bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive-Toxicity-Related Endpoints in C. elegans Are Consistent with Reduced Concern for Dimethylarsinic Acid Exposure Relative to Inorganic Arsenic
Authors: Camacho Jessica A. , Welch Bonnie , Sprando Robert L. , Hunt Piper R.
Published: April 2023

Exposures to arsenic and mercury are known to pose significant threats to human health; however, the effects specific to organic vs. inorganic forms are not fully understood. Caenorhabditis elegans’ (C. elegans) transparent cuticle, along with the conservation of key genetic pathways regulating developmental and reproductive toxicology (DART)-related processes such as germ stem cell renewal and differentiation, meiosis, and embryonic tissue differentiation and growth, support this model’s potential to address the need for quicker and more dependable testing methods for DART hazard identification. Organic and inorganic forms of mercury and arsenic had different effects on reproductive-related endpoints in C. elegans, with methylmercury (meHgCl) having effects at lower concentrations than mercury chloride (HgCl2), and sodium arsenite (NaAsO2) having effects at lower concentrations than dimethylarsinic acid (DMA). Progeny to adult ratio changes and germline apoptosis were seen at concentrations that also affected gravid adult gross morphology. For both forms of arsenic tested, germline histone regulation was altered at concentrations below those that affected progeny/adult ratios, while concentrations for these two endpoints were similar for the mercury compounds. These C. elegans findings are consistent with corresponding mammalian data, where available, suggesting that small animal model test systems may help to fill critical data gaps by contributing to weight of evidence assessments.
Effect of Size, Shape and Surface Functionalization on the Antibacterial Activity of Silver Nanoparticles
Authors: Menichetti Arianna , Mavridi-Printezi Alexandra , Mordini Dario , Montalti Marco
Published: April 2023

Silver nanoparticles (AgNPs) are the most investigated antibacterial agents against multidrug resistant (MDR) pathogens. They can lead to cellular death by means of different mechanisms, damaging several cell compartments, from the external membrane, to enzymes, DNA and proteins; this simultaneous attack amplifies the toxic effect on bacteria with respect to traditional antibiotics. The effectiveness of AgNPs against MDR bacteria is strongly correlated with their chemical and morphological properties, which influence the pathways involved in cellular damage. In this review, AgNPs’ size, shape and modification by functional groups or other materials are reported, both to investigate the different synthetic pathways correlated with nanoparticles’ modifications and to evaluate the related effect on their antibacterial activity. Indeed, understanding the synthetic conditions for obtaining performing antibacterial AgNPs could help to tailor new and improved silver-based agents to combat multidrug resistance.
Fabrication of Black Silicon Microneedle Arrays for High Drug Loading
Authors: Cheng Wei , Wang Xue , Zou Shuai , Ni Mengfei , Lu Zheng , Dai Longfei , Su Jiandong , Yang Kai , Su Xiaodong
Published: April 2023

Silicon microneedle (Si-MN) systems are a promising strategy for transdermal drug delivery due to their minimal invasiveness and ease of processing and application. Traditional Si-MN arrays are usually fabricated by using micro-electro-mechanical system (MEMS) processes, which are expensive and not suitable for large-scale manufacturing and applications. In addition, Si-MNs have a smooth surface, making it difficult for them to achieve high-dose drug delivery. Herein, we demonstrate a solid strategy to prepare a novel black silicon microneedle (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The proposed strategy consists of a simple fabrication of plain Si-MNs and a subsequent fabrication of black silicon nanowires. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching. The nanowire structures were then prepared on the surfaces of the plain Si-MNs to form the BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag+ and HF concentrations during Ag nanoparticle deposition and [HF/(HF + H2O2)] ratio during Ag-catalyzed chemical etching, on the morphology and properties of the BSi-MNs were investigated in detail. The results show that the final prepared BSi-MN patches exhibit an excellent drug loading capability, more than twice that of plain Si-MN patches with the same area, while maintaining comparable mechanical properties for practical skin piercing applications. Moreover, the BSi-MNs exhibit a certain antimicrobial activity that is expected to prevent bacterial growth and disinfect the affected area when applied to the skin.
Person-Centered Study of Cognitive Ability Dimensions Using Latent Profile Analysis
Authors: Conte Jeffrey M. , Harmata Rebecca K.
Published: April 2023

A number of researchers have called for additional investigations into cognitive ability and intelligence in recent years. This paper utilized a person-centered approach, multiple cognitive ability dimensions, and latent profile analysis to investigate multivariate relationships among cognitive ability dimensions in a sample of 1681 Army recruits. Six cognitive ability dimensions were assessed via the Armed Services Vocational Aptitude Battery. Performance measures were obtained from supervisor ratings of Effort, Discipline, and Peer Leadership. Using latent profile analysis, the results identified five distinct cognitive profiles or classes, which differed significantly across the three types of supervisor ratings.
Battery Parameter Analysis through Electrochemical Impedance Spectroscopy at Different State of Charge Levels
Authors: Wu Yuchao , Sundaresan Sneha , Balasingam Balakumar
Published: April 2023

