bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a highly potent pan-RAF inhibitor IHMT-RAF-128 for cancer treatment
Authors: Wang Aoli , Liu Juan , Li Xixiang , Zou Fengming , Qi Ziping , Qi Shuang , Liu Qingwang , Wang Zuowei , Cao Jiangyan , Jiang Zongru , Wang Beilei , Ge Juan , Wang Li , Wang Wenchao , Liu Jing , Liu Qingsong
Published: December 2022

Although RAS mutations occur in about 30% of solid tumors, targeting RAS mutations other than KRAS-G12C is still challenging. As an alternative approach, developing inhibitors targeting RAF, the downstream effector of RAS signaling, is currently one of the main strategies for cancer therapy. Selective BRAF-V600E inhibitors Vemurafenib, Encorafenib, and Dabrafenib have been approved by FDA and received remarkable clinical responses, but these drugs are ineffective against RAS mutant tumors due to limited inhibition on dimerized RAF. In this study, we developed a highly potent pan-RAF inhibitor, IHMT-RAF-128, which exhibited similarly high affinities between RAF monomers and dimers, and showed potent anti-tumor efficacy against a variety of cancer cells harboring either RAF or RAS mutations, especially Adagrasib and Sotorasib (AMG510) resistant-KRAS-G12C secondary mutations, such as KRAS-G12C-Y96C and KRAS-G12C-H95Q. In addition, IHMT-RAF-128 showed excellent pharmacokinetic profile (PK), and the bioavailability in mice and rats were 63.9%, and 144.1%, respectively. Furthermore, IHMT-RAF-128 exhibited potent anti-tumor efficacy on xenograft mouse tumor models in a dose-dependent manner without any obvious toxicities. Together, these results support further investigation of IHMT-RAF-128 as a potential clinical drug candidate for the treatment of cancer patients with RAF or RAS mutations.
Financial Toxicity among Cancer-Survivors: A Conceptual Model Based on a Feedback Perspective
Authors: Scheidegger Alexander , Bernhardsgrütter Daniela , Kobleder Andrea , Müller Martin , Nestor Karen , Richle Ernst , Baum Eleonore
Published: December 2022

Purpose
Experiencing financial toxicity following a cancer diagnosis is a circular and complex process. We investigate the circular causal mechanisms that either reinforce or balance financial toxicity dynamics.
Methods
We conducted a literature review, expert interviews, a participatory modeling process and exploratory interviews with N = 11 adults with cancer living in Switzerland. We sampled participants purposively based on health-related and sociodemographic characteristics.
Results
We describe a conceptual model based on the triangulation of cancer survivor narratives, expert perspectives, and a literature review. This model distinguishes between the reinforcing and balancing feedback loops that drive the dynamics of financial toxicity. It includes the topics “Coping with Cancer and Employment”, “Coping with Limited Economic Resources” and “Maintaining Care Resources While Facing Economic Pressure.” For each topic, we identify a necessary condition for cancer survivors to avoid reinforcing financial toxicity.
Conclusions
The results allow us to reconstruct participant narratives regarding cancer-related financial toxicity. Based on comparison with scientific literature from Western Europe and North America, we hypothesize the validity of the model beyond the population covered by the sample. The results highlight the importance of screening for the risk of financial toxicity in the clinical context and individual risk and resource assessment in social counseling.
Implications for Cancer Survivors:
These results can raise cancer survivors’ awareness of risks related to financial toxicity and strengthen their resources for coping with financial burden successfully.
High Throughput Metabolomics In vitro Platform for The Identification of Hepatotoxicity Modes of Action
Authors: Ramirez-Hincapie Sabina , Birk Barbara , Ternes Philipp , Giri Varun , Haake Volker , Herold Michael , Zickgraf Franziska Maria , Verlohner Andreas , Huener Hans-Albrecht , Kamp Hennicke , Driemert Peter , Landsiedel Robert , Richling Elke , Funk-Weyer Dorothee , Ravenzwaay Bennard van
Published: December 2022

Cell-based metabolomics provides multiparametric physiologically relevant readouts that can be highly advantageous for improved, biologically based decision making in early stages of compound development. Here we present the development of a 96-well plate LC-MS-based targeted metabolomics screening platform for the classification of liver toxicity MoAs in HepG2 cells. Different parameters of the workflow (cell seeding density, passage number, cytotoxicity testing, sample preparation, metabolite extraction, analytical method, and data processing) were optimized and standardized to increase the efficiency of the testing platform. The applicability of the system was tested with seven substances known to be representative of three different liver toxicity MoAs (peroxisome proliferation, liver enzyme induction and liver enzyme inhibition). Multivariate and univariate analyses showed a dose response of the metabolic effects, a clear differentiation between liver toxicity MoAs and resulted in the identification of metabolite patterns specific for each MoA. Key metabolites indicative of both, general and mechanistic specific hepatotoxicity were identified. The method presented here offers a multiparametric, mechanistic-based and cost-effective hepatotoxicity screening that provides MoA classification and sheds light into the pathways involved in the toxicological mechanism. This assay can be implemented as a reliable compound screening platform for improved safety assessment in early compound development pipelines.
Effect of soil amendments on the sorption behaviour of atrazine in sandy loam soil
Authors: Khan Saifullah , Kumar Anup , Prasad Mahendra , Upadhyay Deepak , Mehta Brijesh K , P Shashikumara , Tamboli Pooja
Published: December 2022

