bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium circumsporozoite protein enhances the efficacy of gefitinib in lung adenocarcinoma cells by inhibiting autophagy via proteasomal degradation of LC3B
Authors: Lu Xiao , Zhang Jiao , Liu Quanxing , Zhou Dong , Deng Xufeng , Yang Guixue , Li Manyuan , Liu xiaoqing , Dai Jigang , Zheng Hong 
Published: August 2021

Abstract
Background: Almost all patients with lung adenocarcinoma (LUAD) develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, LDH, flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, the apoptosis rate, and stemness. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and Western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cyclohexane, MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and stemness were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib . When LUAD cells were treated with the ubiquitin-specific inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro . Conclusions: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.
Nonlinear characteristics of a multi-degree-of-freedom wind turbine’s gear transmission system involving friction
Authors: Zhang Qiang , Wang Xiaosun , Cheng Shaobo , Xie Fuqi , Wu Shijing 
Published: August 2021

Abstract
In this study, a 42-degree-of-freedom (42-DOF) translation-torsion coupling dynamics model of the wind turbine’s compound gear transmission system considering time-varying meshing friction, timevarying meshing stiffness, meshing damping, meshing error and backlash is proposed. Considering the different meshing between internal and external teeth of planetary gear, the time-varying meshing stiffness is calculated by using the cantilever beam theory. An improved mesh friction model takes account into the mixing of elastohydrodynamic lubrication (EHL) and boundary lubrication to calculate the time-varying mesh friction. The bifurcation diagram is used to analyze the bifurcation and chaos characteristics of the system under the excitation frequency as bifurcation parameter. Meanwhile, the dynamic characteristics of the gear system are identified from the time domain diagrams, phase diagrams, Poincare maps and amplitude-frequency spectrums of the gear system. The results show that the system has complex bifurcation and chaotic behaviors including periodic, quasi-periodic, chaotic motion. The bifurcation characteristics of the system become complicated and the chaotic region increases considering the effects of friction in the high frequency region.
Giant Primary Apocrine Carcinoma of Frontal Region: Clinical Presentation, Surgical Treatment and Review of the Literature
Authors: Popović Dragana Petrović , Novaković Marijan , Stojičić Milan , Brašanac Dimitrije , Elbaz Mirjana Petrović , Nikolić-Živanović Maja 
Published: August 2021

Abstract
Background: Primary cutaneous apocrine carcinoma (PCAC), a subtype of sweat gland carcinoma, is an extremely rare malignant neoplasm. Distinguishing apocrine carcinoma from breast carcinoma metastasis is difficult even for pathologist. Most arise in regions of high apocrine gland density like axilla, and rarely on the scalp and eyelid, but it’s possible to occur elsewhere on the skin. Primary cutaneous apocrine carcinoma of the scalp is a rare malignancy most often reported in the literature as case reports or small case series. Giant form of primary cutaneous apocrine carcinoma in frontal region is not described in literature, to the best of our knowledge. There no established protocols for primary cutaneous apocrine carcinoma treatment.Case presentation: We report a case giant primary cutaneous apocrine carcinoma localized in frontal region. Definitive diagnosis of primary cutaneous apocrine carcinoma is made by biopsy with microscopic and immunohistochemical analysis. Wide surgical excision and reconstruction with large local transposition flap and split thickness skin grafts for secondary defect were our therapy of choice.Conclusion: Primary cutaneous apocrine carcinoma is very rare malignancy and giant form in not described yet. Surgical treatment provided the patients with the tumor free status as well satisfactory aesthetical appearances and quality of living.
Soil moisture as determinant of the seasonal soil co2 emission: evidence from central siberia
Authors: Makhnykina Anastasia Vladimirovna , Tychkov Ivan Ivanovich , Prokushkin Anatoly Stanislavovich , Pyzhev Anton Igorevich , Vaganov Eugene Alexandrovich 
Published: August 2021

Abstract
Background

The soils of the boreal zone contain significant reserves of carbon, therefore, their response to current climate changes will significantly affect the sustainability of forest ecosystems and the future concentration of CO 2 in the atmosphere. When modeling soil emission, it is necessary to focus on the main soil environment factors. In this paper, a simple exponential model of the soil CO 2 emissions growth was modified by introducing an additional parameter - the threshold soil moisture in different types of ecosystems based on the direct measurements.