This paper presents a systematic approach to extract electrical equivalent circuit model (ECM) parameters of the Li-ion battery (LIB) based on electrochemical impedance spectroscopy (EIS). Particularly, the proposed approach is suitable to practical applications where the measurement noise can be significant, resulting in a low signal-to-noise ratio. Given the EIS measurements, the proposed approach can be used to obtain the ECM parameters of a battery. Then, a time domain approach is employed to validate the accuracy of estimated ECM parameters. In order to investigate whether the ECM parameters vary as the battery’s state of charge (SOC) changes, the EIS experiment was repeated at nine different SOCs. The experimental results show that the proposed approach is consistent in estimating the ECM parameters. It is found that the battery parameters, such as internal resistance, capacitance and inductance, remain the same for practical SOC ranges starting from 20% until 90%. The ECM parameters saw a significant change at low SOC levels. Furthermore, the experimental data show that the resistive components estimated in the frequency domain are very close to the internal resistance estimated in the time domain. The proposed approach was applied to eight different battery cells consisting of two different manufacturers and produced consistent results.
Energy-Efficient Audio Processing at the Edge for Biologging Applications
Authors: Miquel Jonathan , Latorre Laurent , Chamaillé-Jammes Simon
Published: April 2023

Biologging refers to the use of animal-borne recording devices to study wildlife behavior. In the case of audio recording, such devices generate large amounts of data over several months, and thus require some level of processing automation for the raw data collected. Academics have widely adopted offline deep-learning-classification algorithms to extract meaningful information from large datasets, mainly using time-frequency signal representations such as spectrograms. Because of the high deployment costs of animal-borne devices, the autonomy/weight ratio remains by far the fundamental concern. Basically, power consumption is addressed using onboard mass storage (no wireless transmission), yet the energy cost associated with data storage activity is far from negligible. In this paper, we evaluate various strategies to reduce the amount of stored data, making the fair assumption that audio will be categorized using a deep-learning classifier at some point of the process. This assumption opens up several scenarios, from straightforward raw audio storage paired with further offline classification on one side, to a fully embedded AI engine on the other side, with embedded audio compression or feature extraction in between. This paper investigates three approaches focusing on data-dimension reduction: (i) traditional inline audio compression, namely ADPCM and MP3, (ii) full deep-learning classification at the edge, and (iii) embedded pre-processing that only computes and stores spectrograms for later offline classification. We characterized each approach in terms of total (sensor + CPU + mass-storage) edge power consumption (i.e., recorder autonomy) and classification accuracy. Our results demonstrate that ADPCM encoding brings 17.6% energy savings compared to the baseline system (i.e., uncompressed raw audio samples). Using such compressed data, a state-of-the-art spectrogram-based classification model still achieves 91.25% accuracy on open speech datasets. Performing inline data-preparation can significantly reduce the amount of stored data allowing for a 19.8% energy saving compared to the baseline system, while still achieving 89% accuracy during classification. These results show that while massive data reduction can be achieved through the use of inline computation of spectrograms, it translates to little benefit on device autonomy when compared to ADPCM encoding, with the added downside of losing original audio information.
Marine Plastic Drift from the Mekong River to Southeast Asia
Authors: Nguyen Dung M. , Hole Lars R. , Breivik Øyvind , Nguyen Thuy B. , Pham Ngoc Kh.
Published: April 2023

Southeast Asia is the world’s most polluted area in terms of marine plastics. The Mekong River is one of the largest rivers in the area, and ranked as somewhere between the 8th- and 11th-biggest contributor to plastics in the world’s oceans. Here, we investigate how microplastics drift from the Mekong river to Southeast Asia, and which coastlines are most exposed. We identify potential factors (wind drift, rivers, vertical mixing and sinking rates) that affect plastic drift in the region using the OpenDrift model with realistic wind and ocean currents for simulations between three months (summer and winter) and 15 months. We find that the seasonal drift is influenced by the monsoon systems and that most of the plastics strand in the Philippines and Indonesia. In addition, the role of wind drift is significant in strong winds. Vertical mixing and sinking rates are unknowns that affect the relative importance of wind drift (near the surface) and ocean currents. Simulations with different terminal velocities show that, unsurprisingly, the higher the terminal velocities are, the closer they deposit to the source. In light of the large uncertainties in sinking rates, we find that the plastic distribution has large uncertainties, but is clearly seasonal and influenced by wind, vertical mixing, river discharge and sinking rates. The Philippines and Indonesia are found to have the coastlines that are most exposed to plastic pollution from the Mekong river. This study shows that simulations of marine plastic drift are very variable, depending on many factors and assumptions. However, it provides more detailed information on marine plastic pollution in Southeast Asia, and hopefully helps authorities take more practical actions.
Visibility Performance Assessment: Simulation of a Digital Shadow in a Port
Authors: Bergeron Erik , Audy Jean-François , Forget Pascal
Published: April 2023

