bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging
Authors: Yan Yue , Chen Binlong , Yin Qingqing , Wang Zenghui , Yang Ye , Wan Fangjie , Wang Yaoqi , Tang Mingmei , Xia Heming , Chen Meifang , Liu Jianxiong , Wang Siling , Zhang Qiang , Wang Yiguang
Published: December 2021

Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65-80% and 20-35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.
Healthcare Service Utilization Patterns and Patient Experience in Persons With High Healthcare Needs: A Comparison Across 22 Countries
Authors: Bychkovska Olena , Tederko Piotr , Engkasan Julia Patrick , Hajjioui Abderrazak , Gemperli Armin
Published: December 2021

BackgroundPersons with complex health conditions, e.g. spinal cord injury (SCI), frequently visit numerous clinical settings. Their service utilization and patient experience is a comprehensive indicator of how a system is functioning overall. This study compared the patient experience of persons with chronic SCI in relation to healthcare service utilization patterns in 22 countries, hypothesizing that primary-care oriented patterns would offer better experience.MethodsThis study was based on International Spinal Cord Injury Survey with 12 588 participants from 22 countries worldwide. Utilization clusters were identified by cluster analysis, experience score was attained by partial credit model. The association between the two was explored by regression analysis. ResultsHighest share of visits was to primary care physician (18%) and rehabilitation physician (16%). Utilization patterns had diverse orientation: from primary care to specialized and from inpatient to outpatient. The experience was reported as very good and good across different dimensions: 78% reported respectful treatment; 75% – clear explanations; 71% – involvement in decision making; 63% – satisfaction with care. Average experience score on 0-100-point scale was 64, highest – 74 (Brazil) and lowest – 52 (Japan, South Korea). Service utilization patterns were associated with patient experience, but no uniformly better patient experience was found for neither primary or specialized care-oriented systems. ConclusionWhile there are distinct utilization patterns between countries of how persons with chronic SCI use the healthcare system, neither the more primary care oriented nor the specialized care system leads to a uniformly better patient experience.
A Multi-Stage Model of Cell Proliferation and Death: Tracking Cell Divisions with Erlang Distributions
Authors: Belluccini Giulia , Lopez-Garcia Martin , Lythe Grant , molina-parís carmen
Published: December 2021

Lymphocyte populations, stimulated in vitro or in vivo , grow as cells divide. Stochastic models are appropriate because some cells undergo multiple rounds of division, some die, and others of the same type in the same conditions do not divide at all. If individual cells behave independently, each can be imagined as sampling from a probability density of times to division. The most convenient choice of density in mathematical and computational work, the exponential density, overestimates the probability of short division times. We consider a multi-stage model that produces an Erlang distribution of times to division, and an exponential distribution of times to die. The resulting dynamics of competing fates is a type of cyton model. Using Approximate Bayesian Computation, we compare our model to published cell counts, obtained after CFSE-labelled OT-I and F5 T cells were transferred to lymphopenic mice. The death rate is assumed to scale linearly to the generation (number of divisions) and the number of stages of undivided cells (generation 0) is allowed to differ from that of cells that have divided at least once (generation greater than zero). Multiple stages are preferred in posterior distributions, and the mean time to first division is longer than the mean time to subsequent divisions.
Hypoxic-immune Model Based on Lung Squamous Cell Carcinoma Reveals the Effects of Inflammation and Hypoxia on Drug Resistance, CD8 Cell Depletion and Prognosis
Authors: Sun Kang , Zhang Zhiqiang , Wang Dongqin , Ma Hongyu , Lian Chaoqun , Zhang Jing
Published: December 2021

Background: Lung squamous cell carcinoma (LUSC) is a malignant tumor with high mortality and poor prognosis. More evidence shows that hypoxia and the immune environment play an essential role in cancer progression, but the specific impact on lung squamous cell carcinoma is unclear. This study mainly establishes immune and hypoxia risk models to predict the prognosis of patients and formulates personalized treatment plans for patients according to the specific conditions of hypoxia regulation and immune invasion in high-risk groups. Results: Based on the combined use of multiple data, 380 hypoxia and immune co-related genes (HMGs) were obtained， to establish the risk model of immune and hypoxia. Through the use of comprehensive analysis methods, the model has a high predictive value. The survival rate of the high-risk group is low, and the CD8-T cell depletion factor is widely distributed in high-risk groups. It has a large number of neutrophils and low CD8 cells. In addition, hypoxia, inflammation, and drug resistance-related pathways are also abundant in high-risk groups. We also found that high-risk patients were generally resistant to chemotherapeutic drugs. Finally, we constructed a competing endogenous RNA (CeRNA) network closely related to risk genes, including 9 mRNAs, 10 MicroRNAs (miRNAs), and 16 long non-coding RNAs (lncRNAs). Conclusions:This study specifically analyzed the effects of hypoxia regulation and immune Infiltration on the prognosis of patients. It provided a new idea for patients to improve the prognosis and personalized treatment.
A Novel and Atypical Nf-Kb Proinflammatory Program Regulated by A Camkii-Proteasome Axis Is Involved in the Early Activation of Muller Glia by High Glucose
Authors: Sba Diego Ph.D. Diego , Tundo Grazia Raffaella , Mecchia Alice , Palumbo Camilla , Atzori Maria Grazia , Levati Lauretta , Caccuri Anna Maria , Cascio Paolo , Lacal Pedro , Graziani Grazia , Varano Monica , Coletta Massimiliano , Parravano Maria Cristina
Published: December 2021

