bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupled Eulerian-Lagrangian Simulation of Indexable Drilling
Authors: Svensson Daniel , Andersson Tobias , Lassila Andreas Andersson
Published: December 2021

This paper presents finite element simulations of indexable drilling of AISI4140 workpieces. The Coupled-Eulerian-Lagrangian framework is employed and the focus is to predict the drilling torque around the hole axis, thrust force, temperature distributions and chip geometries. The cutting process is modelled separately for peripheral and central insert. Then, the total thrust force and torque are predicted by superposing the predicted result for each insert. Experiments and simulations are conducted at a constant rotational velocity of 2400 rpm and feed rates of 0.13, 0.16 and 0.18 mm/rev. While the predicted torques are in excellent agreement, the thrust forces showed discrepancies of 12 - 20% to the experimental measured data. Effects of the friction modelling on the predicted torque and thrust force are outlined and possible reasons for the thrust force discrepancies are discussed in the paper. Additionally, the simulations indicate that the tool and workpiece temperature distributions are virtually unaffected by the feed rate.
Paleoclimate-induced stress on polar forested ecosystems prior to the Permian–Triassic mass extinction
Authors: Gulbranson Erik , Mellum Morgan , Corti Valentina , Dahlseid Aidan , Atkinson Brian , Ryberg Patricia , Cornamusini Gianluca
Published: December 2021

The end Permian extinction (EPE) has been considered to be contemporaneous on land and in the oceans. However, re-examined floristic records and new radiometric ages from Gondwana indicate a nuanced terrestrial ecosystem response to EPE global change. Paleosol geochemistry and climate simulations indicate paleoclimate change likely caused the demise of the widespread glossopterid ecosystems on Gondwana. Here, we evaluate the climate response of plants to the EPE via dendrochronology to produce annual-resolution records of tree ring growth for a succession of Late Permian and early Middle Triassic fossil forests from Antarctica. Paleosol geochemistry provides a broader context paleoclimate history. The plant responses to this paleoclimate change were accompanied by enhanced stress during the latest Permian. These results suggest that paleoclimate change during the Late Permian exerted significant stress on high-latitude forests, consistent with the hypothesis that climate change was likely the primary driver of the extinction of the glossopterid ecosystems.
Scarf and Akin Osteotomies for Correction of Hallux Abducto Valgus. A Ten-year Retrospective Patient Evaluation From Five Podiatric Surgery Centres Using PASCOM PSQ-10.
Authors: Clee Sharon , Flanagan George , Pavier Julian , Reilly Ian
Published: December 2021

BackgroundCorrective surgery for hallux abducto valgus is one of the most commonly performed elective procedures in foot and ankle practice, with over a hundred different surgical solutions having been proposed throughout the literature. The purpose of the study was to identify the clinical and patient reported outcomes following Scarf-Akin osteotomies from five podiatric surgery centres over a ten-year period.MethodThis is a retrospective review from five podiatric surgical units which looked at patients who underwent Scarf osteotomies (in isolation or in combination with Akin procedures) over a ten-year period. Data was collected from the patient satisfaction questionnaires of the PASCOM-10 audit tool, which were completed by the patient six months post operatively, and further analysed using Microsoft Excel spreadsheet software.ResultsA total of 1351 patients were recorded undergoing Scarf (with or without an Akin) osteotomy for hallux abducto valgus, with 1227 females (90.83%) and 124 males (9.17%) identified but with only 1189 who had completed the patient satisfaction questionnaire. 96.8% of patients felt that their foot was either ‘better’ or ‘much better’ following surgery and that their original expectations of surgery had been met. Over 75% of patients had no post-operative sequalae identified, with metatarsal fracture noted to be the highest sequalae at 4.8%.ConclusionFrom the five podiatric surgery units reviewed, Scarf osteotomies (with or without an Akin osteotomy) for hallux abducto valgus correction, have a high level of patient satisfaction with low post-operative sequalae.Level of clinical evidenceIV (retrospective review).
Respiratory MUC5B Disproportion is Involved In Severe Community-Acquired Pneumonia
Authors: Fan Lu , Lu Yi , Wang Yan , Zhang Xiaomin , Wu Yuxuan , Sun Hao , Zhang Jinsong
Published: December 2021

Background: Mucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity.Methods: A total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity.Results: MUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92 – 25.79) vs. SCAP 8.20 µg/ml (IQR 4.97 – 14.03), p=0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15 - 1.10) vs. SCAP 0.68 mg/ml (IQR 0.46 - 1.69), p=0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50% - 5.56%) vs. SCAP 1.38% (IQR 0.73% - 1.76%), p<0.001]. MUC5B/total protein ratio was negatively correlated with total protein concentration (rs= -0.576, p<0.001), IL6 (rs= -0.312, p= 0.001), IL10 (rs= -0.228, p=0.013) , IL17 (rs= -0.282, p=0.002) and CURB-65 score (rs= -0.239, p=0.009). Logistic regression identified that MUC5B/total protein ratio, IL6 level and CURB-65 score as independent variables related to CAP severity. ROC curve demonstrated best assessment value of MUC5B/total protein ratio for SCAP (AUC 0.803, p<0.001), with a sensitivity of 88.9% and a specificity of 64.4%.Conclusions: Respiratory MUC5B disproportion is related to CAP severity. MUC5B/total protein ratio may serve as an assessment marker and a potential therapeutic target for severe CAP.
Radical Resection and Reconstruction in Patients With Adenoid Cystic Carcinoma in the Minor Salivary Glands of the Palate
Authors: Chen Wei-liang , Wang Yan , Zhou Bin , Liao Juan-kun , Chen Rui
Published: December 2021