The growth of goods transported by ship affects the entire maritime industry, which is central to the global supply chain. Faced with an increased pressure from the industry, ports need greater visibility on the flow of goods and logistics operations. To tackle this challenge, improvement opportunities as well as weaknesses must be identified in order to define an efficient data acquisition strategy that will allow port authorities to enhance their current visibility within their port ecosystem. This article presents the simulation of a digital shadow based on a Canadian port case study. The study uses the simulation of a digital shadow to diagnose a Canadian port authority’s current visibility, with an accent on data accuracy, in order to identify improvement opportunities aimed at overcoming weaknesses identified in a current practice scenario and then compare the performance of the current system with said improvements in a second scenario. To our knowledge, this is the first simulation study on visibility performance assessment in a port’s digital shadow.
Multilevel Inverse Patchmatch Network with Local and Global Refinement for Underwater Stereo Matching
Authors: Leng Jiaqi , Lv Qingxuan , Zhang Shu , Rao Yuan , Liu Yimei , Fan Hao
Published: April 2023

Vision-based underwater autonomous systems play a significant role in marine exploration. Stereo matching is one of the most popular applications for vision-based underwater autonomous systems, which recovers the geometric information of underwater scenes via stereo disparity estimation. While stereo matching in the air has achieved great progress with the development of neural networks, it generalizes poorly to the underwater scenario due to the challenging underwater degradation. In this paper, we propose a novel Multilevel Inverse Patchmatch Network (MIPNet) to iteratively model pair-wise correlations under underwater degradation and estimate stereo disparity with both local and global refinements. Specifically, we first utilized the inverse Patchmatch module in a novel multilevel pyramid structure to recover the detailed stereo disparity from the input stereo images. Secondly, we introduced a powerful Attentional Feature Fusion module to model pair-wise correlations with global context, ensuring high-quality stereo disparity estimation for both in-air and underwater scenarios. We evaluate the proposed method on the popular real-world ETH3D benchmark, and the highly competitive performance against the popular baselines demonstrates the effectiveness of the proposed method. Moreover, with its superior performance on our real-world underwater dataset, e.g., our method outperforms the popular baseline RAFT-Stereo by 27.1%, we show the good generalization ability of our method to underwater scenarios. We finally discuss the potential challenges for underwater stereo matching via our experiments on the impact of water.
Modeling Impact Load on a Vertical Cylinder in Dam-Break Flows
Authors: Mu Di , Chen Lifen , Ning Dezhi
Published: April 2023

A three-dimensional dam-break flow interacting with a vertical circular and square cylinder is studied in this paper using computational fluid dynamics simulations based on OpenFOAM. This resembles closely a tsunami wave and greenwater flow acting on coastal or on-deck structures, which are of relevance and importance to coastal protections and offshore operations, respectively. The numerical model is verified by comparing with published experimental measurements and is extended to investigate the effects of the structural geometry and the impacting angle β (i.e., the angle between the water front and cylinders) on the total impact load and the surrounding flow field. It is found that the impact event experiences two distinct stages characterized by a constant flow velocity and a negative flow acceleration, respectively. In addition, the total force on a square cylinder is nearly twice that of a circular cylinder although the impacting area is the same. The longitudinal and transverse forces are found to decrease and increase with the impacting angle, respectively. A close interrogation of the surrounding flow field via flow visualization suggests that the way the flow deflected from the cylinder surfaces plays an important role in determining the pressure field and thus the total force behaviors.
Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress
Authors: Liu Yijun , Mai Biyi , Li Zhiyun , Feng Xingqin , Chen Yunlan , Lin Lijing , Xia Qiuyu
Published: April 2023

Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. The results showed that GLPs consisted of D-glucose, D-galactose, and seven other monosaccharides. The end of the sugar chain had β-D-Glc and β-D-Gal configurations. The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the β-D-Gal configuration, while GLP4 and GLP6 had the β-D-Glc configuration. The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation.
A Gene from Ganoderma lucidum with Similarity to nmrA of Filamentous Ascomycetes Contributes to Regulating AreA
Authors: Liu He , Qiao Jinjin , Shangguan Jiaolei , Guo Xiaoyu , Xing Zhenzhen , Zhou Xiaolin , Zhao Mingwen , Zhu Jing
Published: April 2023