BackgroundDiabetic retinopathy (DR) is a microvascular complication of diabetes with a heavy impact on the life-quality of subjects and with a dramatic burden for health and economic systems on a global scale.Although the pathogenesis of DR is largely unknown, several preclinical data have pointed out to a main role of Muller glia, a cell type which spans across the retina layers providing nourishment and support for Retina Ganglion Cells (RGCs), in sensing glycemia and in acquiring a proinflammatory polarization in response to this insult.ResultsBy using a validated experimental model of DR in vitro, the rMC1 cells challenged with high glucose, we uncovered the induction of an early (within minutes) and atypical NF-kB signalling pathway regulated by a CamKII-proteasome axis. Phosphorylation of proteasome subunit Rpt6 (at serine 120) by CamKII stimulated the accelerated turnover of IkBα (i.e., the natural inhibitor of p65-50 transcription factor), regardless of the phosphorylation at serine 32 which labels canonical NF-kB signalling. This event allowed the p65-p50 heterodimer to migrate into the nucleus and to induce the selective transcription of IL-8, Il-1β and MCP-1. Pharmacological inhibition of CamKII or proteasome stopped this proinflammatory program, whereas introduction of a Rpt6 phospho-dead mutant (Rpt6-S120A) stimulated a paradoxical effect on NF-kB probably through the activation of a compensatory mechanism which may involve phosphorylation of 20S α4 subunit.ConclusionsThis study introduces a novel pathway of MG activation by high glucose and casts some light on the biological relevance of proteasome post-translational modifications in modulating pathways regulated through targeted proteolysis.
In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers
Authors: Mazari-Arrighi Elsa , Okitsu Teru , Teramae Hiroki , Aoyagi Hoshimi , Kiyosawa Mahiro , Yano Mariko , Takeuchi Shoji
Published: December 2021

Primary hepatocytes are essential cellular resource for drug screening and medical transplantation. Since culture systems for them have already succeeded in reconstituting the biomimetic microenvironment, acquiring additional capabilities both to expand primary hepatocytes and to handle them easily would be expected as progress to the next stage. This paper describes a culture system for primary rat hepatocytes that is equipped with scalability and handleability relying on cell fiber technology. Cell fibers are cell-laden core-shell hydrogel microfibers; in the core regions, cells are embedded in extracellular matrix proteins, cultured three-dimensionally, and exposed to soluble growth factors in the culture medium through the hydrogel shells. By encapsulating primary rat hepatocytes within cell fibers, we first demonstrated they increase in number while keeping their viability and their hepatic specific functions for up to thirty days of subsequent culture. Then, we demonstrated the potency of the primary rat hepatocytes that proliferate in cell fibers not only as cell-based sensors to detect drugs that damage hepatic functions and hepatocellular processes but also as transplants to improve the plasma albumin concentrations of congenital analbuminemia. Therefore, our culture system could serve for innovating strategies and promising developments in applying primary hepatocytes to both pharmaceutical and medical fields.
Deep-Learning Based Analysis of Preoperative MRI Predicts Microvascular Invasion and Outcome in Hepatocellular Carcinoma
Authors: sun Bao-Ye , Gu Pei-Yi , Guan Ruo-Yu , Zhou Cheng , Lu Jian-Wei , Yang Zhang-Fu , Pan Chao , Zhou Pei-Yun , Zhu Ya-Ping , Li Jia-Rui , Wang Zhu-Tao , Gao Shan-Shan , Yi Yong , Luo Ye , Qiu Shuang-Jian
Published: December 2021

Background & Aims:

Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC.
Methods

We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression.
Results

Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and AFP were independently associated with MVI: DL-MVI (odds ratio [OR]=35.738; 95% confidence interval [CI]: 14.027-91.056; p<0.001), AFP (OR=4.634, 95% CI: 2.576-8.336; p<0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824.
Conclusions

Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.
Clinical Non-adherence and Its Associated Factors Among HIV Positive Pediatrics Attending Care in South Gondar Zone Public Health Facilities, Northwest Ethiopia, 2021
Authors: Tiruneh Chalie Marew , Emiru Tigabu Desie , Tibebu Nigusie Selomon , Abate Moges Wubneh , Nigat Adane Birhanu , Bantie Berihun , Belete Amsalu , Walle Belete Gelaw , Legas Getasew , Getu Bisrat Dessie
Published: December 2021