Background: This study evaluated the clinical outcomes of the patients with adenoid cystic carcinoma (ACC) of the minor salivary glands of the palate. Methods: Forty-four patients with stage I–II disease and 14 patients with stage III–IV disease underwent radical excision and reconstruction with a facial-submental artery island flap (FSAIF) and titanium mesh plus a free anterolateral thigh flap (ALTF) and radiotherapy respectively. Patients with stage III–IV disease subsequently received cobalt Co 60 adjuvant radiotherapy. Ki-67 expression was determined semiquantitatively in 52 patients with ACC by based on the cytoplasm staining intensity and percentage of positively stained tumor cells.Results: The median (range) follow-up was 32.9 (14–58) months. Forty-one (71.7%) patients survived without disease recurrence. Nine patients (15.5%) survived with recurrent tumors (four with local recurrence, three with regional recurrence requiring salvage surgery, and two with distant metastasis); among these patients, five had overlapping recurrence. Eight patients (13.8%) died of regional, distant, or multiorgan metastasis (range: 22–42 months). The overall median (95% CI) survival time was 32.5 (25.0–39.5) months, and the median (95% CI) progression-free survival time was 32.9 (28.5–36.9) months. Rates of survival and recurrence differed significantly between patients with low- and high-grade tumors, patients with clinical stage I–II disease and those with stage III–IV disease, patients with and without lymph node metastasis, patients who underwent radical excision with versus without radiotherapy, and patients with low and high Ki-67 expression. Conclusion: Radical resection and reconstruction with FSAIF is the most suitable treatment for stage I–II ACC of the minor salivary glands of the palate. Stage III–IV tumors require radical resection, reconstruction with titanium mesh and free ALTF, and radiotherapy.
Evaluation of Plasma-Assisted Noninvasive Surgery (PANIS) as a New Technique for Sublimating Large Benign Conjunctival Nevus with Amniotic Membrane Transplantation (AMT); A Clinical Case Report
Authors: Nejat Farhad , Jadidi Khosrow , Eghtedari Shima , Moradi Maryam , Nabavi Nazanin Sadat
Published: December 2021

Background: conjunctival nevi are benign ocular lesions with a low risk of malignant transformation to melanoma. Due to cosmetic reasons patients usually consider surgical removal options. In this case report, we are presenting a new approach using plasma-assisted noninvasive surgery (PANIS) with amniotic membrane transplantation (AMT) to sublimate the nevus border and fuse the AMT with the remaining conjunctiva.Case presentation: A 33-year-old man with a history of large conjunctival nevus in his left eye, that its benignity was proved by an expert ophthalmologist through years of examination, has visited our center in September 2020. Plasma spots were used to sublimate the nevus border and fuse AMT with the conjunctiva. The patient was discharged fully satisfied without any complications and no recurrences were seen in a year of follow-up. Visual parameters were not significantly changed while the Ocular Surface Disease Index (OSDI) was reduced dramatically. Conclusion: Conjunctival nevi removal using the PANIS method with AMT is a safe, minimally invasive, and inexpensive therapeutic option. Plasma spots are suitable for AMT adhesion to the remaining conjunctiva after the nevus removal.
Ghost imaging with electron microscopy inspired, non-orthogonal phase masks
Authors: Kallepalli Akhil , Stellinga Daan , Sun Ming-Jie , Bowman Richard , Rotunno Enzo , Grillo Vincenzo , Padgett Miles
Published: December 2021

Transmission electron microscopes (TEM) achieve high resolution imaging by raster scanning a focused beam of electrons over the sample and measuring the transmission to form an image. While a TEM can achieve a much higher resolution than optical microscopes, they face challenges of damage to samples during the high energy processes involved. Here, we explore the possibility of applying computational ghost imaging techniques adapted from the optical regime to reduce the total, required illumination intensity. The technological lack of the equivalent high-resolution, optical spatial light modulator for electrons means that a different approach needs to be pursued. Using the optical equivalent, we show that a simple six-needle charged device to modulate the illuminating beam, alongside a novel reconstruction method to handle the resulting highly non-orthogonal patterns, is capable of producing images comparable in quality to a raster-scanned approach with much lower peak intensity.
Motorized 2-3 Wheelers Death Rates Over a Decade: A Global Study
Authors: Yasin Yasin J , Grivna Michal , Abu-Zidan Fikri
Published: December 2021

