS system and traditional on-call system (TROS) for acute appendicitis in South Korea. Methods This single-center, retrospective study included all patients (aged ≥18 years) who underwent surgery for acute appendicitis in 2016 and 2018. The TROS and ACS system were used for the 2016 and 2018 groups, respectively. We retrospectively obtained data on each patient from the electrical medical records. The independent samples t-test and Mann-Whitney U-test were used for continuous and non-normally distributed data, respectively.Results In total, 126 patients were included. The time taken to get from the emergency room admission to the operating room, operation times, and postoperative complication rates were similar between both groups. However, the length of the hospital stay was shorter in the ACS group than in the TROS group (4.3±3.2 days vs. 7.2±9.6 days, p=0.039).Conclusions Since the introduction of the ACS system, the length of hospital stay for surgical patients has decreased. This may be due to the application of an integrated medical procedure, such as a new clinical pathway, rather than differences in the surgical techniques.Trial registration: Retrospectively registered.
A climate investment trap in developing economies
Authors: Ameli Nadia , Dessens Olivier , Winning Matthew , Cronin Jennifer , Chenet Hugues , Drummond Paul , Calzadilla Alvaro , Anandarajah Gabrial , Grubb Michael
Published: January 2021

Finance is vital for the green energy transition, but the access to low cost finance is uneven as the cost of capital differs substantially between regions. This study shows how modelled decarbonisation pathways of developing economies are disproportionately impacted by assumptions around their cost of capital (WACC). For example, representing regionally specific WACC values indicates 35% lower green electricity production in Africa for a cost-optimal 2°C pathway. Moreover, results show that early convergence of WACC values for green and brown technologies in 2050 would allow Africa to reach net-zero emissions approximately 10 years earlier than when convergence is not considered. A “climate investment trap” arises for developing economies when climate-related investments remain chronically insufficient. Elements of sustainable finance frameworks currently present barriers to these finance flows and radical changes are needed so that capital is better allocated to the regions that most need it.
Towards health equity for people experiencing chronic pain and social marginalization
Authors: Wallace Bruce , Varcoe Colleen , Holmes Cindy , Moosa-Mitha Mehmoona , Moor Gregg , Hudspith Maria , Craig Kenneth D
Published: January 2021

Objective: For people who experience social inequities and structural violence, pain and related care are inexorably linked to experiences of injustice and stigma. The purpose of this study was to examine in greater depth the experiences of pain and discrimination and stigma across diverse marginalized communities in order to recommend equity-oriented healthcare approaches. Methods: This community-based qualitative study reports on four focus groups that included 36 people living with pain. All participants identified with one of three groups known to experience high levels of inequities and structural violence including an Indigenous group, a LGBTQ2S group, and two newcomer and refugee groups. Results: Pain was entangled with and shaped by: social locations and identities, experiences of violence, trauma and related mental health issues, experiences of discrimination, stigma and dismissal, experiences of inadequate and ineffective health care, and the impacts of these intersecting experiences. Conclusions: Equity-oriented responses to chronic pain would recognize pain not only as a biomedical issue but as a social justice issue. The EQUIP Framework is an approach to integrating trauma- and violence-informed care; culturally-safe care; and harm reduction in health care that may hold promise for being tailored to people experiencing pain and social marginalization.
Treadmill running regulates adult neurogenesis, spatial and non-spatial learning by ErbB4 signaling
Authors: Yi Yandong , Song Yuanlong , Liu Bo , Lu Yisheng
Published: January 2021

Recent studies have shown exercise is effective for adult hippocampus neurogenesis and memory. However, the molecular mechanism of exercise is unclear. In this study, AG1478, an ErbB4 inhibitor, was used to explore the involvement of ErbB4 receptors. Four weeks post-running, cognitive impairment was analyzed using T-maze, Morris water maze (MWM) and contextual fear discrimination learning tests, followed by histological assessment of the proliferation and survival of hippocampal neurons using Ki67, NeuN and BrdU immunostaining respectively. Expression of total and phosphate ErbB4 protein level was evaluated by Western blotting. The results showed that AG1478 significantly impaired the performances in T-maze and MWM (spatial learning and memory), contextual fear conditioning and discrimination learning paradigm (non-spatial working and reference memory), enhanced neurogenesis loss, downregulated the expression of p-ErbB4 and total ErbB4 protein, which could be reversed by running. Taken together, our study suggested that running ameliorates cognitive impairment and neurogenesis via ErbB4 signaling.
Airway Pseudomonas aeruginosa Density in Mechanically Ventilated Patients: Clinical Impact and Relation to Therapeutic Efficacy of Antibiotics
Authors: Migiyama Yohei , Sakata Shinya , Iyama Shinji , Tokunaga Kentaro , Saruwatari Koichi , Tomita Yusuke , Saeki Sho , Okamoto Shinichiro , Ichiyasu Hidenori , Sakagami Takuro
Published: January 2021