Background: The most important factor in the success of HIV treatment is clinical adherence. Inadequate clinical adherence is one of the factors that affect the adherence level of highly active antiretroviral treatment and its effect on suppressed viral replication. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of clinical adherence level of HIV-infected children. Hence, this study aimed to assess clinical non-adherence level and its associated factors among HIV-positive children on HAART. Methods: A multicenter cross-sectional study was conducted from July 1 to August 30, 2021, among HIV-infected children on ART in South Gondar Zone. Data were entered into Epi Data Version 4.6 and analysis was done using Statistical Package for Social Science (SPSS) Version 25. Binary logistic regression was implemented to assess the association of factors against the outcome variable and variables with p-values ≤ 0.25 in the bivariable analysis were entered into the multivariable analysis. Finally, variables with p-values less than 0.05 were considered statistically significant factors.Result-out of 384 study participants, 383 were included in this study with a response rate of 99.7%. Nearly half of the study participants 190(49.6%) were girls. The majority, 291 (76%) of caretakers were biological mothers, and 203(53%) did not have treatment supporters. One hundred seventy-nine (46.7%) of caretakers did not disclose the status of the child about the illness. The overall prevalence of non-adherence among children on ART was 31.9 %( 95% CI: 27.2-36.6). Rural residency, diagnostic status non-disclosure, no adherence supporter, having no biological caretaker and comorbid illness were significantly associated with clinical non-adherence of HIV positive children.Conclusion-clinical non-adherence among children among HIV-positive children attending care in south Gondar zone health institutes is unacceptably high. Being rural residency, diagnostic status non-disclosure, no adherence supporter, having non-biological caretaker, and having comorbid illness were significantly associated with clinical non-adherence. Thus, attention shall be given to successful clinical adherence in HIV-positive children who uses the antiretroviral drug.
Investigation on Strain Rate Sensitivity of 3D Printed sPEEK-HAP/rGO Composites
Authors: Baligidad Sagar Mahalingappa , Gangadhara Chethan Kumar , Chandrashekhar Maharudresh Aralikatte
Published: December 2021

Nanofillers can be added to polymers to improve their mechanical behavior. However, the yield behaviour of most polymer composites is influenced by strain rate. The majority of the research focused on the behaviour of polymer composites at high strain rates. This work aims to investigate how hydroxyapatite (HAP) and reduced Graphene Oxide (rGO) nanofillers affect the mechanical properties of sulphonated polyetheretherketone (sPEEK) at low (tensile and compression behaviour) and high strain rates (compression behaviour). The thermal, mechanical, and energy absorption responses of sPEEK filled with HAP and varying mass fraction (Mf) of rGO (0.5%, 1%, and 1.5%) at different strain are studied in detail. The strong strain rate effect was seen in HAp and rGO loaded sPEEK composites. The strain rate sensitivity factor of sPEEK-HAP/rGO improved as the strain rate increased, but decreased when the Mf of rGO increased. Under low strain rate compression, HAp and rGO loaded sPEEK absorbed more energy at Mf about 4%. SEM micrography was used to study the microstructures of the fractured interfaces of the components, revealing that the HAp and sPEEK materials formed a good compatibility in presence of rGO.
Conditional Loss of Ikkα in Sp7/osterix+ Cells Has No Effect on Bone, but Leads to Cell Autonomous, Age-related Loss of Peripheral Fat
Authors: Davis Jennifer L , Pokhrel Nitin K , Cox Linda , Faccio Roberta , Veis Deborah J
Published: December 2021

NF-κB has been reported to both promote and inhibit bone formation. To further explore its role in osteolineage cells, we conditionally deleted IKKα, an upstream kinase required for non-canonical NF-κB activation, using Sp7/Osterix (Osx)-Cre. Surprisingly, we found no effect on either cancellous or cortical bone, even following mechanical loading. However, we noted that IKKα conditional knockout (cKO) mice began to lose body weight after 6 months of age with severe reductions in fat mass in geriatric animals. Low levels of recombination at the IKKα locus were detected in fat pads isolated from 15 month old cKO mice. To determine if these effects were mediated by unexpected deletion of IKKα in peripheral adipocytes, we looked for Osx-Cre-mediated recombination in fat using reporter mice, which showed increasing degrees of reporter activation in adipocytes with age up to 18 months. Since Osx-Cre-driven recombination in peripheral adipocytes increases over time, we conclude that loss of fat in aged cKO mice is most likely caused by progressive deficits of IKKα in adipocytes. To further explore the effect of IKKα loss on fat metabolism, we challenged mice with a high fat diet at 2 months of age, finding that cKO mice gained less weight and showed improved glucose metabolism, compared to littermate controls. Thus, Osx-Cre mediated recombination beyond bone, including within adipocytes, should be considered as a possible explanation for extraskeletal phenotypes, especially in aging and metabolic studies.
Systematic exploration of prognostic alternative splicing events related to immune microenvironment of Clear Cell Renal Cell Carcinoma
Authors: Deng Youyuan , Wang Jianguo , Pang Yanrui , Li Jingyong , Zhang Huaixiao , Chen Jiawei , Fang Kun , Zhou Wei , Xu Ke , Ren Tao
Published: December 2021

