bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
Authors: Au K. S. , Hebert L. , Hillman P. , Baker C. , Brown M. R. , Kim D.-K. , Soldano K. , Garrett M. , Ashley-Koch A. , Lee S. , Gleeson J. , Hixson J. E. , Morrison A. C. , Northrup H. 
Published: February 2021

AbstractMyelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.
Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma
Authors: Wu Chunlei , Hu Quanteng , Ma Dehua 
Published: February 2021

AbstractLung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.
Targeting the DNA replication stress phenotype of KRAS mutant cancer cells
Authors: Al Zubaidi Tara , Gehrisch O. H. Fiete , Genois Marie-Michelle , Liu Qi , Lu Shan , Kung Jong , Xie Yunhe , Schuemann Jan , Lu Hsiao-Ming , Hata Aaron N. , Zou Lee , Borgmann Kerstin , Willers Henning 
Published: February 2021

AbstractMutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.
Urodynamic evaluation of patients with localized prostate cancer before and 4 months after robotic radical prostatectomy
Authors: Lee Dong Sup , Lee Seung-ju 
Published: February 2021

AbstractRadical prostatectomy can alter the anatomy of the urinary bladder. We aimed to evaluate bladder function before and 4 months after radical prostatectomy using the urodynamic test and overactive bladder (OAB) symptom score. Among 70 prospectively enrolled patients, 61 patients completed the study. In the urodynamic test, bladder capacity and compliance did not change, the frequency of involuntary detrusor contraction decreased, the maximum flow rate and bladder outlet obstruction index improved, and the maximum urethral closure pressure (MUCP) deteriorated. Further evaluation of urodynamic parameters according to changes in symptoms was made. Although change in bladder compliance was correlated with changes in OAB symptoms, not the relative change of bladder compliance but the relative change in the MUCP was reliable factor when OAB symptoms were deteriorated. In general, prostatectomy did not deteriorate the condition of the detrusor; rather, change in the MUCP could be responsible for postprostatectomy OAB.
Effects of silicon doping on low-friction and high-hardness diamond-like carbon coating via filtered cathodic vacuum arc deposition
Authors: Kim Jae-Il , Jang Young-Jun , Kim Jisoo , Kim Jongkuk 
Published: February 2021

AbstractIn this study, silicon (Si) was doped on a tetrahedral amorphous carbon (ta-C) coating and the tribological characteristics of the resulting Si-doped diamond-like carbon (DLC; a-C:Si:H) were investigated against a SUJ2 ball. The Si fraction in the coating was varied from 0 to ~ 20 at.% by increasing the trimethylsilane gas flow rate during filtered cathodic vacuum arc deposition. The coefficient of friction (CoF) showed no obvious change when the Si fraction was less than ~ 7 at.%. However, after Si doping, it significantly decreased when the Si fraction was greater than ~ 8 at.%. The running-in period also decreased to less than 1000 cycles after Si doping. The rapid formation of Si-rich debris and transfer layer led to the fabrication of a low-friction tribofilm, which was induced by the tribochemical reaction with moisture under ambient conditions. When the Si fraction was ~ 17 at.%, the lowest CoF of less than 0.05 was obtained. Further Si doping beyond the critical point led to the destruction of the film because of reduced hardness.
Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of breast cancer: a prospective study
Authors: Pasquier David , Bataille Benoit , Le Tinier Florence , Bennadji Raoudha , Langin Hélène , Escande Alexandre , Tresch Emmanuelle , Darloy Franck , Carlier Damien , Crop Frederik , Lartigau Eric 
Published: February 2021