Background: The bacterial density of Pseudomonas aeruginosa (PA) is closely related to its pathogenicity. We evaluated the effect of airway PA density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics.Methods: We retrospectively analyzed data of intensive care unit (ICU) mechanically ventilated patients with PA isolated from endotracheal aspirates. Patients were divided into three groups according to the peak PA density during ICU stay: low-PA (≤ 104 colony-forming units [cfu]/mL), moderate-PA (105‒106 cfu/mL), and high-PA (≥ 107 cfu/mL) groups. The relationship between PA density and weaning from mechanical ventilation, risk factors for high-PA isolation, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses.Results: A total of 461 patients were enrolled. Patients with high-PA had higher inflammation marker levels and developed more severe respiratory infections. High PA was independently associated with fewer ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high PA were prolonged mechanical ventilation (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizers was associated with lower risks of high PA (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analyses revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high-PA group.Conclusions: High PA significantly affected the clinical course of mechanically ventilated patients and could be a good therapeutic indicator for ventilator-associated tracheobronchitis treatment.
ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma
Authors: Zhang Mengzhao , Wang Lu , Yue Yangyang , Zhang Lu , Liu Tianjie , Jing Minxuan , Liang Xiao , Ma Minghai , Xu Shan , Wang Ke , Wang Xinyang , Fan Jinhai
Published: January 2021

Background: Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells.Methods: The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model.Results: Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process.Conclusions: Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.
First Evidence for Nicotiana (Tobacco) and its Human Use in Pleistocene North America
Authors: Duke Daron , Wohlgemuth Eric , Adams Karen , Armstrong-Ingram Angela , Rice Sarah , Young D.
Published: January 2021

Current studies on cultigens emphasize the protracted and intimate human interactions with wild species that defined paths to domestication and, for certain plants, profoundly impacted humanity1,2. Tobacco (Nicotiana) is one such plant. Tobacco arguably has had more impact on global patterns in history than any other psychoactive substance, but how deep its cultural ties trace back is widely debated. Adding to the puzzle is whether the distribution of tobacco in North America occurred naturally or if humans themselves were responsible for its expansion across the continent3. Archaeological excavations at the Wishbone site, directed at the hearth-side activities of the early inhabitants of North America’s desert west, have uncovered evidence for tobacco approximately 12,300 years ago, 9,000 years earlier than previously documented4. Here we detail the preservation context of the site, discuss its cultural affiliation, and consider the ways that the tobacco may have been used. Researchers have long suspected that human use extends earlier in time than can been readily demonstrated by such fragile remains3–7, so the finding reinvigorates research on the driving cultural forces behind tobacco’s use, cultivation, and subsequent domestication. This has implications for our understanding of deep-time human use of plant intoxicants, the intersection of non-food plant domestication with that of food crops, and the trajectory of selective, potentially independent, interactions with tobacco from a broad cultural milieu in ancient North America to a place of worldwide cross-cultural significance.
Association Between Social Media and Psychological Effects Among Adolescents: A School Based Cross-Sectional Study in Kathmandu City of Nepal
Authors: Paudel Ashok , Chhetri Muni , Baidya Prinisha
Published: January 2021

Background: Social media are comprised of websites and software applications that enable users to create and share content or to participate in social networking. Inappropriate use of social media may lead to negative psychological effects. This study aimed to assess the psychological effects of social media among adolescent students of Grade 9 and 10 in Kathmandu city of Nepal. Methods: A Cross-sectional school-based study done among randomly sampled adolescent students (10-19 yrs) of Grade 9 and 10. Total 318 sample size derived using the formula: n=z²pq/e2. Social Media Addiction Scale Student Form and Short Mood and Feelings Questionnaire were the self-administered data collection tools. The purpose of the study was explained to respondents. Ethical approval was obtained through the Ethical Review Board of Nepal Health Research Council. Data were analyzed on Scientific Package for Social Science version-20. Results: About sixty-two percent of the adolescents had their cell phones and 88.1 percent had internet facilities in their houses. Forty-six percent of adolescents were addicted to social media and 68.2 percent were depressed. Out of depressed adolescents, 64.4 percent of them had social media addiction. The significant association observed between adolescents with their cell phone and social media addiction (p=0.037); social media addiction and depression (p= 0.000). Conclusions: Adolescents with their cell phone is associated with social media addiction and social media addiction is associated with depression, suggesting an urgent need to develop policies and programs to mitigate negative psychological effects of cell phones and social media addiction.
Inferring differential subcellular localisation in comparative spatial proteomics using BANDLE
Authors: Crook Oliver , Davies Colin , Gatto Laurent , Kirk Paul , Lilley Kathryn
Published: January 2021