The behaviour of pesticides applied during cultivation of crops is affected by usage of amendments like farm yard manure (FYM) and vermicompost (VC) during land preparation. Among pesticides, atrazine, a widely used herbicide in many crops, was analysed for its kinetics and sorption behaviour through the addition of FYM and VC in sandy loam soil. The pseudo-second order (PSO) model best fits kinetic results in the recommended dose of FYM and VC mixed soil. Atrazine was more sorbed onto VC mixed soil than FYM mixed soil during adsorption. Both FYM and VC (1, 1.5, and 2%) increased atrazine adsorption, but the effect varied with dosage and type of amendment. The Freundlich adsorption isotherm adequately explained atrazine adsorption in soil/soil+(FYM/VC) mixtures, and adsorption was highly nonlinear. The values of Gibb’s free energy change (ΔG) were negative for both adsorption and desorption, suggesting sorption was exothermic and spontaneous in nature. The results revealed that the application of amendments used by farmers interferes with the availability, mobility, and infiltration of atrazine in the soil. Therefore, the findings of this study suggest that amendments like FYM and VC can be effectively used to minimize the residual toxicity of atrazine treated ago-ecosystems in tropical and sub-tropical regions.
An inter-galactic magnetic field strength of ~ 4 x 10-17 G inferred with GRB 221009A
Authors: Xia Zi-Qing , Wang Yun , Yuan Qiang , Fan Yi-Zhong
Published: December 2022

The delayed GeV-TeV cascade emission from extragalactic TeV-PeV sources are regarded as an ideal probe of the inter-galactic magnetic fields. Recently, LHAASO has detected ~10 TeV emission of the extraordinary powerful GRB 221009A within ~2000 s after the burst. Here we report the detection of a ~400 GeV photon, without accompanying prominent low-energy emission, by Fermi-LAT in the direction of GRB 221009A with the time delay of 0.4 days. Such a hard spectrum can be generated from electromagnetic cascades initiated by early primary ~ 10 TeV photons in the intergalactic space. An inter-galactic magnetic field strength of BIGMF ~ 4 x 10-17 G, comparable to limits from TeV blazars, can naturally account for the arrival time of the ~400 GeV photon as well as the HAWC non-detection. Such a strength will be stringently tested by the upcoming CTA.
Association between Surgery for Odontoid Fractures in the Elderly and in-hospital Outcomes: Analysis from the American College of Surgeons Trauma Quality Improvement Program
Authors: Merali Zamir , Zhang Peng F. , Jaffe Rachael H. , Jaja Blessing N. R. , Harrington Erin M. , Malhotra Armaan K. , Smith Christopher W. , He Yingshi , Balas Michael , Jack Andrew S. , Fehlings Michael G. , Wilson Jefferson R. , Witiw Christopher D.
Published: December 2022

Odontoid fractures are increasingly prevalent in older adults and associated with high morbidity and mortality. Optimal management remains controversial. Our study aims to investigate the association between surgical management of odontoid fractures and in-hospital mortality in a multi-center geriatric cohort. We identified patients 65 years or older with C2 odontoid fractures from the Trauma Quality Improvement Program database. The primary study outcome was in-hospital mortality. Secondary outcomes were in-hospital complications and hospital length of stay. Generalized estimating equation models were used to compare outcomes between operative and non-operative cohorts. Among the 13218 eligible patients, 1100 (8.3%) were treated surgically. The risk of in-hospital mortality did not differ between surgical and non-surgical groups, after patient and hospital-level adjustment (OR: 0.94, 95%CI: 0.55–1.60). The risks of major complications and immobility-related complications were higher in the operative cohort (adjusted OR: 2.12, 95%CI: 1.53–2.94; and OR: 2.24, 95%CI: 1.38–3.63, respectively). Patients undergoing surgery had extended in-hospital length of stay compared to the non-operative group (9 days, IQR: 6–12days vs. 4 days, IQR: 3-7days). These findings were supported by secondary analyses that considered between-center differences in rates of surgery. Among geriatric patients with odontoid fractures surgical management was associated with similar in-hospital mortality, but higher in-hospital complication rates compared to non-operative management. Surgical management of geriatric patients with odontoid fractures requires careful patient selection and consideration of pre-existing comorbidities.
Placement of EVD in pediatric posterior fossa tumors: safe and efficient or old-fashioned? The Vienna experience
Authors: Hedrich Cora , Gojo Johannes , Azizi Amedeo , Peyrl Andreas , Slavc Irene , Winter Fabian , Czech Thomas , Dorfer Christian
Published: December 2022