Background: Motorized 2-3 wheelers-related death are high due to the exposed body of the driver/passenger and the high speed. The United Nation (UN) Decade of Action for road safety aimed to reduce road traffic deaths by 50% by the year 2020. We aimed to study the factors affecting the death rates of motorized 2-3 wheelers injuried victims and whether the reduction of the death rates has met the UN target.Methods: Data were retrieved from the WHO Global Status Reports on Road Safety published over 2009 to 2018 which covered the years of 2007 to 2016. Studied variables included motorized 2-3 wheelers death rates, percentage of helmet-wearing rate, helmet law enforcement, speed law enforcement, gross national income per capita, vehicles/person ratio, motorized 2-3 wheelers/person ratio. A mixed linear model was used to define factors affecting the change of motorized 2-3 wheelers death rates over time.Results: Global mortality rates of motorized 2-3 wheelers increased by 6.5% over 10 years which was not statistically significant. Factors that affected mortality included GNI (p=0.025), motorized 2-3 wheelers per person ratio (p < 0.0001), percentage of helmet wearing rate (p=0.046), and the interaction between vehicle/person ratio and motorized 2-3 wheelers/person ratio (p=0.016). There was a significant increase in the death rates over time in the low-income countries (170.2 %, p=0.019, Friedman test), and middle-income countries (56.1 %, p < 0.0001, Friedman test), compared with a significant decrease in the high-income countries (17.8 %, p < 0.0001, Friedman test). Conclusions: Global mortality of motorized 2-3 wheelers has increased by 6.5% over a recent decade. The UN target of reducing death was not met. The increase was related to the increase of motorized 2-3 wheelers per person ratio and economic inequiety which has to be addressed globally. The economic global gap significantly impacts the mortality rates of motorized 2-3 wheelers.
Larval Transcriptomic Responses of a Stony Coral, Acropora Tenuis, During Initial Contact with the Native Symbiont, Symbiodinium Microadriaticum
Authors: Yoshioka Yuki , Yamashita Hiroshi , Suzuki Go , Shinzato Chuya
Published: December 2021

Although numerous dinoflagellate species (Family Symbiodiniaceae) are present in coral reef environments, Acropora corals tend to select a single species, Symbiodinium microadriaticum, in early life stages, even though this species is rarely found in mature colonies. In order to identify molecular mechanisms involved in initial contact with native symbionts, we analyzed transcriptomic responses of Acropora tenuis larvae at 1, 3, 6, 12, and 24 h after their first contact, together with inoculation using non-native symbionts, including the non-symbiotic S. natans and the occasional symbiont, S. tridacnidorum. Some gene expression changes were detected in larvae inoculated with non-native symbionts 1 h post-inoculation (hpi)), but those returned to baseline levels afterward. In contrast, we found that the number of differentially expressed genes gradually increased in relation to inoculation time when larvae were exposed to native symbionts. As a specific response to native symbionts, upregulation of pattern recognition receptor-like and transporter genes, and suppression of cellular function genes related to immunity and apoptosis, were exclusively observed. These findings indicate that coral larvae recognize differences between symbionts, and when the appropriate symbionts infect, they coordinate gene expression to establish stable mutualism.
Role of DNA Methylation in Mechanisms of Anterograde Amnesia
Authors: Solntseva Svetlana , Nikitin Vladimir , Kozyrev Sergey , Nikitin Pavel
Published: December 2021

Previously, we found that impairment of conditioned food aversion memory consolidation or reconsolidation in snails by NMDA glutamate receptors antagonists led to the induction of amnesia changing over time. In particular, at the later amnesia stages (10 or more days), repeated aversion training for the same food type that was used in the initial training did not induce long-term memory formation. In these animals, long-term aversion memory for a new food type was formed. We characterized this amnesia as specific anterograde amnesia. In the present work, using DNA methyltransferases (DNMT) inhibitors, the DNA methylation processes role in mechanisms of anterograde amnesia and recovery from amnesia was investigated. It was found that in amnestic animals, DNMT inhibitor administration before or after repeated training led to the rapid long-term conditioned food aversion memory formation. It depended on proteins and mRNA synthesis at certain time windows. Thus, protein synthesis inhibitors administration before or immediately after repeated training, or RNA synthesis inhibitor injection after training, prevented memory formation induced by the DNMT inhibitor. The effects of DNMT inhibitors were specific for certain conditioned stimulus, since these inhibitors did not affect amnestic animals training for a new food stimulus. DNMT inhibition during second training removed blockade of these genes' expression, opening up access to them for transcription factors synthesized during training. Thus, this work was the first to study the molecular mechanisms of anterograde amnesia, as well as memory recovery, which can be important for search for pharmacological correction of this neuropsychic pathology.
Kuala Lumpur Train Collision During the COVID-19 Pandemic
Authors: Idrose Alzamani M. , Abu-Zidan Fikri M. , Roslan Nurul Liana , Hashim Khairul Izwan M. , Adibi Saiyidi Mohd Azizi Mohd , Wahab Mahathar Abd.
Published: December 2021