The steady-state localisation of proteins provides vital insight into their function. These localisations are context specific with proteins translocating between different sub-cellular niches upon perturbation of the subcellular environment. Differential localisation provides a step towards mechanistic insight of subcellular protein dynamics. Aberrant localisation has been implicated in a number of pathologies, thus differential localisation may help characterise disease states and facilitate rational drug discovery by suggesting novel targets. High-accuracy high-throughput mass spectrometry-based methods now exist to map the steady-state localisation and re-localisation of proteins. Here, we propose a principled Bayesian approach, BANDLE, that uses these data to compute the probability that a protein differentially localises upon cellular perturbation, as well quantifying the uncertainty in these estimates. Furthermore, BANDLE allows information to be shared across spatial proteomics datasets to improve statistical power. Extensive simulation studies demonstrate that BANDLE reduces the number of both type I and type II errors compared to existing approaches. Application of BANDLE to datasets studying EGF stimulation and AP-4 dependent localisation recovers well studied translocations, using only two-thirds of the provided data. Moreover, we implicate TMEM199 with AP-4 dependent localisation. In an application to cytomegalovirus infection, we obtain novel insights into the rewiring of the host proteome. Integration of high-throughput transcriptomic and proteomic data, along with degradation assays, acetylation experiments and a cytomegalovirus interactome allows us to provide the functional context of these data.
Super-elasticity at 4K of Covalently Crosslinked Polyimide Aerogels with Ultrahigh Negative Poisson’s Ratio
Authors: Cheng Yang , Zhang Xiang , Qin Yixiu , Dong Pei , Yao Wei , Matz John , Ajayan Pulickel , Shen Jianfeng , Ye Mingxin
Published: January 2021

The deep cryogenic temperatures encountered in aerospace present significant challenges for the performance of elastic materials in spacecrafts and related apparatus. Reported elastic carbon or ceramic aerogels overcome the low-temperature brittleness in conventional elastic polymers. However, complicated fabrication process and high costs greatly limited their applications. In this work, super-elasticity at deep cryogenic temperature of covalently crosslinked polyimide (PI) aerogels is achieved based on scalable and low-cost directional dimethyl sulfoxide crystals assisted freeze-gelling and freeze-drying strategy. The covalently crosslinked chemical structure, cellular architecture, negative Poisson’s ratio (-0.2), extremely low volume shrinkage (3.1%) and ultralow density (6.1 mg/cm3) endow the PI aerogels with an elastic compressive strain up to 99% even in liquid helium (4K), almost zero loss of resilience after dramatic thermal shocks (∆T = 569 K), and fatigue resistance over 5000 times compressive cycles. This work provides a new pathway for constructing polymer-based materials with super-elasticity at deep cryogenic temperature, demonstrating much promise for extensive applications in ongoing and near-future aerospace exploration.
Influence of Old Age on Risk of Lymph Node Metastasis and Survival in Patients With T1 Colorectal Cancer: A Population-Based Analysis
Authors: Ye Hua , Zheng Bin , Zheng Qi , Chen Ping
Published: January 2021