Results

The developed model adequately reflects the dynamic changes in soil emission for different types of ecosystems. This result was achieved by including moisture as a second environmental factor besides temperature, describing changes in soil CO 2 emissions during the summer period. The error of direct measurements for all measuring seasons was about 20% of the values of direct measurements of the CO 2 flux. Note that such a high error was observed once per season in early and mid-June, reaching 60-80% on some days. Our models demonstrate in the season with the highest amount of precipitation the smallest differences in modeled fluxes about 15-20%, which indirectly indicates that the emission flux is not inhibited by insufficient moisture in this season.

Conclusions

The final model application depends on the characteristics of the microclimatic conditions of a particular ecosystem, namely, a factor that has a limiting effect on the biological processes. When studying the functional role of boreal forest ecosystems the moisture conditions consideration is crucial to explain the atmospheric CO 2 emission processes.
Topical instillation of cell-penetrating peptide-conjugated melphalan blocks metastases of retinoblastoma
Authors: Jiang Kuan , Fan Xingyan , Hu Yang , Yao Shengyu , Liu Yu , Zhan Changyou , Lu Weiyue , Wei Gang 
Published: August 2021

Abstract
Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved comparable tumor inhibition effects to intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases. In contrast, the mice treated with intravitreally injected melphalan suffered more brain metastases related death, probably due to the “inside-out” diffusion of injected melphalan expelling the tumor outside the eye. The ocular absorption of 89WP-conjugated melphalan and other small molecules, both hydrophobic and hydrophilic, occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.
Droplet Nuclei Caustic Formations In Exhaled Vortex Rings
Authors: Papoutsakis Andreas , Gavaises Manolis 
Published: August 2021

Abstract
Vortex ring structures occur in light or hoarse cough configurations. These instances consist of short impulses of exhaled air resulting to a self-contained structure that can travel large distances. The present study is the first implementation of the second order Fully Lagrangian Approach (FLA) for three-dimensional realistic flow-fields obtained by means of Computational Fluid Dynamics (CFD) and provides a method to calculate the occurrence and the intensity of caustic formations. The carrier phase flow field is resolved by means of second order accurate Direct Numerical Simulation (DNS) based on a Finite Difference approach for the momentum equations, while a spectral approach is followed for the Poisson equation using Fast Fourier Transform (FFT). The effect of the undulations of the carrier phase velocity due to large scale vortical structures and turbulence is investigated. The evaluation of the higher order derivatives needed by the second order FLA is achieved by prefabricated least squares second order interpolations in the three dimensions. The method allows for the simulation of the clustering of droplets and droplet nuclei exhaled in ambient air in conditions akin to light cough. Given the ambiguous conditions of vortex-ring formation during cough instances, three different formation numbers n = UT /D are assumed, i.e. underdeveloped (n = 2), ideal (n = 3.7) and over-developed VRs (n = 6). The formation of clusters results in the spatial variance of the airborne viral load. This un-mixing of exhumed aerosols is related to the formation of localised high viral load distributions that can be linked to super-spreading events.
miR-188-3p-targeted Regulation of ATG7 Affects Cell Autophagy in Patients With Non-obstructive Azoospermia
Authors: Wang Yuan , Tian Chengcheng , Jiao Yunyun , Liu Minrui , Ma Xueshan , Jin Haixia , Su Yingchun , Zhang Xiangyang , Niu Wenbin , Yao Guidong , Sun Yingpu , Song Wenyan 
Published: August 2021

Abstract
Background: Studies have found that ATG7 knockout mice have defects in acrosome development, and the sperm formed by them are similar to human round-headed sperm. miR-188-3p expression is alleviated in the testis tissues of NOA samples. It is unclear whether ATG7 gene is related to non-obstructive azoospermia and whether miR-188-3p and ATG7 have direct target regulation relationship to affect spermatogenesis.Methods: The testicular tissues of 14 non-obstructive azoospermia (NOA) patients and 13 healthy patients were collected for basic scientific research from October 2017 to June 2018. High-throughput sequencing, qRT-PCR, Western blot, immunohistochemical staining, immunofluorescence, electron microscope, and luciferase experiment were performed to confirm the correlation between miR-188-3p and ATG7 in non-obstructive azoospermia.Results: ATG7 was highly expressed in NOA group. ATG7 protein was localized in the cytoplasm of spermatogenic cells at various levels, and the expression in NOA group was dramatically higher than that of normal individuals. After overexpression of miR-188-3p, the ATG7 3'UTR-WT luciferase activity was impeded; while the ATG7 3'UTR-MUT luciferase activity had no significant difference. LC3 and Beclin-1 gene and protein expression in the NOA samples were elevated in comparison with the normal samples; LC3 was mainly located in the cytoplasm of spermatogenic cells at all levels. LC3 and Beclin-1 genes expression after miR-188-3p overexpression were prominently in comparison with the normal samples; after miR-188-3p was inhibited, LC3 and Beclin-1 expressions were dramatically higher. The degree of LC3 punctate aggregation in the miR-188-3p mimic NC samples was greater, and that in the miR-188-3p inhibitor group was greater. The number of autophagosomes of the miR-188-3p mimic samples was less compared with the mimic NC group.Conclusion: We demonstrated here that the ATG7 gene was located in all levels of spermatogenic cells and was highly expressed in the NOA group. The expression of ATG7 gene was negatively correlated with miR-188-3p that may regulate the target gene ATG7 to participate in autophagy and affect the occurrence of NOA.
Assessment of Plasma Neurofilament Light as a Biomarker of Neuronal Injury in Young Adults with Perinatal HIV Infection
Authors: Ruiz-Saez Beatriz , Martín-Bejarano Manuela , Aragon Ana Martínez , Gisslen Magnus , Zetterberg Henrik , Blennow Kaj , de Ory Santiago Jiménez , Alvarez-Losada Susana , Muñoz-Fernández Mª Angeles , Melero Helena , Ramos Jose Tomás , Navarro Maria Luisa , González-Tomé Maria Isabel 
Published: August 2021