Purpose The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity.
Methods This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022.
Results Of the 100 patients with posterior fossa tumors, 80patients (80%) had signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients the EVD was inserted at a mean of 2.25 days prior to the tumor resection, 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11 and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61+/-3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35+/-3.8 (range 0-16 days). EVD associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at six months after surgery was necessary in 13 patients (13%), including two VP-shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP-Shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p<0.001). In patients with metastatic disease 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p=0.001).
Conclusion The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.
Delivery of a tissue derived extracellular matrix gel modulates early fibro-adipogenic cell behavior and improves recovery following both acute and chronic atrophy muscle injury
Authors: Huynh Tai , Slavin Chris , Ahmadi Shahryar , Wolchok Jeffrey C.
Published: December 2022

In this study we examined the potential of muscle derived extracellular matrix (ECM) gel prepared from skeletal muscle as a treatment strategy for acute and chronic degenerative atrophy. We conducted experiments to evaluate the gel’s effectiveness in both a mouse hindlimb unloading (HU) model (disuse atrophy), and on a rabbit shoulder rotator cuff tear (RCT) model (diseased atrophy). In the HU mouse model, the gel enhanceddenovomuscle regeneration (4000% higher in centralized nuclei myofiber density) and muscle mass (22% heavier) in the tibialis anterior muscle compared to PBS group. The transcriptomic and proteomic analysis using mouse tissues revealed that the gel elicited adult myogenesis programme. In the RCT rabbit model, the gel enhanced muscle mass (19% heavier), average myofiber cross-sectional area (29% larger), and lowered fatty infiltration (72% less fat) in the supraspinatus muscle compared to repair only. The transcriptomic and proteomic analysis using rabbit tissues revealed that the gel enhanced recovery through promoting a pro-myogenic muscle environment while lessening adipogenesis. The findings suggested that gel injection had a positive effect on the treatment of muscle atrophy and the therapeutic effect of the ECM gel was in part via its impact on fibro-adipogenic progenitor cell behavior, a mechanistic finding that could be exploited for even greater impact.
The Role of Diversity on the Environmental Performance and Transparency
Authors: ÖZPARLAK Gerçek , GÜROL Burcu
Published: December 2022

Global warming and climate crisis are increasing their effects day by day. The Sustainable Development Goals (SDGs) put forward by the United Nations (UN) are the result of efforts to put sustainability on the agenda of the whole world. 17 goals serve the idea of a better world, not only environmentally but also socially. Even though the goals are seen as separate, all the goals are related to each other. While SDG 5 Gender Equality, and also SDG 10 Reduce Inequalities focus on eliminating gender-related disadvantages, it can also pave the way for disadvantaged groups to contribute in accordance with other goals with their different personal characteristics than men, by ensuring equal opportunities for the genders. For example, when women, who are more sensitive to environmental problems, take part in the decision-making bodies of companies, the environmental activity results of the enterprise may be more positive. To analyze this situation, we used 14-year data of 166 businesses traded in the US and Europe. We analyzed the diversity measures (board size-BS and women ratio on board-WOB ratio) and environmental performance results data and retested the results we reached. In this study, we focus on the E score and analyze the relationship in the short and long term, since the previous literature focused heavily on ESG scores and the results differed. The results show that there is a positive and meaningful relationship between BS and the ratio of WOB in the long run, although not in the short term.
Marginal abatement cost curves (MACCs) for assessing the role of market-based measures (MBMs) in enhancing the adoption of alternative marine fuels
Authors: Lagouvardou Sotiria , Lagemann Benjamin , Psaraftis Harilaos , Lindstad Elizabeth , Erikstad Stein Ove
Published: December 2022

Uncertainties on the global availability and affordability of alternative marine fuels are stalling the shipping sector’s decarbonization course. Several candidate measures are proposed at the International Maritime Organization, including market-based measures (MBMs), environmental policies like carbon taxes and emissions trading systems. Their implementation increases the cost of fossil fuel consumption and provides fiscal incentives towards greenhouse gas emissions reductions. MBMs can bridge the price gap between alternative and conventional fuels and generate revenues for funding the up-scaling of alternative fuels' production, storage and distribution facilities and, thus, enhance their availability. By estimating the fuels' implementation and operational costs and carbon abatement potential, this study develops their marginal abatement cost curves and estimates the optimal level of carbon pricing needed to render investments into alternative fuels cost-effective. The results can assist policymakers in establishing the fundamental factors and MBM design principles that can make MBMs a robust and effective decarbonization measure.
Predicting the Allowable Settlement of Reinforced Soil Foundations: A Laboratory Study
Authors: Buragadda Venkatesh , Orekanti Eswara Reddy
Published: December 2022