Background: Two city trains collided in an underground tunnel on 24th May 2021 at the height of Covid-19 pandemic near the Petronas Towers, Kuala Lumpur, Malaysia immediately after the evening rush hours. We aim to evaluate the management of this mass casualty incident highlighting the lessons learned to be used in preparedness for similar incidents that may occur in other major cities worldwide. Methods: Information regarding incident site and hospital management response were analysed. Data on demography, triaging, injuries and hospital management of patients were collected according to a designed protocol. Challenges, difficulties and their solutions were reported. Results: The train's emergency response team (ERT) has shut down train movements towards the incident site. Red zone (in the tunnel), yellow zone (the station platform) and green zone (outside the station entrance) were established. The fire and rescue team arrived and assisted the ERT in the red zone. Incident command system was established at the site. Medical base station was established at the yellow zone. 214 passengers were in the trains. 64 of them were injured. They had a median (range) ISS of 2 (1-43) and all were sent to Hospital Kuala Lumpur (HKL). Six (9.4%) patients were clinically triaged as red (critical), 19 (29.7%) as yellow (semi-critical) and 39 (60.9%) as green (non-critical). HKL's disaster plan was activated. All patients underwent temperature and epidemiology link assessment. Seven (10.9 %) patients were admitted to the hospital (3 to the ICU, 3 to the ward, and 1 to a private hospital as requested by the patient), while the rest 56 (87.5%) (56) were discharged home. Six (9.4%) needed surgery. The Covid-19 tests were conducted on seven patients (10.9%) and was negative There were no deaths. Conclusions: The mass casualty incident was handled properly because of a clear standard operating procedure, smooth coordination between multi-agencies and the hospitals, presence of a'binary' system for 'Covid risk' and 'non-Covid risk' areas, and the modifications of the existing disaster plan. Preparedness for MCIs is essential during pandemics.
LncRNA-mRNA Expression Pattern in Invasive Pituitary Adenomas: A Microarray Analysis
Authors: Peng Chao , Wang Shuaikai , Yu Jinxiu , Deng Xiaoyi , Chen Zhishan , Ye Huiyu , Yao Hongru , Cai Hanjia , Li Yanli , Yuan Yong
Published: December 2021

Backgrounds: Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression of various cancer types; however, their roles in the development of invasive pituitary adenomas (PAs) remain to be investigated.Methods: lncRNA microarray was performed in three invasive and three noninvasive PAs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and coexpression networks between lncRNA and mRNA were constructed. Furthermore, three differentially expressed lncRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PA samples. The diagnostic values of these three lncRNAs were further evaluated by receiver operating characteristic (ROC) analysis.Results: A total of 8872 lncRNAs were identified in invasive and paired noninvasive PAs using lncRNA microarray. Among these, the differentially expressed lncRNAs included 81 that were upregulated and 165 that were downregulated. GO enrichment and KEGG pathway analysis showed that these differentially expressed lncRNAs were associated with post-translational modifications of proteins. Furthermore, we performed target gene prediction and coexpression analysis. The interrelationships between the lncRNAs and mRNAs with significant differential expression were identified. Additionally, three differentially expressed lncRNAs were selected for validation in 41 PA samples by qRT-PCR. The expression levels of FAM182B, LOC105371531, and LOC105375785 in the invasive PAs were significantly (P < 0.05) lower than in the noninvasive PAs, and these results were consistent with the microarray data. ROC analysis suggested that FAM182B and LOC105375785 expression levels could be used to distinguish invasive PAs from noninvasive PAs.Conclusion: Our findings demonstrated the lncRNAs expression patterns in invasive PAs. Thus, FAM182B and LOC105375785 may be involved in the invasiveness of PAs and serve as new candidate biomarkers for the diagnosis of invasive PAs.
Cooperative Attack-Defense Decision-Making of Multi-UAV Using Satisficing Decision-Enhanced Wolf Pack Search Algorithm
Authors: Zhou Tongle , Chen Mou , Wang Yuhui , Zhu Ronggang , Yang Chenguang
Published: December 2021

Unmanned Aerial Vehicles (UAVs) have shown their superiority for applications in complicated military missions. A cooperative attack-defense decision-making method based on satisficing decision-enhanced wolf pack search (SDEWPS) algorithm is developed for multi-UAV air combat in this paper. Firstly, the multi-UAV air combat mathematical model is provided and the attack-defense decision-making constraints are defined. Besides the traditional air combat situation, the capability of UAVs and target information including target type and target intention are all considered in this paper to establish the air combat superiority function. Then, the wolf pack search (WPS) algorithm is used to solve the attack decision problem. In order to improve efficiency, the satisficing decision theory is employed to enhance the WPS to obtain the satisficing solution rather than optimal solution. The simulation results show that the developed method can realize the cooperative attack decision-making.
Development and Analysis of a Predictive Nomogram Assessing Cancer Risk in a Chinese Cohort of Patients Presenting with Pulmonary Nodules
Authors: Liao Zufang , Zheng Rongjiong , Li Ni , Shao Guofeng
Published: December 2021