AbstractORCID: 0000–0001-6019–7309. In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). Comparisons with conventional radiotherapy have shown that IMRT is associated with lower frequencies of acute and late-onset AEs. Here, we extended a prospective, observational, single-center study of the safety of IMRT to a second investigating center. Patients scheduled for adjuvant IMRT after partial or total mastectomy were given a dose of 50 Gy (25 fractions of 2 Gy over 5 weeks), with a simultaneous integrated boost in patients having undergone conservative surgery. 300 patients were included in the study, and 288 were analyzed. The median follow-up period was 2.1 years. The 2-year disease-free survival rate [95% CI] was 93.4% [89.2–96.0%]. Most AEs were mild. The most common AEs were skin-related—mainly radiodermatitis [in 266 patients (92.4%)] and hyperpigmentation (in 178 (61.8%)). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Only 4 patients presented with a grade 3 event (radiodermatitis). Smoking (odds ratio) [95% CI] = 2.10 [1.14–3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27–0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001–1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters.Trial registration: ClinicalTrials.gov NCT02281149.
Quality of life of HIV-negative, previously healthy individuals following cryptococcal meningoencephalitis
Authors: Dean Owen , Anjum Seher , Scott Terri , Ham Lillian , Traino Katherine , Wang Jing , Hunsberger Sally , Powers John H. , Marr Kieren A. , Snow Joseph , Williamson Peter R. 
Published: February 2021

AbstractThe morbidity and mortality of cryptococcal meningoencephalitis (CM) in previously healthy, HIV-negative individuals is increasingly recognized. We administered a healthcare associated quality of life (QOL) survey to the largest longitudinally followed cohort of these patients in the United States. We identified moderate or severe self-reported impairment in at least one QOL domain in 61% of subjects at least one year following diagnosis. Self-reported cognitive impairment was noted in 52% and sleep disturbance was noted in 55%. This is the first comprehensive study of cross-sectional long-term QOL in previously healthy patients following cryptococcal infection.
Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
Authors: Fujita Shiro , Masago Katsuhiro 
Published: February 2021

AbstractBoth non-small-cell lung cancer cases in never-smokers and nonmedullary thyroid cancer cases have been increasing in developed countries. Some studies have shown an excess of co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. We aimed to clarify the underlying genetic factors that contribute to the occurrence of these two malignancies. We performed germline exome sequencing in a cohort of 9 patients with the two malignancies. In terms of candidate genes, we performed target resequencing, immunohistochemistry, and microsatellite instability testing on another cohort. Two rare missense heterozygous variants in MSH6 were identified and verified by Sanger sequencing. One available tumour specimen showed heterogeneous MSH6 status in immunohistochemistry. Further exploration with different cohorts (a total of 8 patients with the two malignancies) demonstrated that 2 out of 8 patients had a germline missense or promotor variant of MLH1 and four out of 10 tumour specimens revealed heterogeneous immunohistochemistry staining in any of the four mismatch repair proteins: MLH1, PMS2, MSH2 and MSH6. Although our cohort showed a different disease profile than Lynch syndrome, this study suggests causal roles of impaired DNA mismatch repair capacity in non-small-cell lung cancer and nonmedullary thyroid cancer.
NIR self-powered photodetection and gate tunable rectification behavior in 2D GeSe/MoSe2 heterojunction diode
Authors: Hussain Muhammad , Jaffery Syed Hassan Abbas , Ali Asif , Nguyen Cong Dinh , Aftab Sikandar , Riaz Muhammad , Abbas Sohail , Hussain Sajjad , Seo Yongho , Jung Jongwan 
Published: February 2021

AbstractTwo-dimensional (2D) heterostructure with atomically sharp interface holds promise for future electronics and optoelectronics because of their multi-functionalities. Here we demonstrate gate-tunable rectifying behavior and self-powered photovoltaic characteristics of novel p-GeSe/n-MoSe2 van der waal heterojunction (vdW HJ). A substantial increase in rectification behavior was observed when the devices were subjected to gate bias. The highest rectification of ~ 1 × 104 was obtained at Vg = − 40 V. Remarkable rectification behavior of the p-n diode is solely attributed to the sharp interface between metal and GeSe/MoSe2. The device exhibits a high photoresponse towards NIR (850 nm). A high photoresponsivity of 465 mAW−1, an excellent EQE of 670%, a fast rise time of 180 ms, and a decay time of 360 ms were obtained. Furthermore, the diode exhibits detectivity (D) of 7.3 × 109 Jones, the normalized photocurrent to the dark current ratio (NPDR) of 1.9 × 1010 W−1, and the noise equivalent power (NEP) of 1.22 × 10–13 WHz−1/2. The strong light-matter interaction stipulates that the GeSe/MoSe2 diode may open new realms in multi-functional electronics and optoelectronics applications.
Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
Authors: Gao Huashan , Zhao Qian , Tang Shanshan , Li Kaiying , Qin Fujian , Song Ziwei , Pan Yi , Jin Liang , Zhang Yanfeng 
Published: February 2021

AbstractMultiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type 1 diabetes through immunomodulation. Therefore, we designed a new dual-functional PGLP-1-VP, which is expected to combine the anti-inflammatory effect of PGLP-1 and the immunomodulatory effect of VP peptide. In streptozotocin-induced hyperglycemic mice model, we demonstrated that PGLP-1-VP can act as a GLP-1R agonist to improve hyperglycemia and increase insulin sensitivity. In the NOD mouse model, PGLP-1-VP treatment reduced morbidity, mortality, and pancreatic inflammation, and showed superior effect to PGLP-1 or VP treatment alone, confirming that PGLP-1-VP may act as a dual-function peptide. PGLP-1-VP provided immunomodulatory effect through increasing Th2 cell percentage and balancing the ratio of Th2/Th1 in spleen and PLN, similar to P277 and VP. Additionally, PGLP-1-VP and PGLP-1 act the anti-inflammation by increasing Treg cells and TGF-β1 content like DPP-IV inhibitor. Taken together, our data shows that the dual-functional PGLP-1-VP reduces morbidity and mortality in the NOD model, suggesting a potential role in preventing and treating type 1 diabetes.
Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
Authors: Weglarz-Tomczak Ewelina , Tomczak Jakub M. , Talma Michał , Burda-Grabowska Małgorzata , Giurg Mirosław , Brul Stanley 
Published: February 2021

AbstractAn efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PLpro) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PLpro. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PLproCoV2. Furthermore, we identified, for the first time, inhibitors of PLproCoV2 showing potency in the nanomolar range. Moreover, we found a difference between PLpro from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.
Selective loss of microvesicles is a major issue of the differential centrifugation isolation protocols
Authors: Nigro Annamaria , Finardi Annamaria , Ferraro Marzia M. , Manno Daniela E. , Quattrini Angelo , Furlan Roberto , Romano Alessandro 
Published: February 2021

AbstractMicrovesicles (MVs) are large extracellular vesicles differing in size, cargo and composition that share a common mechanism of release from the cells through the direct outward budding of the plasma membrane. They are involved in a variety of physiological and pathological conditions and represent promising biomarkers for diseases. MV heterogeneity together with the lack of specific markers had strongly hampered the development of effective methods for MV isolation and differential centrifugation remains the most used method to purify MVs. In this study, we analysed the capacity of the differential centrifugation method to isolate MVs from cell-conditioned medium using flow cytometry and TEM/AFM microscopy. We found that the loss of MVs (general population and/or specific subpopulations) represents a major and underestimate drawback of the differential centrifugation protocol. We demonstrate that the choice of the appropriate rotor type (fixed-angle vs swinging-bucket) and the implementation of an additional washing procedure to the first low-speed centrifugation step of the protocol allow to overcome this problem increasing the total amount of isolated vesicles and avoiding the selective loss of MV subpopulations. These parameters/procedures should be routinely employed into optimized differential centrifugation protocols to ensure isolation of the high-quantity/quality MVs for the downstream analysis/applications.
Supercritical carbon dioxide decellularization of plant material to generate 3D biocompatible scaffolds
Authors: Harris Ashlee F. , Lacombe Jerome , Liyanage Sumedha , Han Margaret Y. , Wallace Emily , Karsunky Sophia , Abidi Noureddine , Zenhausern Frederic 
Published: February 2021