It is reported in the literature that the load-carrying capacity of the reinforced sand bed increases with increasing the footing settlement. However, the nature of settlement plays a critical role in shallow foundation designs due to the conditional allowable settlement of the footings. In this present study, laboratory model tests have been performed on a model jute geotextile reinforced sand bed under 1g condition. The associated scaling laws are adopted for the geometrical parameters of the model footing and reinforcements as proposed in the literature. On the other hand, a new approach has been developed for the model reinforcements for scaling down of geosynthetic materials under 1g condition to simulate the condition of geosynthetic reinforcement layers as in the field or Ng conditions. The test results revealed that based on the scaling factors the model footing can be allowed to settle according to the criteria of footing settlement and allowable reinforcement tensile strains. Finally, the suitable guidelines have also been developed as per the safety considerations in order to understand the effect of reinforcement layers on the improvement of soil bearing capacity ratio (BCR) up to a certain settlement ratio (s/D) of the footing.
Addiction to medical websites post COVID-19 pandemic: A predictor of Illness Anxiety Disorder among Arabian youth
Authors: Hamid Mohamed , Mohamed Nagwa , Rivera Rita M. , Carballea Denise , Hamza Eid Abo
Published: December 2022

Background
The coronavirus (COVID-19) pandemic has significantly impacted every region of the world. During these unprecedented times, individuals have been experiencing severe mental health issues concerning excessive internet usage.
Methods
This study examined he relationship between addiction to medical websites and behaviors related to Illness Anxiety Disorder among a population of Arabic university students. A sample consisting of N = 368 youths was examined.
Results
Statistical analysis was conducted in the form of bivariate linear regression, Z score, R2, t-test, ANOVA, mean and standard deviation. Results: The analysis results found a linear equation predicting illness anxiety among youths. The correlation between the addiction to medical websites and hypochondria was found as 0.69.
Conclusions
Findings supported the notion that addiction to medical websites significantly predicts hypochondria.
“I am not alone”. The experiences of young females with type 1 diabetes participating in eating disorders prevention groups. A qualitative feasibility study
Authors: Hage Trine Wiig , Nilsen Jan-Vegard , Karlsen Katrine M , Lyslid Martine H , Wennersberg Anne Louise , Wisting Line
Published: December 2022

Objective
The overall aim of the current study was to qualitatively explore the feasibility of eating disorder prevention groups.
Method
A generic qualitative focus group design was applied. 17 participants accepted the invitation to attend focus group interviews after completing the intervention. Five focus groups were conducted in total.
Results
The qualitative analysis generated one overarching theme, named the benefit of meeting peers with a lived experience of T1D and body image concerns, and four themes: the need for an integrated focus on diabetes, personal relevance, providing sufficient balance between structure and flexibility and enabling a different perspective.
Conclusion
Results show overall positive feedback regarding the content and structure of the intervention, and underline the importance of targeting preventive efforts to specific risk groups.
Graphene Nanoplatelet/Cellulose Acetate Composite Film with Simultaneously and Significantly Enhanced Antistatic, Thermal Dissipative and Mechanical Properties for Packaging
Authors: Gao Zijun , Li Yao , Huang Pei , Zou Rui , Li Yuanqing , Fu Shaoyun Y.
Published: December 2022

With the increased concern over environment protection, cellulose acetate (CA) has drawn great interests as an alternative for packaging material due to its biodegradability and abundant resources; whereas, the poor antistatic property and thermal conductivity restrict its application in packaging. In this work, we propose a simple but effective strategy to produce high performance graphene nanoplatelet (GNP)/CA composite films via the consecutive homogenization and solvent cast processes. Relying on the spontaneous absorption of CA during homogenization, the GNP/CA produced shows an excellent dispersibility in the N,N-Dimethylformamide (DMF) solution and much less structural defects compared with GNP alone. As a result, the composite film obtained shows simultaneously and significantly enhanced antistatic, heat dissipative and mechanical properties compared to the CA case. Specifically, the GNP/CA composite with the optimal formula produced has promising overall performances (namely, surface resistivity of 1.14×107 Ω/sq, in-plane thermal conductivity of 5.359 W · m-1 · K-1, out-of-plane thermal conductivity of 0.785 W · m-1 · K-1, and tensile strength of 37.1 MPa). Featured by its promising overall properties, simple production processes and biodegradability, the as-prepared GNP/CA composite film shows a great potential for application in packaging.
Regularizers to the Rescue: Fighting Overfitting in DeepLearning-based Side-channel Analysis
Authors: Rezaeezade Azade , Batina Lejla
Published: December 2022

Despite considerable achievements of deep learning-based side-channel analysis, overfitting represents a significant obstacle in finding optimized neural network models. This issue is not unique to the side-channel domain. Regularization techniques are popular solutions to overfitting and have long been used in various domains. At the same time, the works in the side-channel domain show sporadic utilization of regularization techniques. What is more, no systematic study investigates these techniques’ effectiveness. In this paper, we aim to investigate the regularization effectiveness by applying four powerful and easy-to-use regularization techniques to six combinations of datasets, leakage models, and deep-learning topologies. The investigated techniques are L1, L2, dropout, and early stopping. Our results show that while all these techniques can improve performance in many cases, L1 and L2 are the most effective. Finally, if training time matters, early stopping is the best technique to choose.
Investigating spatial and temporal trend of groundwater quality in relation to water balance components (A case study of Chaharmahal va Bakhtiari Province, Iran)
Authors: Zamani-Ahmadmahmoodi Rasool , Bayati Samira , Abdollahi Khodayar , Gharahi Nasrin , Isa-Abadi Ali Raeisi , Chamani Atefeh
Published: December 2022