Background: Lung cancer is a major global threat to public health for which a novel prognostic nomogram is urgently needed.Patients and methods: Here, we designed a novel prognostic nomogram using a training dataset consisting of 178 pulmonary nodules for design and 124nodules for external validation. The R ‘caret’ package was used to separate patients for design into two groups, including a training cohort (n=126) for model construction and an internal validation cohort (n=52). Optimal feature selection for this model was achieved using the least absolute shrinkage and selection operator regression (LASSO) model. C-index values, calibration plots, and decision curve analyses were used to gauge the discrimination, calibration, and clinical utility, respectively, of this predictive model. Validation was then performed with the validation cohort.Results: A predictive nomogram was successfully constructed incorporating hypertension status, plasma fibrinogen levels, serum uric acid (SUA) levels, triglyceride (TG) and high-density lipoprotein (HDL) levels, density, spicule sign, ground-glass opacity (GGO), and pulmonary nodule size. This model exhibited good discriminative ability, with a C-index value of 0.795 (95% CI: 0.720–0.870), and was well-calibrated. When we used the validation cohort to evaluate the model, the C-indexes were 0.886 (95% CI: 0.800–0.972) and 0.817 (95% CI: 0.747–0.897) for internal validation and external validation, respectively. Decision curve analyses indicated the clinical value of this predictive nomogram when used at a lung cancer possibility threshold of 9%.Conclusion: The nomogram constructed in this study, which incorporates hypertension status, plasma fibrinogen levels, SUA, TG, HDL, density, spicule sign, GGO status, and pulmonary nodule size was able to reliably predict lung cancer risk in this Chinese cohort of patients presenting with pulmonary nodules.
Impact of Remote Teaching on Japanese Medical University Students' Sleeping Habits : a Longitudinal Study
Authors: Hori Reiko , Shibata Eiji , Okajima Iwao , Matsunaga Masahiro , Umemura Tomohiro , Narisada Akihiko , Suzuki Kohta
Published: December 2021

Background: The coronavirus disease 2019 (COVID-19) pandemic has changed our daily life. Owing to the imposed restrictions, many educational facilities have introduced remote teaching. This study aims to understand the impact of remote teaching on Japanese university students' sleeping habits.Methods: The participants were medical university students. We used data from an ongoing longitudinal sleeping habits survey. For 684 participants who enrolled in the university during 2018–2020, multilevel analyses of sleep duration during weekdays and weekends across 3 years were conducted, adjusting for gender, grade, place of stay, sleep problems and lifestyle habits. Results: Among the participants, 356 male (mean ± standard deviation: 22 ± 3, 18–37 years old) and 288 female (22 ± 3, 18–32 years old) students in 2018, 365 male (24 ± 3,18–36 years old) and 284 female (22 ± 2, 18–33 years old) students in 2019, and 226 male (20 ± 3,18-36 years old) and 167 female (21 ± 2, 18–34 years old) students in 2020 answered the questionnaire. The mean sleep duration during weekdays (in minutes) was 407.6 ± 60.3 in 2018, 406.9 ± 63.0 in 2019, and 417.3 ± 80.9 in 2020. The mean sleep duration during weekends (in minutes) was 494.5 ± 82.5 in 2018, 488.3 ± 87.9 in 2019, and 462.3 ± 96.4 in 2020. The analysis showed that sleep duration during weekdays was associated with the place of stay and survey year. Moreover, students reported significantly longer sleep duration during weekdays in 2020 than 2019, but no significant difference in sleep duration between 2018 and 2019. Sleep duration during weekends was found to be associated with the survey year, gender and always doing something before going to bed. Sleep duration during weekends was shorter in 2020 than 2019 and longer in male students and students who always do something before going to bed. Ten students were reported to have a delayed sleep phase in 2020. Conclusions: Students' sleep duration increased during weekdays and decreased during weekends in 2020. This difference could be explained by the COVID-19 pandemic and the introduction of remote teaching.
Following the SPARC: tracking Secreted Protein Acidic and Rich in Cysteine associated with LX-2´s extracellular vesicles as a non-destructive modality to evaluate lipid-based antifibrotic treatments
Authors: Zivko Cristina , Fuhrmann Kathrin , Fuhrmann Gregor , Luciani Paola
Published: December 2021

Uncovering the complex cellular mechanisms underlying hepatic fibrogenesis, a highly dynamic and active process ultimately responsible for liver failure if left untreated, could expedite the development of effective treatments and noninvasive diagnostic modalities for this often silent pathology. The biochemical complexity of extracellular vesicles (EVs) and their role in intercellular communication make them an attractive tool to look for biomarkers that might become a viable alternative to invasive liver biopsies. We developed a solid set of methods to isolate and characterize EVs from differently treated human hepatic stellate cell (HSC) line LX-2 in vitro, and we investigated the biological effect they exert onto naïve LX-2, proving that EVs do play an active role in fibrogenesis. Electrical/asymmetric flow field-flow fractionation (EAF4) revealed EV subpopulations with different physicochemical behaviors. Proteomic data from our samples was mined for EV-associated proteins whose expression correlated with HSC treatment. Consequently, we chose the secreted protein acidic and cysteine rich (SPARC), a matricellular protein previously reported to be upregulated in activated HSCs, as a proof-of-concept protein to explore the feasibility of using fluorescence nanoparticle tracking analysis as a non-destructive tool for the determination of HSCs’ fibrogenic phenotype based on EVs. We could thus use EVs to directly evaluate the efficacy of treatment with S80, a lipid rich (>75 %) in polyenylphosphatidylcholines (PPC). We found that PPC-rich S80 reduces the relative presence of SPARC-positive EVs. For the first time, we could correlate the cellular response to lipid-based antifibrotic treatment to the relative presence of a candidate protein marker associated with the released EVs. In addition to providing novel insights into PPC treatments, our findings pave the way for more precise and less invasive diagnostic analyses of hepatic fibrogenesis.
The immunogenicity and safety of different COVID-19 booster vaccination following CoronaVac or ChAdOx1 nCoV-19 primary series
Authors: Angkasekwinai Nasikarn , Niyomnaitham Suvimol , Sewatanon Jaturon , Phumiamorn Supaporn , Sukapirom Kasama , Senawong Sansnee , Mahasirimongkol Surakameth , Toh Zheng Quan , Umrod Pinklow , Somporn Thitiporn , Chumpol Supaporn , Ritthitham Kanokphon , Chokephaibulkit Kulkanya
Published: December 2021