Abstract
Background: Higher plasma concentration of neurofilament light (pNfL) is associated with neurodegeneration. However, to our knowledge, up to now, there are no data in HIV patients with infection due to vertical transmission. This is the first study to report pNfL in a cohort of HIV perinatally infected (PHIV) young adults compared with non-HIV (HIV-) controls.Methods: Thirty-three PHIV patients and 25 age-matched HIV- were recruited to this cross-sectional study. Plasma NfL concentrations were compared between both groups. In a subgroup of 48 participants (25 PHIV patients and 23 HIV-), brain volumes through magnetic resonance imaging (MRI) and neuropsychological testing (NT), were also conducted and compared with pNfL values.Plasma NfL concentration was measured using Single Molecule Array (Simoa) immunoassay.NT included fluid intelligence and processing speed through the WAIS-IV Coding subtest, and the Stroop Test.ResultsFifty-eight participants were included, median age 20.7 years [IQR 17.8-23.4]. 100% of the patients were under antiretroviral treatment (cART) and 85% had viral load <50 copies/ml.Although no statistically significant differences were found between patients and controls regarding pNfL concentration, there was a trend towards higher levels in patients with viral load >50 copies/ml.With regard to brain volumes and NT, in the PHIV group, lower white matter volumes and lower score in the coding subtest were associated with higher pNfL values. ConclusionsMost PHIV adolescents under cART have similar levels of pNfL than HIV-. As reported in adults, those with HIV-RNA >50 copies/ml showed higher values and lower white matter volumes that may imply an ongoing CNS injury. Plasma NfL could be a feasible biomarker of CNS injury in PHIV patients with unsuppressed viral load.
High Mortality Among Patients With Severe COVID-19 and Do-not-intubate Orders Despite Use of Remdesivir and Dexamethasone
Authors: Holm Nanna , Israelsen Simone Bastrup , Lund Tamara Theresia , Kristiansen Klaus Tjelle , Krogh-Madsen Rikke , Benfield Thomas , Kronborg Gitte 
Published: August 2021

Abstract
Background Moderate to severe respiratory distress among patients with coronavirus disease 2019 (COVID-19) is associated with a high mortality. Dexamethasone and remdesivir were introduced in the second wave of COVID-19 in Denmark. Methods This is a retrospective study of patients with COVID-19 and a supplemental oxygen requirement of ≥15 Liters per minute (L/min). The patients were divided in two groups corresponding to the first- and second wave of COVID-19 and analysed regarding need of ventilator support and mortality dependent on orders to Do Intubate (DI) or Do Not Intubate (DNI), respectively. Results The study included 178 patients. The mortality was 24% for patients with DI orders (n=115) and 81% for patients with DNI orders (n=63) increasing to 98% (n=46) for patients with DNI orders and very high flow oxygen requirements (≥30 L/min). Use of constant continuous positive airway pressure (cCPAP) increased from 71% in the first wave to 91% in the second wave (p<0.001) whereas the use of mechanical ventilation (MV) decreased from 54% to 28% (p=0.005). Conclusion The mortality was high for patients with DNI orders and respiratory distress with very high levels in supplemental oxygen in both the first and second wave of COVID-19 despite treatment with dexamethasone and remdesivir and improved prognosis for patients with DI orders. Hence careful evaluation on transition to palliative care must be considered for these patients. Study Registration The study was retrospectively registered and approved by the Danish Patient Safety Authority (record no. 31-1521-309) and the Regional Data Protection Center (record no. WZ20017637-2020-37).
Simulating Dynamic Facial Expressions of Pain From Visuo-Haptic Interactions With a Robotic Patient
Authors: Tan Yongxuan , Rérolle Sibylle , Lalitharatne Thilina Dulantha , Zalk Nejra Van , Jack Rachael E. , Nanayakkara Thrishantha 
Published: August 2021