One of the problems of water resources in Iran is excessive drop in groundwater level, in which Chaharmahal va Bakhtiari province, located in this country, is no exception․ In this study, the trend of spatial and temporal changes in groundwater quality and water balance and the relationship between them in this province were investigated. The WetSpass-M distribution model was used due to the capability of distribution models in simulating watershed hydrological processes. The results showed good accuracy of the model in simulating runoff and basal flow of the study basin. The trend of water quality changes was investigated by calculating the IRWQI index and preparing its zoning maps. For this purpose, 132 samples of well water in different areas of the study were prepared in 2007 to 2017. Spatial distribution maps showed that the groundwater quality in the north and northeast of the region was lower than in other parts. Also, groundwater quality had declined over time. In rangeland, groundwater quality was better and nitrate level was lower than in agriculture and buildup land uses. Also, the relationship between nitrate and drought with water quality was seen due to the similar color pattern in their zoning maps in the region. The correlation between groundwater quality parameters and water balance components also showed a weak correlation on an annual scale and a strong correlation between some parameters in some wells on a monthly scale.
Multi-Modal Fine-Grained Activity Recognition and Prediction in Assembly
Authors: Chen Haodong , Zendehdel Niloofar , Leu Ming C. , Yin Zhaozheng
Published: December 2022

Assembly activity recognition and prediction help to improve productivity, quality control, and safety measures in smart factories. This study aims to sense, recognize, and predict a worker's continuous fine-grained assembly activities in a manufacturing platform. We propose a two-stage multi-modal network for workers' fine-grained activity recognition by leveraging scene-level and temporal-level activity features. The first stage is a feature awareness block that learns scene-level features from red-green-blue (RGB) and hand skeleton frames. We use the transfer learning method in the first stage and compare three different pre-trained feature extraction models. Then, we transmit the feature information from the first stage to the second stage to learn the temporal-level features of activities. The second stage consists of the Recurrent Neural Network (RNN) layers and a final classifier. We compare the performance of two different RNNs in the second stage, including the Long Short-Term Memory (LSTM) and the Gated Recurrent Unit (GRU). The partial video observation method is used in the prediction of fine-grained activities. In the experiments using the trimmed activity videos, our model achieves an accuracy of > 99% on our dataset and > 98% on the public dataset UCF 101, outperforming the state-of-the-art models. The prediction model achieves an accuracy of > 97% in predicting activity labels using 50% of the onset activity video information. In the experiments using an untrimmed video with continuous assembly activities, we combine our recognition and prediction models and achieve an accuracy of > 91% in real time, surpassing the state-of-the-art models for the recognition of continuous assembly activities.
Detection of cytomegalovirus in bronchoalveolar lavage fluid from immunocompromised patients with pneumonitis by viral culture and DNA quantification
Authors: Berengua Carla , Miró E. , Gutiérrez C. , Sánchez M. , Mulero A. , Ramos P. , Cuerpo M. , Torrego A. , García-Cadenas I. , Pajares V. , Navarro F. , Martino R. , Rabella N.
Published: December 2022

Purpose
To compare the detection of human cytomegalovirus (HCMV) in bronchoalveolar lavage (BAL) fluid by viral culture and quantitative polymerase chain reaction (qPCR), and to establish a viral load threshold that can identify cases of HCMV replication indicative of pneumonitis. There is currently no universal viral load cut-off to differentiate between patients with and without pneumonitis, and the interpretation of qPCR results is challenging.
Methods
176 consecutive BAL samples from immunosuppressed hosts with signs and/or symptoms of respiratory infection were prospectively studied by viral culture and qPCR.
Results
Concordant results were obtained in 81.25% of the BAL samples. The rest (18.75%) were discordant, as only 34% of the qPCR-positive BAL samples were positive by culture. The median HCMV load was significantly higher in culture-positive than in culture-negative BAL samples (25,188 vs 890 copies/mL). HCMV was isolated in 100% of the BAL cultures with a viral load of > 4,500 copies/mL.
Conclusion
Availability of reference values for the HCMV load in BAL fluid facilitates the interpretation of qPCR results and clinical decision-making. We found that a negative PCR test was a quick and reliable way of ruling out HCMV pneumonitis, but a positive result did not always indicate clinically significant replication in the lung. However, an HCMV load in BAL fluid of > 4,500 copies/mL was always associated with the disease, whereas < 1,000 copies/mL rarely so. These data may be useful for centres without access to gold-standard techniques.
A Comprehensive Survey of Feature Selection Techniques based on Whale Optimization Algorithm
Authors: Ebrahimabadi Mohammad Amiri , Mansouri Najme
Published: December 2022