Fungal AreA is a key nitrogen metabolism transcription factor in nitrogen metabolism repression (NMR). Studies have shown that there are different ways to regulate AreA activity in yeast and filamentous ascomycetes, but in Basidiomycota, how AreA is regulated is unknown. Here, a gene from Ganoderma lucidum with similarity to nmrA of filamentous ascomycetes was identified. The NmrA interacted with the C-terminal of AreA according to yeast two-hybrid assay. In order to determine the effect of NmrA on the AreA, 2 nmrA silenced strains of G. lucidum, with silencing efficiencies of 76% and 78%, were constructed using an RNA interference method. Silencing nmrA resulted in a decreased content of AreA. The content of AreA in nmrAi-3 and nmrAi-48 decreased by approximately 68% and 60%, respectively, compared with that in the WT in the ammonium condition. Under the nitrate culture condition, silencing nmrA resulted in a 40% decrease compared with the WT. Silencing nmrA also reduced the stability of the AreA protein. When the mycelia were treated with cycloheximide for 6 h, the AreA protein was almost undetectable in the nmrA silenced strains, while there was still approximately 80% of the AreA protein in the WT strains. In addition, under the nitrate culture, the content of AreA protein in the nuclei of the WT strains was significantly increased compared with that under the ammonium condition. However, when nmrA was silenced, the content of the AreA protein in the nuclei did not change compared with the WT. Compared with the WT, the expression of the glutamine synthetase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 94% and 88%, respectively, under the ammonium condition, while the expression level of the nitrate reductase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 100% and 93%, respectively, under the nitrate condition. Finally, silencing nmrA inhibited mycelial growth and increased ganoderic acid biosynthesis. Our findings are the first to reveal that a gene from G. lucidum with similarity to the nmrA of filamentous ascomycetes contributes to regulating AreA, which provides new insight into how AreA is regulated in Basidiomycota.
Motorist’s Vestibular Disorientation Syndrome (MVDS)—Proposed Diagnostic Criteria
Authors: Pawar Vishal , Ashraf Hanaan , Dorsala Srinivas , Mary Preethy , Hameed Nazrin , H Divya Nair , Adatia Sweta Prakash , Raj Leya , Ananthu V. R. , Shouka M.
Published: April 2023

Motorist’s vestibular disorientation syndrome (MVDS) is a disorder in which patients experience dizziness while driving. MVDS is under-reported in the literature, and in clinical practice, it often goes unrecognized. We identified clinical characteristics of patients with MVDS using data from 24 patients who faced difficulties while driving and were diagnosed with MVDS. Their symptoms, duration of illness, precipitating factors, co-morbidities, history of other neuro-otological disorders, severity of symptoms, and associated anxiety and depression were reviewed. Ocular motor movements were recorded using video-nystagmography. Patients with vestibular disorders that can cause similar symptoms while driving were excluded. The mean age of the patients was 45.7 ± 8.7 years, and most were professional drivers (90.5%). The duration of the illness ranged from eight days to ten years. Most patients presented with disorientation (79.2%) exclusively while driving. The most common triggers for symptoms were higher speeds, i.e., >80 km/h (66.7%), multi-lane roads (58.3%), bends and turns (50%), and looking at other vehicles or signals while driving (41.7%). A history of migraines was reported in 62.5% of the patients, and motion sickness was reported in 50% of the patients. Anxiety was reported in 34.3% of patients, and 15.7% had depression. The video-nystagmography did not show any specific abnormalities. Patients responded to drugs used in prophylactic treatments for migraines such as Amitriptyline, Venlafaxine, Bisoprolol, and Magnesium, and to Pregabalin and Gabapentin. Based on these findings, a classification system and a diagnostic criterion for MVDS were proposed.
Robotic Single-Site Radical Hysterectomy for Early Cervical Cancer: A Single Center Experience of 5 Years
Authors: Song Changho , Jang Tae-Kyu , Kong Soomin , Kang Heeju , Kwon Sang-Hoon , Cho Chi-Heum
Published: April 2023

Background: The mainstay of treatment for early-stage cervical cancer is surgery; we present a 5-year experience of robotic single-site radical hysterectomy (RSRH) focused on surgical and oncologic outcomes. Methods: This retrospective study included 44 cases of RSRH performed in patients with early-stage cervical cancer. Results: The median follow-up period for the 44 patients was 34 months. The mean total operation time was 156.07 ± 31.77 min, while mean console time was 95.81 ± 24.95 min. Two cases had complications, which required surgical management, while four cases (9.1%) exhibited recurrence. The disease-free survival rate at 5 years was 90.9%. The sub-division analysis showed that Stage Ia2 and stage Ib1 patient sub-group showed better DFS than that of the stage Ib2 patient sub-group. The learning curve analysis showed that the CUSUM-T initially peaks at the sixth case then gradually decreases before rising and peaking at the 24th case. After 24th case, the CUSUM-T gradually decreases and reaches zero. Conclusion: The surgical outcomes of RSRH for early-stage cervical cancer treatment were safe and acceptable. However, RSRH could be considered carefully only in well-selected patient groups. Large-scale prospective studies are necessary in the future to validate the results.
The Impact of Venous Invasion on the Postoperative Recurrence of pT1–3N0cM0 Gastric Cancer
Authors: Imai Yasuo , Kurata Yoshihiro , Ichinose Masanori
Published: April 2023