Background

Clear cell renal cell carcinoma (ccRCC) accounts for almost 75% of all renal cancers, with high heterogeneity and poor prognosis. There is increasing evidence that alternative splicing (AS) is associated with tumorigenesis and immune microenvironment. However, studies on the relationship between AS events and immunity in ccRCC are still few but needed.
Methods

The transcriptional data and clinicopathological information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. We grouped patients according to the ESTIMATE algorithm and identified for differentially expressed AS events (DEASs). The functional enrichment analysis and unsupervised consensus analysis were performed to investigate the association between AS events and immune features. The regulatory network of survival-related AS events and intersection SFs was used to explore potential mechanisms.
Results

In total, 515 ccRCC patients were included in the present study. The low immune-score group had longer overall survival (OS) than the high low immune-score group. 861 AS events were identified as DEASs, and they were enriched in immune-related pathways. Unsupervised clustering analysis revealed that AS-based clusters significantly corelated with prognosis and immune features of ccRCC. Finally, MBNL1 was identified as a hub SF, and it was shown to inhibit proliferation and metastasis, promote apoptosis, and block cells in G2/M phase in 786O and A498 cells.
Conclusion

The present systematic exploration elaborated that not only some critical AS events were related to prognosis and immune microenvironment of ccRCC, but also the hub SF, such as MBNL1, could affect the development and progression of ccRCC.
Long-Term Trend of Polycyclic Aromatic 1 Hydrocarbon (PAH) Concentrations in Tokyo from 2007 to 2016: Effects of Changes in PAH Emissions and Degradation.
Authors: Shimada Kojiro , Nohchi Masayuki , Maeshima Koji , Uchino Tomonori , Kobayashi Yusuke , Ono Kazuki , Ogata Hiroko , Katsumi Naoya , Inazu Koji , Okochi Hiroshi
Published: December 2021

The concentrations of polycyclic aromatic hydrocarbons (PAHs) in aerosol were measured in Shinjuku, which is central Tokyo, Japan, for 10 years from 2007 to 2016. The effects of changes in emission sources and their degradation by reaction with ozone were assessed in this study. There was no significant increasing or decreasing trend of the PAH concentrations during 10 years (P > 0.05). The average selected seven the PAH concentrations (0.88 ng m−3) during 10 years was lower than those in New York and Paris. However, the trend of ozone concentrations is increasing in central Tokyo. This inconsistency raises a question. Did the fact that the ozone concentration was higher than the PAH concentrations promote PAH degradation? To apportion the PAH sources, we used PAH concentration profiles and positive matrix factorization analysis. The contribution of vehicle emissions to the PAHs ranged from 40 to 80 %. Ozone concentrations increased by 3.70 %/year during 10 years. The theoretical degradation rates of PAHs by ozone, which were calculated using a pseudo-first-order rate equation, suggested that the lifetimes of benzo[a]pyrene (BaP) decreased by 1 min from 2007 to 2016. We investigated the aging of BaP using the profile of the isomer ratios. We found that the aging of BaP at the urban and roadside sites were nearly identical indicating aging regardless of the season. Although the decomposition of BaP is promoted by the photochemical oxidation reaction, this result suggests that a certain threshold value exists as the degree of the decomposition. This degradation of PAH can improve chemical loss processes in air quality model.
New Interpretations of The State Function of An Elementary Particle Based On The Origin of Quantum Probability
Authors: Wen Shuming
Published: December 2021

The theoretical results of quantum mechanics (QM) have been verified by experiments, but the probabilistic Copenhagen interpretation is still controversial, and many counterintuitive phenomena are still difficult to understand. To trace the origin of probability in QM, we construct the state function of a multiparticle quantum objective system and find that the probability in QM originates from the particle number distribution rate in a unit volume near position r at time t in the multiparticle quantum objective system. Based on the origin of probability, We find that the state function of the particle has precise physical meaning; that is, the particle periodically and alternately exhibits the particle state and wave state in time and space, obtain the localized and nonlocalized spatiotemporal range of the particle, the apparent trajectory of the particle motion. Based on this, through rigorous mathematical derivation and analysis, we propose new physical interpretations of the quantum superposition state, wave-particle duality, the double-slit experiment, the Heisenberg uncertainty principle, and the quantum tunnelling effect, and these interpretations are physically logical and not counterintuitive.
The Increased In Vivo Firing of Pyramidal Cells But not Interneurons in the Anterior Cingulate Cortex After Neuropathic Pain
Authors: Zhu Da-Yu , Cao Ting-Ting , Fan Hong-Wei , Zhang Ming-Zhe , Duan Hao-Kai , Li Jing , Li Yun-Qing , Wang Pan , Chen Tao
Published: December 2021

Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which is further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.
The potential contribution of projected ASEAN Power Grid to emission reduction
Authors: Budiman Ibnu , Swandaru Akbar , Suryadi Beni
Published: December 2021