A large number of features is the main problem in big data, leading to the curse of dimensionality. Meanwhile, feature selection is suggested as a solution. The process of feature selection consists of adding relevant features to a neural model and eliminating irrelevant or redundant ones. The feature selection community has recently been drawn to swarm intelligence techniques due to their simplicity and potential global search capabilities. A straightforward overview of the newest research in the feature selection field is provided here using a nature-inspired metaheuristic method called Whale Optimization Algorithm (WOA). Research is expected to be presented in terms of various types of state-of-the-art methods and their advantages and disadvantages, encouraging researchers to investigate more advanced approaches. A discussion of possible limitations and issues for future research is included as well as guidance for practitioners on selecting appropriate methods for real-world situations.
Fabrication, characterization and adsorption investigation of Nano zinc oxide–sodium alginate beads for effective removal of chromium (VI) from aqueous solution
Authors: Hezma A. M. , Shaltout Walaa A. , Kabary Hoda A. , El-Bahy Gamal S. , Abdelrazzak Abdelrazek B.
Published: December 2022

Zinc oxide nanoparticles (ZnO-NPs) were prepared by modified wet chemical method while alginate-zinc oxide (Alg-ZnO) composite was synthesized by the interaction between the prepared zinc oxide nanoparticles and calcium alginate. The solid adsorbents were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and UV-Vis spectroscopy. Adsorption isotherms of chromium ions were investigated onto the prepared solid adsorbents with varying the initial concentration of Cr(VI) under different application conditions such as pH, contact time, adsorbent dosage, and temperature. Adsorption of Cr(VI) was investigated by different isotherm models like Langmuir, Freundlich, Temkin and Dubinin-Radushkevich models. Maximum adsorption capacities (31.09 and 34.63 mg/g) were achieved by ZnO-NPs and Alg-ZnO, respectively at 25 ℃. The results of isotherm models indicate the perfect applicability of Langmuir and Dubinin-Radushkevich models, revealing the dominance of monolayer and the physisorption of chromium ions onto the studied adsorbents.
Deepening Fiscal Decentralization as a Path to Fiscal Responsibility? A Comparison of the Czech Republic and Turkey
Authors: Babaoğlu Cenay , Sobotková Lucie , Sobotka Martin , Köktaş Murat Altuğ , Kulaç Onur
Published: December 2022

The article deals with the issue of fiscal decentralization in relation to compliance with fiscal discipline at the municipal level. The article evaluates the situation of selected Czech and Turkish cities. In the case of Czech cities, so-called statutory cities were selected, which, due to their size and budget, have a certain independence from the central government. In the case of Turkish cities, the largest ones were analyzed, which also have a high degree of autonomy due to their size. The unifying element of both samples is approximately similar financing conditions. In both cases, shared taxes are used, but they are in the hands of the central government, and the municipalities have no possibility to influence them. In the case of municipalities, they can receive subsidies from the central government. From the perspective of fiscal responsibility management, relations with the central government appear to be a stabilizing element. However, at the same time, strengthening revenues associated with local government could also support fiscal discipline. In particular, this possibility would be significant in the case of smaller municipalities when the share of local income in total income is increasing. Another option for discussion is the availability of debt financial instruments. In the case of Turkish cities, fiscal discipline is significantly correlated with external debt. Although Czech municipalities can easily access debt financial instruments, they cannot use foreign financing.
JEL Classification: C33, C35, H71, H72, H77
Stability and large time behavior for 2D Boussinesq system with horizontal dissipation and horizontal diffusion
Authors: Wan Yaqi , Chen Xiaoli , Chen Dongxiang
Published: December 2022

This paper is concerned with two dimensional Boussinesq equations involving the horizontal dissipation in the first component of the velocity and horizontal temperature diffusion. Due to the lack of vertical dissipation in the horizontal velocity component and full dissipation in the vertical velocity component, this problem becomes more challenging than that in [15]. When the spatial domain is Ω = T × R with T = [0, 1] being a 1D periodic box, we establish the stability and build the precise large-time behavior of perturbations near the hydrostatic equilibrium. We further prove that the oscillation parts of the velocity and the temperature only share the decay rate as (1 + t)− 1/2.
Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid Pigs
Authors: Li Mingzhou
Published: December 2022

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeepin situHi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omics data revealed the tissue-dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic rewiring of long-range promoter-enhancer contacts, which likely contribute to the dramatic phenotypic differences between the parental pig breeds. This study also provides definitive evidence of structured homolog pairing in the pig genome which could facilitate regulatory interactions between homologous chromosomes. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, and consequently phenotypic changes in mammals.
MAFLD in Obesity with Deteriorating Glucose Control
Authors: Forst Thomas , Botz Isabel , Berse Matthias , Voswinkel Stephan , Strempler Mares-Elaine , Baumann Sybille , Schultz Armin
Published: December 2022