The impact of venous invasion (VI) on postoperative recurrence in pathological (p)T1–3N0 clinical (c)M0 gastric cancer (GC) remains unclear. We investigated the association of VI grade with prognosis in 94 (78 stage I and 16 stage IIA) patients. VI was graded during pathological examinations based on the number of VIs per glass slide as follows: v0, 0; v1, 1–3; v2, 4–6; and v3, ≥7. Filling-type invasion in veins with a minor axis of ≥1 mm increased VI grade by 1. Four (4.3%) patients experienced recurrence. Recurrence increased with pT (pT1, 0.0%; pT2, 11.1%; pT3, 18.8%) and VI grade (v0, 0.0%; v1, 3.7%, v2, 14.3%; and v3, 40.0%). Recurrence was significantly more frequent in pT3 than pT1 and in v2 + v3 than v0 (p = 0.006 and 0.005, respectively). Kaplan–Meier curve analyses demonstrated a significant decrease in recurrence-free survival according to pT (p = 0.0021) and VI grade (p < 0.0001). Multivariate Cox analysis revealed a significant association of VI grade with recurrence (p = 0.049). These results suggest that VI grade is a potential recurrence predictor for pT1–3N0cM0 GC. No recurrence can be expected in cases with pT1 or VI grade v0. Adjuvant therapy might be considered for pT3 or VI grade v2 + v3.
Syncope—Do We Need AI?
Authors: Olshansky Brian , Gebska Milena A. , Johnston Samuel L.
Published: April 2023

Syncope is a form of transient loss of consciousness (TLOC) resulting from cerebral hypoperfusion and is characterized by rapid onset, short duration and spontaneous complete recovery [...]
Laboratory and Clinical Settings of Heavy/Light Chain (HLC) Assays in the Management of Monoclonal Gammopathies and Multiple Myeloma
Authors: Napodano Cecilia , Ioannilli Laura , Basile Valerio , Gulli Francesca , Carnazzo Valeria , Pignalosa Stefano , Di Biase Luigi , Cavaleri Erica , Racco Cosimo , Equitani Francesco , Marino Mariapaola , Basile Umberto
Published: April 2023

The antibody-related immune response is mediated by immunoglobulins (Igs), soluble circulating glycoproteins produced by activated B cells that, upon the recognition of specific epitopes on pathogen surfaces, activate, proliferate, and differentiate into antibody-secreting plasma cells. Although the antibodies are effectors of the humoral immune adaptive response, their overproduction in response to a dysregulated proliferation of clonal plasma cell production in tumoral conditions (i.e., multiple myeloma), enriches the serum and urinary matrices, assuming the crucial role of biomarkers. Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the expansion and accumulation of clonally activated plasma cells in bone marrow, determining the release of high amounts of monoclonal component (MC) that can be detected as intact immunoglobulin (Ig), immunoglobulin fragments, or free light chains (FLCs). The importance of detecting biomarkers for the diagnosis, monitoring, and prognosis of diseases is highlighted by the international guidelines that recommend specific assays for the analysis of intact Igs and FLC. Moreover, a developed assay called Hevylite® allows for the quantification of immunoglobulins that are both involved (iHLC) and not involved (uHLC) in the tumor process; this is a fundamental aspect of following up the patient’s workup and evaluating the progression of disease, together with the treatments response. We here summarize the major points of the complex scenario involving monoclonal gammopathies and MM clinical management in view of advantages derived for the use of Hevylite®.
Three Layers of Personalized Medicine in the Use of Sirolimus and Its Derivatives for the Treatment of Cancer
Authors: Delgado Andres , Enkemann Steven
Published: April 2023