AbstractThe use of plant-based biomaterials for tissue engineering has recently generated interest as plant decellularization produces biocompatible scaffolds which can be repopulated with human cells. The predominant approach for vegetal decellularization remains serial chemical processing. However, this technique is time-consuming and requires harsh compounds which damage the resulting scaffolds. The current study presents an alternative solution using supercritical carbon dioxide (scCO2). Protocols testing various solvents were assessed and results found that scCO2 in combination with 2% peracetic acid decellularized plant material in less than 4 h, while preserving plant microarchitecture and branching vascular network. The biophysical and biochemical cues of the scCO2 decellularized spinach leaf scaffolds were then compared to chemically generated scaffolds. Data showed that the scaffolds had a similar Young’s modulus, suggesting identical stiffness, and revealed that they contained the same elements, yet displayed disparate biochemical signatures as assessed by Fourier-transform infrared spectroscopy (FTIR). Finally, human fibroblast cells seeded on the spinach leaf surface were attached and alive after 14 days, demonstrating the biocompatibility of the scCO2 decellularized scaffolds. Thus, scCO2 was found to be an efficient method for plant material decellularization, scaffold structure preservation and recellularization with human cells, while performed in less time (36 h) than the standard chemical approach (170 h).
Load-sharing biomechanics of lumbar fixation and fusion with pedicle subtraction osteotomy
Authors: La Barbera Luigi , Wilke Hans-Joachim , Ruspi Maria Luisa , Palanca Marco , Liebsch Christian , Luca Andrea , Brayda-Bruno Marco , Galbusera Fabio , Cristofolini Luca 
Published: February 2021

AbstractPedicle subtraction osteotomy (PSO) is an invasive surgical technique allowing the restoration of a well-balanced sagittal profile, however, the risks of pseudarthrosis and instrumentation breakage are still high. Literature studied primary stability and posterior instrumentation loads, neglecting the load shared by the anterior column, which is fundamental to promote fusion early after surgery. The study aimed at quantifying the load-sharing occurring after PSO procedure across the ventral spinal structures and the posterior instrumentation, as affected by simple bilateral fixation alone, with interbody cages adjacent to PSO level and supplementary accessory rods. Lumbar spine segments were loaded in vitro under flexion–extension, lateral bending, and torsion using an established spine tester. Digital image correlation (DIC) and strain-gauge (SG) analyses measured, respectively, the full-field strain distribution on the ventral surface of the spine and the local strain on posterior primary rods. Ventral strains considerably decreased following PSO and instrumentation, confirming the effectiveness of posterior load-sharing. Supplemental accessory rods considerably reduced the posterior rod strains only with interbody cages, but the ventral strains were unaffected: this indicates that the load transfer across the osteotomy could be promoted, thus explaining the higher fusion rate with decreased rod fracture risk reported in clinical literature.
Double-layered fiber for lightweight flexible clothing providing shielding from low-dose natural radiation
Authors: Kim Seon-Chil , Son Jun Sik 
Published: February 2021

AbstractNatural and medical radiation are the most frequent sources of daily low-dose radiation exposure for the general public, but these radiation levels are generally acceptable. Among various occupations, aviation crew members and medical workers are exposed to high levels of radiation from scattered rays. This study focused on developing clothing for shielding aviation crew members from natural radiation during air travel. Materials were selected considering their radiation-shielding properties. A tungsten double-layered composite yarn and a polyethylene terephthalate (PET) fiber fabric containing BaSO4 were manufactured. The characteristics and shielding performances of the products were analyzed. Prototypes of a protective scarf (for shielding the thyroid gland) and apron (for shielding the torso) for flight attendants were produced. A lightweight fabric was produced that neither restricts the movement of the wearer nor causes them skin discomfort. The shielding performances of the tungsten composite and PET fiber fabrics containing BaSO4 were 0.018 mmPb and 0.03 mmPb, respectively, demonstrating low-dose shielding that may be useful for protecting aviation crew members from scattered rays. The characteristics of the developed fibers are comparable to those of materials used in clothing production; therefore, low-dose radiation-shielding clothing could be manufactured for use in aviation, medical, and other industries.