This paper analyzed the potential contribution of the projected ASEAN Power Grid (APG) with increased contribution of renewable energy (RE) in the power system, toward emission reduction in South East Asia, both in region and country level, in three different scenarios (Baseline, ASEAN Target, and Optimum RE). Data collection was done with a series of (co-creation) consultation meetings with countries in the region and international energy institutes. Estimation of emission reduction from CO2 and N2O was calculated based on projected solar and wind capacity addition to replace fossil fuel consumption in the APG. We found that the potential contribution of the projected APG toward emission reduction in South East Asia is up to 112,267 million tons of CO2 and 64 thousand tons of N2O by 2040, under the optimum RE scenario. The source of that contribution is varying at the country level. Countries with potential significant contributions are Thailand, the Philippines, Vietnam, Malaysia, and Indonesia. Countries like Singapore and Brunei that have a relatively small contribution to the region, also having progressive trends to meet the RE target and its emission reduction. This trend shows a potential progressive improvement for those countries to reduce their emission from the energy sector by 2040. With their current high base scenario, they may reach a higher target in the future to integrate variable RE to the APG and contributing to emission reduction in the region.
Examining the Impact of Excessive Daytime Sleepiness on Utility Scores in Patients with Obstructive Sleep Apnoea and/or Narcolepsy in Five European Countries
Authors: Cambron-Mellott M. Janelle , Mettam Sam , Li Vicky W. , Rowland John C. , Castro JeanPierre Coaquira
Published: December 2021

Background: Excessive daytime sleepiness (EDS) is a cardinal symptom of narcolepsy and affects many patients with obstructive sleep apnoea (OSA). EDS is associated with reduced quality of life, increased accident risk, and poor workplace performance. Given the impact of EDS, the ability to predict health-related utility from sleepiness is valuable for examining the cost effectiveness of novel treatments. The aim of this study was to examine the association between EDS and EQ-5D in patients with OSA and/or narcolepsy by modelling EQ-5D utility scores from Epworth Sleepiness Scale (ESS) scores.Methods: Data were obtained from the Europe 2016/2017 National Health and Wellness Survey, an online, general population survey, designed to represent the age and gender composition of each country’s adult population. Analyses included 2,348 patients self-reporting symptomatic and diagnosed OSA (n=2,277), narcolepsy (n=48), or both (n=23). Multivariable models were used to examine ESS as a predictor of EQ-5D utility while adjusting for covariates of interest. Results were validated following the National Institute for Health and Care Excellence Decision Support Unit guidelines for predictive modeling.Results: Utility decreased as EDS severity increased (no EDS: 0.711±0.251, mild: 0.685±0.261, moderate: 0.643±0.268, severe: 0.559±0.323). Whereas participants with only OSA or only narcolepsy did not differ in utility, those with both conditions had lower scores (0.685±0.266 and 0.627±0.325 vs. 0.439±0.340, respectively). Piecewise linear regression identified a single breakpoint at ESS score of 11.29. In the final model, for each point increase in ESS score, the corresponding decrease in EQ-5D utility was larger among patients with ESS scores ≥12 compared to patients with ESS scores ≤11 (model slopes: -0.0131 vs. -0.0026, respectively). Findings from the validation sample confirmed these results.Conclusions: This study demonstrates the impact of sleepiness on quality of life (QoL) and its negative impact irrespective of sleep condition (OSA or narcolepsy). The breakpoint identified is relatively consistent with the established ESS cutoff score ≥11, which demarcates pathological sleepiness. Furthermore, as EDS severity worsens (increases) on the ESS, the impact on QoL is greater.
Quorum Sensing Mediated Pathogenicity, Virulence Genes and Class 1 Integron in Carbapenem-Resistant Clinical Pseudomonas Aeruginosa Isolates
Authors: Başkan Ceren , Sırıken Belgin , Tüfekci Enis Fuat , Kılınç Çetin , Ertürk Ömer , Erol İrfan
Published: December 2021

Carbapenems are the most effective agents for treating carbapenem-resistant clinical P. aeruginosa (CRPsA) infections. During an infection, a quorum-sensing (QS) system and its regulating virulence genes have a great role. The aim of the study was to detect the presence of a las and rhl QS system and related virulence genes and a class 1 (Cls1) integron. A total of 52 CRPsA isolates obtained from Kastamonu, Turkey was analyzed. A conventional culture method, an oprL gene-based molecular assay for P. aeruginosa isolates, and an automated VITEK-2 compact system were applied for the isolation and identification of CRPsA isolates. The oprL gene was detected in all of the isolates tested. At least one of the las or rhl system genes was detected in 98.07% of the isolates, and the percentage of las system genes (98.07%) were higher than that of rhl system genes (90.38%). algD, lasB, toxA and aprA genes were detected in between 46.15% and 88.46% of the isolates, and co-existence of four genes were detected in 40.38% of the isolates. Cls1 integron and slime production using Congo Red Agar (CRA) were present in 51.92% and 67.30%, respectively, of the isolates. There was a significant positive correlation (p <.10) between the las system and the rhl system and a strongly positive correlation (p<.01 or p <.05) between the rhl system-four virulence genes and slime production-and among some virulence genes. In conclusion, the CRPsA isolates tested in the study are highly virulent and QS systems have a significant role in pathogenesis.
Potential Room Temperature Superconductivity in Clathrate Lanthanide/Actinides Octadechydrides at Extreme Pressures
Authors: Zhong Xin , Sun Ying , Iitaka Toshiaki , Xu Meiling , Liu Hanyu , Chen Changfeng , Ma Yanming
Published: December 2021