Background: The incidence of metabolic dysfunction- associated fatty liver disease (MAFLD) is rising in parallel with increasing bodyweight and loss of glucose control, implicating a high risk of hepatic and extra-hepatic complications. Subjects / Methods: This longitudinal observational study analysed several indicators for MAFLD in 240 overweight subjects (body mass index (BMI) > 28 kg/m²) at 2 visits within in average 16 months. Subjects were categorised according to their insulin sensitivity (HOMAIR) and diabetic status. Methods: Liver fat and liver stiffness were measured with sonographic elastography (FibroScan®), and by calculation of Fatty Liver Index (FLI), and NAFLD Fibrosis Score (NFS). Results: Parameters indicative for liver steatosis, i.e., the controlled attenuation parameter (CAP) and the FLI, were significantly higher in the T2DM group compared to the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups (p<0.05). FLI values and the HOMAIRsignificantly correlated with sonographic liver fat content (CAP) (r=0.53, p<0.0001; r=0.34, p<0.001, respectively). An inverse correlation was observed between serum adiponectin levels and CAP (r=-0.20; p<0.019) and adiponectin levels and FLI (r=-0.37; p<0.0001). Over 16 months, fasting insulin levels and HOMAIRscore increased mainly driven by the group of obese subjects with T2DM. No significant change in liver fat or stiffness was observed that period. Conclusions: In subjects with a BMI ≥ 28kg/m², the prevalence of MAFLD increases in line with increasing insulin resistance and loss of glucose control. Despite some further deterioration in insulin sensitivity, liver fat content appeared relatively unchanged over 16 months.
Machine learning revealed inflammatory features and a novel risk score-based classification with appealing implications in discriminating the prognosis, immunotherapy and chemotherapy
Authors: Bai Weiyu , Bai Weiyu
Published: December 2022

Breast cancer is the most common and ranks the second cause of related cancer-related death in women. However, the relationship between inflammation-related gene signatures and the prognosis of breast cancer remains elusive. We constructed inflammation related gene features to evaluate the prognosis, immunotherapy, inflammatory response and chemotherapy of breast cancer patients, including 4073 breast cancer patients (TCGA: 1104, GEO: 2969).
● Through univariate Cox regression, LASSO, stepwise regression, and multiple Cox regression analyses, we found that the signatures of inflammatory genes (including 12 genes) can be used to classify breast cancer patients. Patients in the higher risk score group had a poorer prognosis, often accompanied by a higher abundance of macrophages and a lower abundance of lymphocytes, suggesting that inflammation was present in high-risk individuals.
● Tumor mutational burden (TMB) and drug sensitivity analysis showed that PD 0332991, ROSCOVITINE has a higher drug sensitivity to the treatment of low-risk inflammatory breast cancer, while it has a higher drug sensitivity to high-risk patients than carlumide and imatinib.
● Based on risk scores and clinical data, we use training sets and test sets to build nomographs that can be used to calculate patient survival.
Our study provides not only insights into the identification of breast cancer patients with poor prognoses, but also treatment strategiesfor breast cancer patients.
The Peptidyl-Prolyl cis-trans Isomerase, Pin1, Associates with Protein Kinase C θ (PKCθ) via a Critical Phospho-Thr-Pro Motif in the V3 Regulatory Domain
Authors: Anto Nikhil Ponnoor , Muraleedharan Amitha , Nath Pulak Ranjan , Sun Zuoming , Keasar Chen , Livneh Etta , Braiman Alex , Altman Amnon , Kong Kok-Fai , Isakov Noah
Published: December 2022

Protein kinase C-θ (PKCθ) is a member of the novel PKC subfamily known for its selective and predominant expression in T lymphocytes where it regulates essential functions required for T cell activation and proliferation. Our previous studies provided a mechanistic explanation for the recruitment of PKCθ to the center of the immunological synapse (IS) by demonstrating that a proline-rich (PR) motif within the V3 region in the regulatory domain of PKCθ is necessary and sufficient for PKCθ IS localization and function. Herein, we highlight the importance of Thr335-Pro residue in the PR motif, the phosphorylation of which is key in the activation of PKCθ and its subsequent IS localization. We demonstrate that the phospho-Thr335-Pro motif serves as a putative binding site for the peptidyl-prolyl cis-trans isomerase (PPIase), Pin1, an enzyme that specifically recognizes peptide bonds at phospho-Ser/Thr-Pro motifs. Binding assays revealed that mutagenesis of PKCθ-Thr335-to-Ala abolished the ability of PKCθ to interact with Pin1, while Thr335 replacement by a Glu phosphomimetic, restored PKCθ binding to Pin1, suggesting that Pin1-PKCθ association is contingent upon the phosphorylation of the PKCθ-Thr335-Pro motif. Similarly, the Pin1 mutant, R17A, failed to associate with PKCθ, suggesting that the integrity of the Pin1 N-terminal WW domain is a requisite for Pin1-PKCθ interaction. In silico docking studies underpinned the role of critical residues in the Pin1-WW domain and the PKCθ phospho-Thr335-Pro motif, to form a stable interaction between Pin1 and PKCθ. Furthermore, TCR crosslinking in human Jurkat T cells and C57BL/6J mouse-derived splenic T cells promoted a rapid and transient formation of Pin1-PKCθ complexes, which followed a T cell activation-dependent temporal kinetic, suggesting a role for Pin1 in PKCθ-dependent early activation events in TCR-triggered T cells. PPIases that belong to other subfamilies, i.e., cyclophilin A or FK506-binding protein, failed to associate with PKCθ, indicating the specificity of the Pin1-PKCθ association. Fluorescent cell staining and imaging analyses demonstrated that TCR/CD3 triggering promotes the colocalization of PKCθ and Pin1 at the cell membrane. Furthermore, interaction of influenza hemagglutinin peptide (HA307–319)-specific T cells with antigen-fed antigen presenting cells (APCs) led to colocalization of PKCθ and Pin1 at the center of the IS. Together, we point to an uncovered function for the Thr335-Pro motif within the PKCθ-V3 regulatory domain to serve as a priming site for its activation upon phosphorylation and highlight its tenability to serve as a regulatory site for the Pin1 cis-trans isomerase.
The inert pair effect on the heavy noble gases: New insights from radon tetroxide.
Authors: Bandeira Nuno , Marçalo Joaquim
Published: December 2022