Rapamycin and its derivatives are mTOR inhibitors which are FDA-approved for use as immunosuppressants and chemotherapeutic agents. These agents are currently approved to treat renal cell carcinomas, soft tissue sarcomas, and other rare tumors. As tumor treatment paradigms are moving away from organ-based drug selection and moving towards tumor characteristics for individualized treatment it is important to identify as many properties as possible that impact the efficacy of the rapalogues. A review of the current literature was conducted to identify enzymes involved in the metabolism of Sirolimus, Everolimus, Ridaforolimus, and Temsirolimus along with characteristics of tumors that predict the efficacy of these agents. This review also sought to establish whether the genetic characteristics of the patient might influence the activity of the rapalogues or lead to side effects from these agents. Current evidence suggests that tumors with mutations in the mTOR signal transduction pathway are sensitive to rapalogue treatment; the rapalogues are metabolized by cytochromes such as CYP3A4, CYP3A5, and CYP2C8 and transported by ABC transporters that are known to vary in activity in individuals; and that tumors can express these transporters and detoxifying enzymes. This results in three levels of genetic analysis that could impact the effectiveness of the mTOR inhibitors.
Personalized Management for Heart Failure with Preserved Ejection Fraction
Authors: Lin Chang-Yi , Sung Heng-You , Chen Ying-Ju , Yeh Hung-I. , Hou Charles Jia-Yin , Tsai Cheng-Ting , Hung Chung-Lieh
Published: April 2023

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying mechanisms and comorbidities that leads to a variety of clinical phenotypes. The identification and characterization of these phenotypes are essential for better understanding the precise pathophysiology of HFpEF, identifying appropriate treatment strategies, and improving patient outcomes. Despite accumulating data showing the potentiality of artificial intelligence (AI)-based phenotyping using clinical, biomarker, and imaging information from multiple dimensions in HFpEF management, contemporary guidelines and consensus do not incorporate these in daily practice. In the future, further studies are required to authenticate and substantiate these findings in order to establish a more standardized approach for clinical implementation.
A Framework to Identify Priority Areas for Restoration: Integrating Human Demand and Ecosystem Services in Dongting Lake Eco-Economic Zone, China
Authors: Zhao Yanping , Luo Jing , Li Tao , Chen Jian , Mi Yi , Wang Kuan
Published: April 2023

The identification of priority restoration areas (PRAs) for ecosystems is a critical step in establishing restoration programs. Because the majority of existing studies focused on improving the ecosystem supply, the PRAs selected are likely to be remote from human demand, and the restoration benefits will not flow to humans. To fill this gap, we constructed an improved framework integrating the ecological restoration projects’ cost and benefits as indicators for choosing PRAs. Then, we identified PRAs for each ecosystem service (ES) with Marxan, and ranked the restoration priority grades according to the superimposed value of PRAs for each ES. Finally, we adjusted the restoration priority grades based on human demand and the concentration of those areas, and chose PRAs with a high ES supply and demand. This framework was applied to the Dongting Lake Eco-Economic Zone, one of China’s most significant ecological restoration project sites. The results indicated that the areas with “high”-, “sub-high”-, and “low”-grade PRAs, based only on the increase in the ES supply, were equal to 82, 410, and 1696 km2, respectively. After considering human demand, the PRAs moved continuously towards places with a high human demand; high-priority areas grew to reach 144 km2, while low-priority areas decreased to 1498 km2. The upgrade of the proposed framework for the identification of PRAs can contribute to increasing human well-being, while also serving as a support tool for environmental restoration management.
Assessing the Negative Effects of Suburbanization: The Urban Sprawl Restrictiveness Index in Romania’s Metropolitan Areas
Authors: Cocheci Radu-Matei , Petrisor Alexandru-Ionut
Published: April 2023

Urban sprawl is widely considered to be a major issue for the functioning of urban areas, threatening long-term sustainability and affecting the quality of living. The aim of this research is to develop a methodology for assessing the negative effects of uncontrolled suburbanization in metropolitan areas through a multicriterial approach. Based on the existing body of knowledge, we have defined a set of indicators for assessing the impact of suburbanization, covering themes such as land use, water, biodiversity and economy or social issues. A questionnaire was applied to experts in the field in order to find out the final set of indicators and their perceived importance. The product of our research is an urban sprawl restrictiveness index at the local level, tested on five of the most dynamic metropolitan areas in Romania. The results highlight the concentration of negative effects of urban sprawl in the areas most accessible from the city core, where additional in-depth analyses were performed for validation. This study thus proposes a novel method for assessing the negative impacts of urban sprawl. The index could be used in other comparative studies at the national or international level while also aiding policymakers in better managing metropolitan areas.
Protecting Poor Rural Households from Health Shocks: Poverty Alleviation Practices in Chongqing, China
Authors: Zhang Qianqian , Li Tao , Tan Xiongwei , Yan Jianzhong
Published: April 2023