Atomic metallic hydrogen (AMH) hosting high-temperature superconductivity has long been considered a holy grail in condensed matter physics and attracted great interest, but attempts to produce AMH remain in intense exploration and debate. Meanwhile, hydrogen-rich compounds known as superhydrides offer a promising route toward creating AMH-like state and property, as showcased by the recent prediction and ensuing synthesis of LaH10 that hosts extraordinary superconducting critical temperatures (Tc) of 250-260 K at 170-190 GPa. Here we show via advanced crystal structure search a series of hydrogen-superrich clathrate compounds MH18 (M: rare-earth/actinide metals) comprising H36-cage networks, which are predicted to host Tc up to 329 K at 350 GPa. An in-depth examination of these extreme superhydrides offers key insights for elucidating and further exploring ultimate phonon-mediated superconductivity in a broad class of AMH-like materials.
Trisomy 18 – When the Diagnosis Is Compatible With Life
Authors: Silva Catarina , Ferreira Mariana Cortez , Saraiva Jorge , Cancelinha Cândida
Published: December 2021

Trisomy 18 is an autosomal chromosomal disorder characterized by the presence of an extra 18 chromosome. In the last decades, and as the therapeutic options have become more relevant, the medical community witnessed a paradigm shift on the offer of treatment to these children.This is a retrospective, cohort study that strives to characterize the clinical path and survival of the children with the diagnosis of trisomy 18, accompanied in a tertiary pediatric hospital between 1995 and 2020.Six children were identified with trisomy 18, two of them mosaic (33,3%) and four were females (66,7%). All had cardiovascular, cognitive and physical development anomalies or minor congenital anomalies (n=6, 100%) and most presented musculoskeletal anomalies (n=5, 83,3%) and feeding difficulties (n=4, 66,7%). Four children (66,7%) were reliant on devices or equipment and all needed chronic medication (n=6, 100%). Two children (33,3%) were submitted to surgical interventions. Four children (66,7%) were hospitalized in the last year of life. A decision of limitation of therapeutic effort was present in three cases (50%) with one child being referenced to pediatric palliative care (16,7%). One-month, one-year and ten-year survival were 66,7% (n=4), 33,3% (n=2, both mosaic), and 16,7% (n=1, mosaic) respectively.Conclusions: Knowledge on the clinical picture is of great importance regarding the neonatal care and the decisions about invasive treatments, which can involve ethical issues, highlighting, concurrently, the need for attempted referral of these children to pediatric palliative care teams.
Stability analysis of rock slope and calculation of rock lateral pressure in foundation pit with structural plane and cave development
Authors: Xu Jin , Wang Yansen
Published: December 2021

In this study, numerical simulations were carried out to analyze the influence of caves in different positions and shapes, in combination with structural planes, on the stability of the slope and the failure characteristics of a rock slope in a deep foundation pit with high inclination structural planes and cave development. The schemes for substituting a single karst cave for karst caves were constructed. Based on the penetration failure characteristics of karst caves between parallel structural planes, methods for calculating the safety factor of the rock foundation pit and the upper bound of the lateral pressure of the supporting structure under the combined influence of the caves and structural planes were developed, which can be used to assess the safety factor of a rock mass and to calculate the lateral pressure under complex geological conditions.
Socio-economic Study of Conservation and Rehabilitation of Tropical Peatland With Agroforestry Systems in Central Kalimantan, Indonesia
Authors: Elia Andrie , Jaya Adi , Antang Emmy Uthanya , Octora Merrisa , Indrajaya Kusnida , Dohong Salampak
Published: December 2021

Current studies on tropical peatlands in Indonesia are mostly focused on the impacts of management practices on the environment. Studies on efforts to conserve and rehabilitate the degradation of tropical peatland involving farmers through agroforestry systems have been limited. By employing the qualitative survey with semi-structured interviews and field observations to agroforestry locations in two villages of Tumbang Nusa and Kalampangan, Central Kalimantan, Indonesia aims to fill those research gaps. The results showed that the main motivation of farmers in starting agroforestry activities was the understanding that there would be limited trees in the future, and planting trees with a combination of intercrops provided adequate income. Agroforestry farmers who devote considerable time to agroforestry can meet the family's economic needs. Although further guidance is not typically provided, government intervention through tree planting programs also stimulates agroforestry activities. Intensive management of intercrops in various types can provide a good income. For intensive intercropping options, farmers follow market demand, while less intensive farmers prefer plants that do not require intensive management. Trees planted in agroforestry systems are only given fertilizer at the initial planting stage. Some farms receive fertilizer subsidies from government support programmes, but fertilizers are obtained from intercropping at the following stage. The study results imply that the community needs to get knowledge and training on agroforestry, which can be a way of conserving and rehabilitating tropical peatlands and a source of income.
Species Assemblage of Birds’ Community in Protected Areas of Delhi-NCR
Authors: chatrath deepali , Bhatt Lipakshi , Sethy Janmejay , Murthy Meesala K.
Published: December 2021