The appropriate COVID-19 booster vaccine following inactivated or adenoviral vector COVID-19 vaccination is unclear. We evaluated the safety and immunogenicity of different booster vaccines, inactivated (BBIBP-CorV), chimpanzee adenoviral vector (ChAdOx1), or mRNA (BNT162b2 at full (30 µg), or half (15 µg) dose) in healthy adults who received 2-dose primary series of either inactivated vaccine (CoronaVac) or ChAdOx1 8-12 weeks earlier. Overall, the adverse events for all booster vaccines were mild and moderate. Two weeks post-booster dose, the neutralising antibody titres against Delta variant in CoronaVac-prime and ChAdOx1-prime were highest with for 30µg-BNT162b2 (411 vs 470) and 15µg-BNT162b2 (499 vs 358); followed by ChAdOx1 (271 vs 69), and BBIBP-CorV (61.3 vs 49). BNT162b2 also induced higher interferon gamma response. Heterologous COVID-19 boosting vaccination with BNT162b2 is the most immunogenic following CoronaVac or ChAdOx1 primary series. A lower dose BNT162b2 may be used as booster in settings with limited vaccine supply.
Effects of Sleep Disturbance on Neuropsychological Functioning in Patients with Pediatric Brain Tumor
Authors: Chiang Jenna A. , Feghali Paulina T. , Saavedra Anita , Whitaker Ashley M.
Published: December 2021

Purpose While the effects of sleep on cognition in typically developing children are well established, there is a paucity of research in patients with pediatric brain tumor (PBT), despite their increased risk for sleep-related disturbances. The aim of this study was to examine the impact of sleep factors on patient-reported outcome (PRO) measures, including adaptive and executive functioning within this population.Methods 133 patients with PBT (52% male) ages 5-23 (x̄ = 12.8yrs; SD = 4.5yrs) underwent neuropsychological evaluation, including assessment of adaptive and executive functioning. Subjective sleep concerns, nocturnal sleep duration, and daytime sleep behavior were also collected and compared to age-based guidelines.Results Nearly 30% of patients reported subjective sleep concerns, while the sample as a whole presented with reduced nocturnal sleep duration (approximately one hour below age-based recommendations). Despite the expectation for monophasic sleep by age five, nearly half of the sample reported consistent daytime napping. With regard to functional outcomes, inadequate sleep predicted decreased adaptive functioning, F(1, 56) = 4.23, p < .05 (R2 = .07), as well as increased symptoms of executive dysfunction, F(1, 108) = 3.51, p < .05 (R2 = .03).Conclusion Patients with PBT demonstrate several aspects of abnormal sleep, which are associated with poorer long-term PROs. Further exploration of diagnostic, treatment-related, and demographic variables will be needed to better understand these relationships among patients with PBT in order to inform appropriate interventions.
A New Type of Cemented Sand-Gravel (CSG) Mixtures for Water-Tightening of Hardfill Dams
Authors: Karimi Sina , Aghajani Hamed Farshbaf
Published: December 2021

This paper aims to achieve a specific type of cemented sand-gravel mixtures with low permeability to implement in the impervious zone of hardfill dams. To this end, various mixtures are prepared by blending two native soils of sand and gravel with different amounts of kaolinite or bentonite additives in presence of various cement content. The compaction properties, uniaxial compressive strength, permeability and scanning electron microscope (SEM) images of mixtures are measured. According to the results, the cemented mixture containing 10% of kaolinite additive regardless of native soil type exhibits the maximum strength. However, the bentonite disturbs the cement hydration in the mixture, and the strength of mixtures especially with high cement content decreases with increasing the bentonite content. The permeability of mixtures is related to the amount of cement and fine additive in the mixture. The permeability of both cemented sand and gravel mixtures decreases with increasing the bentonite additive. However, the kaolinite additive has a limited influence on the permeability of cemented gravel mixtures. The lowest permeability is achieved in the mixture involving the higher amount of bentonite (with a weight ratio of 30%) in presence of adequate cement.
Genome-Wide Superior Alleles, Haplotypes and Candidate Genes Associated With Tolerance on Sodic-Dispersive Soils in Wheat (Triticum Aestivum L.)
Authors: Sharma Darshan Lal , Bhoite Roopali , Reeves Karyn , Forrest Kerrie , Smith Rosemary , Dowla Mirza A.N.N.U.
Published: December 2021