Background We aimed at determining the influence of old age on lymph node metastasis (LNM) and prognosis in T1 colorectal cancer (CRC). Methods We collected data from eligible patients in Surveillance, Epidemiology, and End Results database between 2004 and 2015. Independent predictors of LNM were identified by the logistic regression analysis. Cox regression analysis, propensity score-matched analysis and competing risks analysis were used to analyze the associations between old age and lymph node (LN) status, and to validate the prognostic value of old age on cancer-specific survival (CSS).Results In total, 10092 patients were identified. Among them, 6423 patients (63.6%) had greater than or equal to 12 examined lymph nodes (LNs) (LNE ³12), and 5777 patients (57.7%) were of 65 years or older. The observed rate of LNM was 14.9 % (960 out of 6423). Logistic regression models demonstrated that tumor size ³3cm (odds ratio, OR = 1.316, P = 0.038), poorly differentiated (OR = 3.716, P <0.001), older age (OR = 0.633 for age 65–79 years, OR= 0.477 for age over 80 years, both P < 0.001), and negative CEA level (OR = 0.71, P =0.007) were independent prognostic factors. Cox regression analysis demonstrated CSS was not significantly different between elderly patients undergoing radical resection with LNE³12 and those with LNE <12 (HR= 0.865, P = 0.153), which were firmly validated after propensity score-matched analysis by a competing risks model.Conclusions We found that tumor size<3cm, well/moderately differentiated, negative CEA level and adenocarcinoma in elderly patients with T1 colorectal cancer who were suitable for Local excision.
Conjugate Buoyant Convective Transport of Different Nanofluids in An Enclosed Annular Geometry
Authors: Sankar M. , Reddy N. Keerthi , Do Younghae
Published: January 2021

A vertical annular configuration with differently heated cylindrical surfaces and horizontal adiabatic boundaries is extensively studied due to many industrial applications. In this paper, we investigate the effects of conjugate buoyant heat transport within water based nanofluid with different nanoparticles such as alumina, titanium oxide or copper, which is contained in the gap of the enclosed annulus. The enclosed annulus is constituted by a thick inner cylinder with a constant high temperature, an exterior boundary with a constant low temperature and thermally insulated upper and lower surfaces. By investigating heat transport for broad spectrum of Rayleigh number, solid wall thickness, thermal conductivity ratio and nanoparticle volume fraction, we found that the influence of wall thickness on thermal dissipation rate along wall and interface greatly depend on conductivity ratio and vice-versa. In particular, we uncover that the choice of nanoparticle in a nanofluid and its concentration are key factors in enhancing the thermal transport along the interface. Specially, copper based nanofluids produces higher heat transport among other nanoparticles, and increasing nanoparticle concentration leads to enhanced thermal dissipation along interface. Our results are applicable to choose nanofluids along with other critical parameters for the desired heat transport.
Survival after Surgery among Patients with Cholangiocarcinoma in Northeast Thailand According to Anatomical and Morphological Classification
Authors: Thawarungruang Chaiwat , Khuntikeo Narong , Chamadol Nittaya , Laopaiboon Vallop , Thuanman Jaruwan , Thinkhamrop Kavin , Kelly Matthew , Thinkhamrop Bandit
Published: January 2021

Background: Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods: This study included CCA patients who underwent curative surgery with a pathological diagnosis from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results: Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The mortality rate was 3.3 per 100 patients per month (95% CI: 3.0-3.6), with median survival time of 17.8 months (95% CI: 15.4-20.2), and 5-year survival rate of 24.6% (95% CI: 20.7­28.6). The longest median survival time was 21.8 months (95% CI: 16.3-27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8-46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9-63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4-58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01-2.09; P = 0.013) compared to ICCA+ID patients. Conclusions: Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.
β-Conglycinin Regulates Intestinal Immunity through the CIITA-mediated MHC II-PI3K/Akt/mTOR Pathway in Hybrid Grouper: The Ameliorative Effects of Sodium Butyrate (NaB)
Authors: Yin Bin , Liu Hongyu , Tan Beiping , Dong Xiaohui , Chi Shuyan , Yang Qihui , Zhang Shuang
Published: January 2021

We investigated the effects of low and high doses of 7S and the ameliorative effects of NaB (based on high-dose 7S) on the growth performance, serum immunity, distal histopathology, and CIITA-mediated MHC II-PI3K/Akt/mTOR pathway in hybrid groupers. The results revealed that the specific growth rate of groupers significantly increased, decreased, and increased in the low-level 7S (bL), high-level 7S (bH) high-level 7S plus NaB (bH-NaB) groups, respectively. The feed coefficient ratio was significantly increased in the bH and bH-NaB groups, whereas serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH group. The intestinal diameter/plica height ratio was significantly increased in the bH group. Furthermore, there were increases in nitric oxide, nitric oxide synthase (NOS), and peroxynitrite anion (ONOO−) in the bH group, and decreases in NOS and ONOO− in the bH-NaB group. The mRNA levels in distal intestine of TSC1, mTOR C2, CIITA, and CREB1 were significantly upregulated in all three treatment groups, whereas those of IKKα, Rheb, mTOR C1, mLST8, EIF4B, NFY, GILT, and AEP were upregulated and downregulated in the bH and bH-NaB groups, respectively. These indicate 7S has a regulatory effect on serum immunity and affect distal intestinal development by modulating hindgut injury-related parameters. Within the distal intestinal tract, 7S can induce intestinal inflammation by activating the CIITA-mediated MHC II-PI3K/Akt/mTOR pathway, which eventually manifests as a reduction in growth performance. Supplementing feed with NaB represents an effective approach for enhancing serum immunity, and also protects the intestines from damage caused by high-dose 7S.
Seminal Plasma piRNA Array Analysis Identifies Possible Biomarker piRNAs for the Diagnosis of Asthenozoospermia
Authors: he ling , wu Xing , wu rong , guo ping , sun Wan , he wen , chen he
Published: January 2021