Green spaces in cities especially in the capital city of India provide necessary recreational, social and psychological benefits to stressing residents of the city. Cities and towns depict the extreme human-modified environments with only remnants of the original habitats present. Study undertaken to know the abundance, diversity and species richness of avian fauna in urban protected landscapes of Delhi, NCR. In the following paper, the methods include data is extracted from e-Bird of past 40 years to illustrate the changing trend of bird species from 1980-2019 from 7 greenspaces of Delhi-NCR which are Aravalli Biodiversity Park, Asola Bhatti Wildlife Sanctuary, Deer Park, Dheerpur Wetland, National Zoological Park, Northern Ridge, Okhla Bird Sanctuary, Sanjay Van, Yamuna Biodiversity Park and analysed as box plots using PAST. The result showed a varied trend from 1980-2019, which included the usage of e-Bird by the period. The result indicated that the recent decade is well updated with data on e-Bird, hence several birds’ individual is maximumly observed from 2011-2019. The study has shown the wavy trend from 1980-2019 in species composition in the capital city of India. This also suggest that people have started recording observation on a single platform and shown interest in last decade. This study will lead to taking the necessary step to maintain the avian biodiversity in the green spaces of the capital city- Delhi-NCR.
A Molecular View of Amyotrophic Lateral Sclerosis Through the Lens of Interaction Network Modules
Authors: Jensen Klaus Højgaard , Stalder Anna Katharina , Wernersson Rasmus , Roloff-Handschin Tim-Christoph , Hansen Daniel Hvidberg , Groenen Peter MA
Published: December 2021

Background: Despite the discovery of familial cases with mutations in Cu/Zn-superoxide dismutase (SOD1), Guanine nucleotide exchange C9orf72, TAR DNA-binding protein 43 (TARDBP) and RNA-binding protein FUS as well as a number of other genes linked to Amyotrophic Lateral Sclerosis (ALS), the etiology and molecular pathogenesis of this devastating disease is still not understood. As proteins do not act alone, conducting an analysis of ALS at the system level may provide new insights into the molecular biology of ALS and put it into relationship to other neurological diseases.Methods: A set of ALS-associated genes/proteins were collected from publicly available databases and text mining of scientific literature. We used these as seed proteins to build protein-protein interaction (PPI) networks serving as a scaffold for further analyses. From the collection of networks, a set of core modules enriched in seed proteins were identified. The molecular biology of the core modules was investigated, as were their associations to other diseases. To assess the core modules’ ability to describe unknown or less well-studied ALS biology, they were queried for proteins more recently associated to ALS and not involved in the primary analysis.Results: We describe a set of 26 ALS core modules enriched in ALS-associated proteins. We show that these ALS core modules not only capture most of the current knowledge about ALS, but they also allow us to suggest biological interdependencies. In addition, new associations of ALS networks with other neurodegenerative diseases, e.g. Alzheimer’s, Huntington’s and Parkinson’s disease were found. A follow-up analysis of 140 ALS-associated proteins identified since 2014 reveals a significant overrepresentation of new ALS proteins in these 26 disease modules.Conclusions: Using protein-protein interaction networks offers a relevant approach for broadening the understanding of the biological context of known ALS-associated genes. Using a bottom-up approach for the analysis of protein-protein interaction networks is a useful method to avoid bias caused by over-connected proteins. Our ALS-enriched modules cover most known biological functions associated with ALS. The presence of recently identified ALS-associated proteins in the core modules highlights the potential for using these as a scaffold for identification of novel ALS disease mechanisms.
Topic overlap and research waste at the ‘Overviews of systematic reviews’ level: a meta-research study
Authors: Lunny Carole , Zhang Jia He , Chen Alyssa , Neelakant Trish , Shinger Gavindeep , Stevens Adrienne , Tasnim Sara , Sadeghipouya Shadi , Adams Stephen , Zheng Yi Wen , Lin Lester , Yang Pei Hsuan , Dosanjh Manpreet , Ngsee Peter , Ellis Ursula , Shea Beverley J. , Reid Emma K. , Wright James M.
Published: December 2021