In certain low- and middle-income countries, information asymmetry, human capital damage and long-term economic decline are longstanding problems in health-related poverty alleviation. Notably, China’s Targeted Poverty Alleviation program sheds new light on resolving these problems. Based on existing paradigms in the poverty research area, the purpose of this paper is to summarize and explore the roles of Chinese support policies in poor rural households coping with health shocks. Using a questionnaire survey of 4635 poor rural households in a municipality in Southwest China conducted from December 2018 to January 2019, this study examines the relationships between health shocks, human capital, support policies, and per capita household income. The results show that (1) apart from safety nets and cargo nets, monitoring nets are formed in China’s poverty alleviation practice, which could resolve the problem of information asymmetry. (2) Health shocks do not cause poor rural households to fall back into poverty. The reason for this is that safety net and cargo net policies are provided to relevant poor rural households by considering household human capital endowments and the information received from cargo nets. Through this method, patients can obtain effective support and caregivers can obtain off-farm employment opportunities. Thus, the ability of poor rural household human capital to resist health shocks is enhanced. (3) With the support of these policies, the negative effects of dependent family members and agricultural laborers on per capita household income are reversed. Thus, the long-term increase in poor rural household income is also ensured. These findings hold great value for other developing countries coping with health shocks and formulating anti-poverty policies.
Mixed Land Use as an Intrinsic Feature of Sprawl: A Short-Term Analysis of Settlement Growth and Population Distribution Using European Urban Atlas
Authors: D’Agata Alessia , Quaranta Giovanni , Salvia Rosanna , Carlucci Margherita , Salvati Luca
Published: April 2023

This study investigates the land-use/population mix over time as the base to derive an indicator of urban sprawl. Land-use individual patches (provided by Urban Atlas, hereafter UA, with a detailed spatial geometry at 1:10,000 scale) were associated with the total (resident) population based on official statistics (census enumeration districts and other public data sources), providing a comprehensive mapping of the spatial distribution of population density by land-use class in a representative case study for the Mediterranean region (metropolitan Athens, Greece). Data analysis adopted a mix of statistical techniques, such as descriptive statistics, non-parametric curve interpolation (smoothing splines), and exploratory multivariate statistics, namely hierarchical clustering, non-metric multi-dimensional scaling and confirmative factor analysis. The results of this study indicate a non-linear gradient of density decline from downtown (dominated by compact settlements) to peripheral locations (dominated by natural land). Population density in agricultural land was locally high and increasing over time; this result suggests how mixed land use may be the base of intense sprawl in large metropolitan regions. The methodology implemented in this study can be generalized over the whole sample of European cities included in Urban Atlas, providing a semi-automatic assessment of exurban development and population re-distribution over larger metropolitan regions.
Pas de Problème: The Distribution and Nature of Double Negation in French and Other Romance Negative Concord Languages
Authors: Zeijlstra Hedde
Published: April 2023

Most Romance negative concord (NC) languages in particular configurations give rise to double negation (DN) readings. In this article, I discuss an intricate DN pattern in French. After discussing some previous accounts, I provide an analysis of French pas (and in its slipstream also of the French expletive negative element ne) that takes pas to be a purely semantically but not formally (i.e., syntactically) negative element. I then argue that the reason why French pas is so different from other negative markers lies in its diachrony and show that other attested asymmetries between the formal properties of negative markers and neg-words in Romance must receive a diachronic explanation as well.
Gut Microbiota-Derived Short-Chain Fatty Acids: Novel Regulators of Intestinal Serotonin Transporter
Authors: Buey Berta , Forcén Ana , Grasa Laura , Layunta Elena , Mesonero Jose Emilio , Latorre Eva
Published: April 2023

Serotonin (5-HT) is a key neurotransmitter synthesized both in the gut and the central nervous system. It exerts its signaling through specific receptors (5-HTR), which regulate numerous behaviors and functions such as mood, cognitive function, platelet aggregation, gastrointestinal motility, and inflammation. Serotonin activity is determined mainly by the extracellular availability of 5-HT, which is controlled by the serotonin transporter (SERT). Recent studies indicate that, by activation of innate immunity receptors, gut microbiota can modulate serotonergic signaling by SERT modulation. As part of its function, gut microbiota metabolize nutrients from diet to produce different by-products, including short-chain fatty acids (SCFAs): propionate, acetate, and butyrate. However, it is not known whether these SCFAs regulate the serotonergic system. The objective of this study was to analyze the effect of SCFAs on the gastrointestinal serotonergic system using the Caco-2/TC7 cell line that expresses SERT and several receptors constitutively. Cells were treated with different SCFAs concentrations, and SERT function and expression were evaluated. In addition, the expression of 5-HT receptors 1A, 2A, 2B, 3A, 4, and 7 was also studied. Our results show that the microbiota-derived SCFAs regulate intestinal serotonergic system, both individually and in combination, modulating the function and expression of SERT and the 5-HT1A, 5-HT2B, and 5-HT7 receptors expression. Our data highlight the role of gut microbiota in the modulation of intestinal homeostasis and suggest microbiome modulation as a potential therapeutic treatment for intestinal pathologies and neuropsychiatric disorders involving serotonin.
Transcriptome Analysis Reveals Genes Associated with Flooding Tolerance in Mulberry Plants
Authors: Hu Jingtao , Duan Yanyan , Yang Junnian , Gan Liping , Chen Wenjing , Yang Jin , Xiao Guosheng , Guan Lingliang , Chen Jingsheng
Published: April 2023