Asthenozoospermia (AZS) is characterized by reduced sperm motility, and its pathogenesis remains poorly understood. Piwi-interacting RNAs (piRNAs) have been recognized to play important roles in spermatogenesis. However, little is known about the correlation of piRNAs with AZS. In this study, small RNA sequencing was performed on samples from AZS patients and fertile controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the small RNA-seq results. Bioinformatics analyses were performed to predict the functions of differentially expressed piRNAs. Logistic regression models were constructed, and receiver operating characteristic curve (ROC) analysis was used to evaluate their diagnostic performance. A total of 114 upregulated and 169 downregulated piRNAs were detected in AZS patients. GO and KEGG analyses showed that the differentially expressed piRNAs were mainly associated with transcription, signal transduction, cell differentiation, metal ion binding and focal adhesion. These results were verified by qRT-PCR of 8 selected piRNAs. Among the differentially expressed piRNAs tested, piR-hsa-32694, piR-hsa-26591, piR-hsa-18725, piR-hsa-18586 and piR-hsa-2912 produced qRT-PCR results consistent with the sequencing results in AZS compared with controls in the first cohort, whereas the other three genes did not show significant differences in expression. piR-hsa-32694, piR-hsa-26591, piR-hsa-18725, and piR-hsa-18586 were significantly upregulated in AZS. The diagnostic power of the four piRNAs was further analysed using ROC analysis; piR-hsa-26591 exhibited an area under the ROC curve (AUC) of 0.913 (95% CI: 0.795-0.994). Logistic regression modelling and subsequent ROC analysis indicated that the combination of the 4 piRNAs reached good diagnostic efficacy (AUC: 0.935).
TGFB-Induced Factor Homeobox 1 (TGIF) Expression in Breast Cancer
Authors: Stürken Christine , Möbus Volker , Milde-Langosch Karin , Schmatloch Sabine , Fasching Peter , Rüschoff Josef , Stickeler Elmar , Henke Rolf-Peter , Denkert Carsten , Hanker Lars , Schem Christian , Vladimirova Valentina , Karn Thomas , Nekljudova Valentina , Köhne Claus-Henning , Marmé Frederik , Schumacher Udo , Loibl Sibylle , Müller Volkmar
Published: January 2021

Background: Breast cancer (BC) is the most frequent female cancer its which preferentially metastasizes to bone. Mechanisms of bone tropism are poorly understood, however, the transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism and thus of potential interest.Methods: TGIF expression was analyzed by immunohistochemistry in 1197 formalin-fixed, paraffin-embedded tissue from BC patients treated in the GAIN study with two adjuvant dose-dense schedules of chemotherapy with or without bisphosphonate ibandronate. TGIF expression was categorized into negative/low and moderate/strong staining.Results: In 1197 samples, we found associations of higher TGIF protein expression with smaller tumor size (p = 0.015), well differentiated phenotype (p < 0.001) and estrogen receptor (ER)-positive BC (p < 0.001). Patients with higher TGIF expression levels showed a significantly better disease-free (log-rank p 0.019) and overall survival (log-rank p = 0.018), but no association with time to bone metastasis as first site of relapse. Stratified univariate analysis in molecular subgroups emphasized that elevated TGIF expression was prognostic for both DFS and OS in ER-positive BC patients (DFS: log-rank p = 0.009; OS: log-rank p = 0.008) and in the HER2-negative subgroup (DFS: log-rank p = 0.004; OS: log-rank p = 0.002).Conclusions: Our findings suggest that a loss of TGIF expression is associated with BC progression, especially in luminal carcinomas.Trial registration: This clinical trial has been registered with ClinicalTrials.gov; registration number: NCT00196872.
Determination of Dy Substitution Site in Nd2-xDyxFe14B by HAADF-STEM and Illustration of Magnetic Anisotropy of “g” and “f” Sites, Before and After Substitution
Authors: Kang Young , Haider Syed , Kang Min-Chul , Hong Jisang , Yang Cheol-Woong , Kim Dongsoo
Published: January 2021