Background
Multiple ‘overviews of reviews’ conducted on the same topic (“overlapping overviews”) represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews.
Methods
MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesised reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview topics according to 22 WHO ICD-10 medical classifications, overviews as broad or narrow in scope, and overlap as identical, nearly identical, partial, or subsumed. Subsummation was defined as when broad overviews subsumed the populations, interventions and at least one outcome of another overview.
Results
Of 541 overviews included, 169 (31%) overlapped across similar PICO, fell within 13 WHO ICD-10 medical classifications, and 62 topics. 148/169 (88%) overlapping overviews were broad in scope. Fifteen overviews were classified as having nearly identical overlap (9%); 123 partial overlap (73%), and 31 subsumed (18%) others.
Conclusions
One third of overviews overlapped in content and a majority covered broad topic areas. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time and effort across medical disciplines. Authors of overviews can use this study and the sample of overviews to identify gaps in the evidence for future analysis, and topics that are already studied which do not need to be duplicated.
A Rare Cause of Septic Shock Secondary to Trauma: Morel Lavallée Lesion - Case Report
Authors: Gunay Mehmet , Mollavelıoglu Baran , Gok Kaan Ali Fuat , Ilhan Mehmet , Ertekın Cemalettın
Published: December 2021

Introduction Morel Lavallée lesion is a hemolymphatic collection in between muscular fascia that can be caused by the separation of soft tissue and muscular fascia in degloving fashion. Morel Lavallée lesion is an infrequent lesion but should be known for medico-legal reports Morel Lavallée is a rare presentation that can cause life-threatening septic and hemorrhagic shock. Case PresentationIn this case report we are going present Morel Lavallée lesion which can present with septic shock and bleeding and can be mortal. Our patient, fourty seven years old male, arrived at the emergency department with an ambulance 1 hour after an extravehicular traffic accident. Apart from a right hemopneumothorax with multiple rib fractures, grade 2 laceration in spleen and bilateral kidneys, zone 2 fracture of sacrum, computer tomography (CT) revealed a closed, degloving injury of the pelvis , also known as a Morel-Lavallée lesion. On CT, Morel Lavallée lesion appear as well-defined, encapsulated fluid collections that occasionally show fluid fluid levels .. Heavy fluid collection was detected in control CT which was actually a collection infected hematoma in the operative setting. Patient was diagnosed in the first 12 hours and necrotic tissues were debrided. Patient was considered deceased after 15 days without any improvement in his GCS score.ConclusionsThere is one report that describe mortality after Morel Lavallée lesion in the autopsy setting. Early diagnosis and treatment are essential to decrease severity of necrosis and sepsis though our patient has deceased due to complications of sepsis
A Comparison of Survival after Radiosurgery in Non-Small Cell Lung Cancer Patients with One versus More than Twenty Brain Metastases
Authors: Wei Zhishuo , Niranjan Ajay , Abou-Al-Shaar Hussam , Deng Hansen , Albano Luigi , Lunsford L. Dade
Published: December 2021

Background

Whether the number or cumulative volume of brain metastases affects survival in patients with metastatic non-small cell lung cancer (NSCLC) remains controversial. We sought to compare whether patients with solitary brain disease had better outcomes than patients with ≥ 20 brain metastases.
Methods

Between 2014 to 2020, 26 NSCLC patients (925 tumors) underwent stereotactic radiosurgery (SRS) for ≥ 20 metastases in a single procedure (median margin dose = 16 Gy, median cumulative tumor volume = 4.52 cc); 56 patients underwent SRS for a single metastasis (median margin dose = 18 Gy, median volume = 4.74 cc). The overall survival (OS), local tumor control (LC), adverse radiation effect (ARE) risk, and incidence of new tumor development were compared.
Results

No difference in OS was found between patients with ≥ 20 brain metastases (median OS = 15 months) and patients with solitary metastasis (median OS = 12 months; p = 0.3). In the solitary tumor cohort, two of 56 (3.5%) tumors progressed whereas in the ≥ 20 cohort only 3 of 925 (0.3%) tumors showed progression (*p = 0.0013). The rate of new tumor development was significantly higher in patients with ≥ 20 tumors (***p = 0.0001). No significant difference of ARE rate was found (7.5% for ≥ 20 tumors vs. 8.7% for single metastasis).
Conclusions

Patients with ≥ 20 tumors showed significantly better LC with similar OS compared to patients with solitary tumors. Current guidelines that restrict the role of SRS to patients with 1-4 tumors should be revised.
approach to polarity sensitivity and negative concord by lexical underspecification
Authors: Tonhauser Judith
Published: December 2021

This paper presents a dynamic semantic approach to the licensing of Polarity Sensitive Items (PSIs) and n-words of Negative Concord. We propose that PSIs are unified by the semantic scale property, which is responsible for their sensitivity to the context; we develop a semantic licensing analysis based on Fauconnier's (1975) scales and Ladusaw's (1979) notion of entailment. The first part of the paper concludes with a formalization of semantic licensing in the sense of Ladusaw (1979) within HPSG (see, e.g., Pollard & Sag (1994)) which allows for a uniform treatment of the licensing of PSIs and n-words of Negative Concord and accounts for the disambiguating nature of PSIs in scopally ambiguous sentences.

The second part of the paper is concerned with the limitations of semantic licensing, which, we claim, needs to be sensitive to the context. We present the discussions of, e.g., Heim (1984) and Israel (1996) with respect to the importance of the context in particular licensing constellations, and then turn to linearity constraints on licensing. We present data from German which may not be accounted for by linearity constraints and sketch an analysis for this data which supports the necessity of context-sensitive semantic licensing.