Abstract
Medical training simulators can provide a safe and controlled environment for medical students to practice their physical examination skills. Visual feedback of involuntary pain expressions in response to physical palpation on an affected area of a patient is an important source of information for physicians. However, most existing robotic medical training simulators that can capture physical examination behaviours in real-time cannot display facial expressions or comprise a limited range of patient identities in terms of ethnicity and gender. Together, these limitations restrict the utility of medical training simulators because they do not provide medical students with a representative diversity both of pain facial expressions and face identities, which could result in biased practice. Further, these limitations restrict the utility of such medical simulators to be used to detect and correct early signs of bias in medical training. Here, for the first time, we present a robotic system that can simulate facial expressions of pain in response to palpations, displayed on a range of patient face identities. We use the unique approach of modelling dynamic pain facial expressions using the data-driven psychophysical method of reverse correlation and incorporating the visuo-haptic interactions of users performing palpation to a robot medical simulator. Specifically, participants performed palpation actions on the abdomen phantom of simulated patients, which triggered the real-time display of 6 pain-related facial Action Units (AUs) on a robotic face (MorphFace), each controlled by two pseudo randomly generated transient parameters: rate of change β and activation delay τ. Participants then rated the appropriateness of the facial expression displayed in response to their palpations on a 4-point scale. Each participant (n = 16, 4 Asian female, 4 Asian male, 4 White female and 4 White male) performed 200 palpation trials on 4 patient identities (Black female, Black male, White female and White male) simulated using MorphFace. Results showed that a gradual decrease of β and increase of τ from upper face AUs (around the eyes) to those in the lower face (around the mouth) is rated to be appropriate by all participants. We found that transient parameter values that generated the appropriate pain facial expressions as rated by participants, palpation forces, and delays between palpation actions varied across gender and ethnicity of participant-simulated patient pairs. These findings suggest that gender and ethnicity biases affect the participants’ palpation strategies and their perception of the pain facial expressions displayed on MorphFace. We anticipate our approach could be utilised to generate physical examination models with diverse patient demographic groups to reduce erroneous judgments in medical students, and provide focused training to address these errors.
Trend Analysis of Hydro-meteorological Parameters in the Jhelum River Basin, North Western Himalayas
Authors: umar Sheikh , Lone M A , Goel N K , Zakwan Mohammad 
Published: August 2021

Abstract
The Jhelum River basin drains the entire Kashmir valley and is susceptible to floods, surrounded Himalayan Mountain range. The trend analysis of Hydro-meteorological data is crucial for planning and management of various activities (agriculture, design of hydraulic structures) in the basin. The purpose of the present study is to analyze the trends in the annual maximum and annual average discharge, annual maximum, and annual average rainfall for the Jhelum River basin. The trend analysis was performed by using Mann-Kendall (M-K), Sen’s slope, and innovative trend analysis (ITA) at various Hydro-meteorological stations. The outcomes of trend analysis using the ITA test showed non-monotonic trends at various stations for different time series data and bring forth more significant data to analyze changes in Hydro-meteorological data. Moreover, the overall trend shows a significant decreasing trend in annual average rainfall and discharge, while annual maximum rainfall and discharge revealed a significant increasing trend via ITA. The trend analysis depicts changes in Hydro-meteorological data which would be useful for future management of water resources. Moreover, changes in the discharges in the Jhelum River are due to climatic change and anthropogenic activities in the basin.
Auditory Time Thresholds for Subsecond but not Suprasecond Stimuli are Impaired in ADHD
Authors: Anobile Giovanni , Bartoli Mariaelisa , Pfanner Chiara , Masi Gabriele , Cioni Giovanni , Tinelli Francesca 
Published: August 2021

Abstract
Background. The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. Methods. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds for both subsecond (0.5-1s) and suprasecond (0.75-3s) stimuli. Results. Results showed a severe impairment in ADHD for subsecond thresholds (Log10BF=1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. Suprasecond thresholds were indistinguishable between the two groups (Log10BF = –0.5) and not correlated with subsecond thresholds. Conclusions. Since much evidence suggest that perception of subsecond stimuli does not load on cognitive control and working memory, the current results are consistent with a pure timing deficit in individuals with ADHD.