Sodic-dispersive soils have multiple subsoil constraints including poor soil structure, alkaline pH and subsoil toxic elemental ion concentration, affecting growth and development in wheat. Tolerance is required at all developmental stages to enhance wheat yield potential on such soils. An in-depth investigation of genome-wide associations was conducted using a field phenotypic data of 206 diverse Focused Identification of Germplasm Strategy (FIGS) wheat lines for two consecutive years from different sodic and non-sodic plots and the exome targeted genotyping by sequencing (tGBS) assay. A total of 39 quantitative trait SNPs (QTSs), including 18 haplotypes were identified on chromosome 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 5A, 5D, 6B, 7A, 7B, 7D for yield and yield-components tolerance. Among these, three QTSs had common associations for multiple traits, indicating pleiotropism and four QTSs had close associations for multiple traits, within 32.38 Mb. The overlapping metal ion binding (Mn, Ca, Zn and Al) and photosynthesis genes, and transcription factors (PHD-, Dof-, HTH myb-, BHLH-, PDZ_6-domain) identified are known to be highly regulated during germination, maximum stem elongation, anthesis, and grain development stages. The homozygous/biallelic SNPs having allele frequency above 30% were identified for yield and crop establishment/plants m-2. These SNPs correspond to HTH myb-type and BHLH transcription factors, brassinosteroid signaling pathway, kinase activity, ATP and chitin binding activity. These resources are valuable in haplotype-based breeding and genome editing to improve yield potential on sodic-dispersive soils.
Senescence as a Dictator of Patient Outcomes and Therapeutic Efficacies in Human Gastric Cancer
Authors: Sun Qiang , Zhou Lulin , Niu Zubiao , Wang Yuqi , Zheng You , Zhu Yichao , Wang Chenxi , Gao Xiaoyan , Gao Li-Hua , Zhang Wen , Zhang Kaitai , Melino Gerry , HUANG HONGYAN , Wang Xiao-ning
Published: December 2021

Senescence is believed to be a pivotal player in the onset and progression of tumors as well as cancer therapy. However, the guiding roles of senescence in clinical outcomes and therapy selection for patients with cancer remains obscure, largely due to the absence of a feasible senescence signature. Here, by integrative analysis of single cell and bulk transcriptome data from multiple datasets of gastric cancer patients, we uncovered senescence as a veiled tumour feature characterized by senescence gene signature enriched, unexpectedly, in the non-cancerous cells, and further identified two distinct senescence-associated subtypes based on the unsupervised clustering. Patients with the senescence subtype had higher tumor mutation loads and better prognosis as compared with the aggressive subtype. By the machine learning, we constructed a scoring system termed as senescore based on 6 signature genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2 and TNFAIP2. Higher senescore demonstrated robustly predictive capability for longer overall and recurrence-free survival in 2290 gastric cancer samples, which was independently validated by the multiplex staining analysis of gastric cancer samples on the tissue microarray. Remarkably, the senescore signature served as a reliable predictor of chemo- and immuno-therapeutic efficacies, with high-senescore patients benefited from immunotherapy while low-senescore patients were responsive to chemotherapy. Collectively, we report senescence as a heretofore unrecognized hallmark of gastric cancer that impacts patient outcomes and therapeutic efficacy.
Impact of Volume-Based Drug Procurement Policy on Drug Use Structure of Chinese Public Medical Institutions: A Difference-in-Difference Analysis of Nine Pilot Cities and Twelve Non-pilot Provinces
Authors: Lu Jiancheng , Yang Ying , Long Hongfei , Wang Jing , Shen Yuan , Cui Dan , Mao Zongfu , Li Jinghua
Published: December 2021

Background
In 2019, the Chinese government implemented the first round pilot of volume-based drug procurement in 4 municipalities and 7 sub-provincial cities, i.e. “4+7” policy. This study evaluated the impact of “4+7” policy on the use structure of policy-related drugs.
Methods
Data of China Drug Supply Information Platform (CDSIP) database was used, covering 18,636 public medical institutions from 9 pilot cities and 12 non-pilot provinces in mainland China. “4+7” policy-related drugs were selected as study samples, including 25 drugs in the “4+7” procurement List and 83 alternative drugs that have an alternative relationship with “4+7” List drugs. “4+7” List drugs were divided into bid-winning and bid-non-winning products. Drug Structure Index (DSI) was employed as the outcome variable, and higher DSI refers to the use proportion of higher-DDDc (Defined Daily Drug cost) drugs increased. Difference-in-difference (DID) method was employed to estimate the net effect of “4+7” policy.
Results
After policy intervention, the DSI of bid-winning drugs significantly decreased (β=-0.233, p<0.0001), while non-winning drugs (β = 0.177, p<0.001) and “4+7” List drugs (β = 0.050, p<0.01) increased. No significant change was found for the overall DSI of alternative drugs (β = 0.013, p>0.05), while a remarkable increase was found in primary healthcare settings (β = 0.033, p<0.05). In three post-“4+7” periods, the increments of DSI for non-winning products were 17.54% (period 1), 18.35% (period 2), and 19.66% (period 3). The DSI of “4+7” List drugs significantly increased in post-“4+7” period 2 and 3 (all p-values<0.05).
Conclusions
The use proportion of higher-DDDc bid-winning drugs significantly decreased after policy intervention. However, among drugs not involved by NCDP policy, the use proportion of higher-DDDc drugs significantly increased after policy intervention, moreover, the increment was more pronounced at the later periods of policy implementation. The clinical use monitoring and the physician’s prescription behavior supervision should be strengthened.
Safety and Efficacy of Cabozantinib for Patients with Advanced Hepatocellular Carcinoma and Child-Pugh B Liver Function: Retrospective Analysis From the CELESTIAL Randomised Controlled Trial
Authors: El-Khoueiry Anthony B. , Meyer Tim , Cheng Ann-Lii , Rimassa Lorenza , Sen Suvajit , Milwee Steven , Kelley Robin Kate , Abou-Alfa Ghassan K.
Published: December 2021