A quantum chemical survey of radon and xenon tetroxides (NgO4, Ng = Xe,Rn) is reported herein. The intermediate species that will form in their explosive decomposition back to their elemental states (Ng and O2) were also studied and their energetics compared. While Td symmetric RnO4 is a minimum energy structure, its standard enthalpy of formation is 88.6 kJ mol− 1 higher than for XeO4. The reason for this higher instability lies in what is known as the inert pair effect. This work adds to what is established wisdom in inorganic chemistry textbooks, a feature of the heavy elements of groups 13–15, extending it to include group 18.
The impact of indirect notification of a cancer diagnosis and a risk model based on it to predict the prognosis of postoperative stage T3 esophageal cancer patients
Authors: Cheng Yalin , Yu Minhao , Zhang Renfei , Long Zhiquan
Published: December 2022

Chinese doctors are required to inform patients’ direct relatives of a cancer diagnosis rather than the patients themselves. The disease may be hidden from patients by their family members, which could result in severe outcomes. We selected postoperative T3 esophageal cancer (EsC) patients hospitalized from June 2015 to December 2016 as research subjects. The patients were divided into a direct-notification group and an indirect-notification group. Several variables were used to evaluate both groups’ 36-month progress-free survival (PFS). Statistically significant results based on univariate analysis were incorporated into a Cox regression analysis. A risk prediction model of prognosis based on the risk score was established, which was assessed using the area under the curve (AUC) of the receiver operating characteristic curve. Internal validation was performed using bootstrapping. Seventy-two patients were enrolled in the study. Cox multivariate regression analysis revealed that late stage, poor pathological differentiation, and indirect notification were independent worse risk factors for postoperative T3 stage EsC patients at 36-month PFS (hazard ratio (HR) = 1.829, 95% confidence interval (CI): 1.027–3.258, P = 0.040; HR = 0.457, 95% CI: 0.259–0.805, P = 0.007; HR = 1.993, 95% CI: 1.117–3.556, P = 0.020, respectively). The risk score was calculated as follows: risk score = 0.690 × cancer notification (indirect = 1, direct = 0) + 0.604 × stage (IIIB = 1, IIA + IIB = 0) – 0.784 × pathological differentiation (moderately + well = 1, poorly = 0). The AUC of the model that included the type of notification was 0.727 (95% CI: 0.606–0.848), with a sensitivity of 70.0% and specificity of 75.0%, and the stability was better through internal verification. Indirect notification of a cancer diagnosis was an important negative predictor of postoperative EsC patients' PFS. The model that combined stage, pathological differentiation, and the type of notification of a cancer diagnosis displayed good accuracy and internal stability in the prediction of risk for cancer progression.
CONTROL OF DYNAMIC TRIM FOR PLANING VESSELS WITH INTERCEPTORS IN TERMS OF COMFORT AND MINIMUM DRAG
Authors:   Faculty of Maritime, Recep Tayyip Erdogan University, Sahin Omer Sinan , Kahramanoglu Emre ,   Faculty of Naval Architecture and Maritime, Izmir Katip Celebi University, Cakici Ferdi ,   Naval Architecture and Maritime Faculty, Yildiz Technical University, Pesman Emre ,   Faculty of Marine Sciences, Karadeniz Technical University
Published: December 2022

Nowadays, interceptors are often used to decrease total resistance and enhance comfort by reducing dynamic trim for high-speed planing vessels. They can be controlled manually as well as automatically by using a suitable closed-loop control system. Thus, in the present study, an automatically controllable system is presented to minimize the total resistance by reducing the dynamic trim in calm water. To reach this aim, a mathematical model which can represent the 2 degree of freedom vertical motion of a prismatic planing vessel is presented. The coefficients used in the model are calculated by using the Savitsky method. The standard dynamic trim angle and the optimum ones in terms of resistance are calculated by using the same method. For control action, a linear full state feedback control strategy (linear quadratic regulator) is applied, and instantaneous blade heights are found considering the change in forward speed. Therefore, the control-oriented model is able to change the blade height to reach the optimum trim angle in terms of the total resistance of the vessel for different forward speeds and speed profiles. The results show that the designed linear quadratic regulator control strategy is successful for reference trim tracking problems.