Nd2Fe14B and Nd2 − xDyxFe14B (x = 0.25,0.50) particles were prepared by the modified co-precipitation followed by reduction-diffusion process. Bright field scanning transmission electron microscope (BF-STEM) image revealed the formation of Nd-Fe-B trigonal prisms in [-101] viewing zone axis, confirming the formation of Nd2Fe14B/Nd2 − xDyxFe14B. Accurate site for the Dy substitution in Nd2Fe14B crystal structure was determined as “f” site by using high-angle annular dark field scanning transmission electron microscope (HAADF-STEM). It was found that all the “g” sites are occupied by the Nd, where’s and Dy occupied only the “f” site. Anti-ferromagnetic coupling at “f” site decreased the magnetic moment values for Nd1.75Dy0.25Fe14B (23.48 µB) and Nd1.5Dy0.5Fe14B (21.03 µB) as compared to Nd2Fe14B (25.50 µB). Reduction of magnetic moment increased the squareness ratio, coercivity and energy product. Analysis of magnetic anisotropy at constant magnetic field confirmed that “f” site substitution did not change the patterns of the anisotropy. Furthermore, magnetic moment of Nd2Fe14B, Nd2 − xDyxFe14B, Nd (“f” site), Nd (“g” site) and Dy (“f” site) was recorded for all angles between 0-180o.
Parameter Study of the High Temperature MOCVD Numerical Model for AlN Growth Using Orthogonal Test Design
Authors: an jiadai , dai xianying , feng lansheng , zheng jieming
Published: January 2021

We investigated the process parameters of the high temperature MOCVD (HT-MOCVD) numerical model for the AlN growth based on CFD simulation using orthogonal test design. It is believed that high temperature growth condition is favorable for improving efficiency and crystallization quality for AlN film, while the flow field in the HT-MOCVD reactor is closely related to the process parameters, which will affect the uniformity of the film. An independently developed conceptual HT-MOCVD reactor was established for the AlN growth to carry out the CFD simulation. To evaluate the role of the parameters systematically and efficiently on the growth uniformity, the process parameters based on CFD simulation were analyzed using orthogonal test design. The advantages of the range, matrix and variance methods were considered and the results were analyzed comprehensively and the optimal process parameters were obtained as follows, susceptor rotational speed 400 rpm, operating pressure 40 Torr, gas flow rate 50 slm, substrate temperature 1550 K.
Association Between Smoking Status and Outcomes in ST-Segment Elevation and Non-ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention
Authors: Sia Ching-Hui , Ko Junsuk , Zheng Huili , Ho Andrew , Foo David , Foo Ling-Li , Lim Patrick , Liew Boon , Chai Ping , Yeo Tiong-Cheng , Tan Huay-Cheem , Chua Terrance , Chan Mark , Tan Jack , Bulluck Heerajnarain , Hausenloy Derek
Published: January 2021

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effects of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.
The Value of Alveolar Lavage Fluid mNGS in The Peripheral Pulmonary Among Children
Authors: Qiu Kun-yin , Liao Xiong-yu , Fang Jian-pei , Zhou Dun-hua
Published: January 2021

Objectives The aim of this study was to evaluate the value of alveolar lavage fluid mNGS in the diagnosis of peripheral pulmonary infectious lesions among children. Methods Twenty-eight consecutive pediatric patients suspected of pulmonary infections were retrospectively. Result The detection rate of traditional pathogen method was 17.9%, while the detection rate of mNGS was 71.4% (P < 0.01,). The smoothing curve also showed that, there is a negative linear correlation between WBC and microbial reads (P < 0.05,). Further we found when CRP is less than 60mg/dl, CRP increases with the increase of microbial sequencing reads. With the ROC curves, we demonstrated the different detection methods of alveolar lavage fluid in the diagnosis of peripheral pulmonary infectious lesions.The results showed that mNGS was more sensitive (100%) and specific (90.9%) compared to traditional method (83.3%, 18.2%). The PPV and NPV of mNGS were 100% and 75%. The AUC of mNGS was 95.45%, while the AUC of traditional methods was 50.76%, which was with a significant difference (P < 0.001). The PPV and NPV of traditional pathogen detection were 80% and 21.7%. Conclusions Metagenomic NGS analysis can provided fast and precise pathogen detection and identification among children, and WBC and CRP could be used biomarkers of anti-infective efficacy.