Background: Patients with hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child-Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child-Pugh B cirrhosis at Week 8. Methods: This was a retrospective analysis of adult patients with previously treated advanced HCC. Child-Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo. Results: Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child-Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child-Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18–0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25–0.76), and best response was stable disease in 57% versus 23% of patients. Conclusions: These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child-Pugh B liver function.Clinical Trial Registration: NCT01908426
Outlining the Challenges of COVID-19 Pandemic on Africa’s Maritime Industry: the Case of Marine and Seafaring Professionals
Authors: Sackey Anthony Djaba , Tchouangeup Bertrand , Lomotey Bernard , Lamptey Benjamin Lantei , Lee Raphael Ofosu-Dua , Sackey ABIGAIL Dede , Segbefia Joseph Elorm , Teye Abraham Akwertey , Quarcoo Richmond Kennedy , Bansah John , Ewedji Christabel , Wood Ekow Eduhene
Published: December 2021

Despite the ‘Key Worker’ status accorded seafarers in moments of demonstrable selflessness -ensuring, adequate supply of food, medicines, consumables like personal protective equipment (PPEs), and energy - there is a lack of genuine interest in their concerns, leading to various calls from major stakeholders such as the United Nations and International Maritime Organization. These calls associate- with various covid-19-related policies and regulations having a direct bearing on the ongoing crew change crises, maroon and overstay of contracts, poor mental health, rise in covid-19 infections and other unrelated illnesses among ship crew. Thus, to what extent are non-traditional seafaring nations of Africa being impacted? The study examines these concerns by identifying and investigating implemented covid-19 policies and regulations and their impact on maritime operations and crew ‘wellbeing;’ the contingency measures and innovations aiding mitigate responses with minimal challenges to seafarers and marine professionals. The case study approach focuses on West Africa’s maritime corridor, examining operations in Ghana, Ivory Coast, Liberia, Nigeria and Angola to a host of varied ports and offshore installations operations. Direct field observations, as well as questionnaires and interviews of expert or ‘eye witness’ account, deployed via phone calls, online social media and emails are carried out. The study finds MLC 2006 was not been complied with. Embarkation quarantine measures and testing implemented for offshore Ghana and Angola could not prevent the outbreak of cases onboard FPSO units respectively, though the process identified positive cases during quarantine. The stigma associated with positive cases amongst the crew were prevalent in the first six months of pandemic declaration. Of the survey conducted amongst 71 vessel crew, 32.14% were certain of having recorded Covid-19 positive cases on their various Jobsites, 91.06% showed support for IMO-led interventions against covid-19, 30% complained of uncertainty spared by rumours as fueling poor mental health. However, only 19% willingly addressed issues of their proximity to covid-19. Vaccine inoculations upon commencing March 2021 remained low in the region amongst marine professionals. Mitigating measures implemented include increased internet and call access, and extensive boarding protocols. In conclusion, lessons learnt within these periods of history going forward should inform the need for a comprehensively developed global emergency response contingency regulatory plan that identifies various potential threats, establishes adequate measures and make adjustment for review and amendments –to be instated only in times of global emergencies.
Functionalized Porous Nanoscale Fe3O4 Particles Supported Biochar From Peanut Shell For Pb(II) Ions Removal From Landscape Wastewater
Authors: Jin Xiaojun , Liu Renrong , Wang Huifang , Han Li , Qiu Muqing , Hu Baowei
Published: December 2021

The large amounts of heavy metal from landscape wastewater have become serious problems of environmental pollution and risks for human health. It affects the growth of plant and aquatic, and leads to the destruction of landscape. Therefore, the development of efficient novel adsorbent is a very important for treatment of heavy metal. A low-cost and easily obtained agricultural waste (Peanut Shell) was modified by nanoscale Fe3O4 particles. Then, the functionalized porous nanoscale Fe3O4 particles supported biochar from peanut shell (PS-Fe3O4) for removal of Pb(II) ions from aqueous solution was investigated. The characterization of PS-Fe3O4 composites showed that PS from peanut shell was successfully coated with porous nanoscale Fe3O4 particles. The pseudo second-order kinetic model and Langmuir model were more fitted for describing the adsorption process of Pb(II) ions in solution. The maximum adsorption capacity of Pb(II) ions removal in solution by PS-Fe3O4 composites could reach 188.68 mg/g. The adsorption process of Pb(II) ions removal by PS-Fe3O4 composites was a spontaneous and endothermic process. The adsorption mechanisms of Pb(II) ions by PS-Fe3O4 composites were mainly controlled by the chemical adsorption process. They included Fe-O coordination reaction, co-precipitation, complexation reaction and ion exchange. PS-Fe3O4 composites were thought as a low-cost, good regeneration performance and high efficiency adsorption material for removal of Pb(II) ions in solution.