Mulberry (Morus alba), a widely distributed economic plant, can withstand long-term flooding stress. However, the regulatory gene network underlying this tolerance is unknown. In the present study, mulberry plants were subjected to submergence stress. Subsequently, mulberry leaves were collected to perform quantitative reverse-transcription PCR (qRT-PCR) and transcriptome analysis. Genes encoding ascorbate peroxidase and glutathione S-transferase were significantly upregulated after submergence stress, indicating that they could protect the mulberry plant from flood damage by mediating ROS homeostasis. Genes that regulate starch and sucrose metabolism; genes encoding pyruvate kinase, alcohol dehydrogenase, and pyruvate decarboxylase (enzymes involved in glycolysis and ethanol fermentation); and genes encoding malate dehydrogenase and ATPase (enzymes involved in the TCA cycle) were also obviously upregulated. Hence, these genes likely played a key role in mitigating energy shortage during flooding stress. In addition, genes associated with ethylene, cytokinin, abscisic acid, and MAPK signaling; genes involved in phenylpropanoid biosynthesis; and transcription factor genes also showed upregulation under flooding stress in mulberry plants. These results provide further insights into the adaptation mechanisms and genetics of submergence tolerance in mulberry plants and could aid in the molecular breeding of these plants.
The Protecting Activity of RIPACUT®: A New Therapeutic Approach Preserving Epithelial Health Based on the Combination of Iceland Lichen Extract, Silver Salt, and Sodium Hyaluronate
Authors: Belvedere Raffaella , Novizio Nunzia , Eletto Daniela , Porta Amalia , Di Maio Umberto , Petrella Antonello
Published: April 2023

Epithelial integrity and function must be maintained in a dynamic healthy equilibrium, keeping unaltered the oxidative and inflammatory conditions and the microbiome of the cutaneous layers. Beside the skin, other mucous membranes can be injured, such as the nasal and anal ones, because of the contact with the external environment. Here, we detected the effects of RIPACUT®, a combination of Iceland lichen extract, silver salt and sodium hyaluronate that individually act in diverse biological ways. The findings we obtained on keratinocytes, nasal and intestinal epithelial cells reveal that this combination showed a marked antioxidant activity, further assessed by the DPPH assay. Additionally, by analyzing the release of the IL-1β, TNF-α and IL-6 cytokines, we proved the anti-inflammatory effect of RIPACUT®. In both cases, the main preserving action was due to Iceland lichen. We also observed a notable antimicrobial activity mediated by the silver compound. These data suggest that RIPACUT® could signify the basis for an attractive pharmacological approach to maintaining healthy epithelial conditions. Interestingly, this may be extended to the nasal and anal areas where it protects against oxidative, inflammatory and infectious insults. Thus, these outcomes encourage the creation of sprays or creams for which sodium hyaluronate can guarantee a surface film-forming effect.
COVID-19 and Health Outcomes in People with Multiple Sclerosis: A Population-Based Study in Italy
Authors: Gnavi Roberto , Eboli Ilenia , Alboini Paolo Emilio , D’Alfonso Sandra , Picariello Roberta , Costa Giuseppe , Leone Maurizio
Published: April 2023

People with multiple sclerosis (PWMS) are at high risk of being affected by the disruption of health services that occurred during the COVID-19 pandemic months. The aim of this study was to evaluate the effect of the pandemic on the health outcomes of PWMS. PWMS and MS-free residing in Piedmont (north-west of Italy) were identified from electronic health records and linked with the regional COVID-19 database, the hospital-discharge database, and the population registry. Both cohorts (9333 PWMS and 4,145,856 MS-free persons) were followed-up for access to swab testing, hospitalisation, access to the Intensive Care Unit (ICU), and death from 22 February 2020 to 30 April 2021. The relationship between the outcomes and MS was evaluated using a logistic model, which was adjusted for potential confounders. The rate of swab testing was higher in PWMS, but the positivity to infection was similar to that of MS-free subjects. PWMS had a higher risk of hospitalisation (OR = 1.74; 95% IC, 1.41–2.14), admission to ICU (OR = 1.79; 95% IC, 1.17–2.72), and a slight, albeit not statistically significant, increase in mortality (OR = 1.28; 95% IC, 0.79–2.06). Compared to the general population PWMS with COVID-19 had an increased risk of hospitalization and admission to the ICU; the mortality rate did not differ.
Application of Lactobacillus reuteri B1/1 (Limosilactobacillus reuteri) Improves Immunological Profile of the Non-Carcinogenic Porcine-Derived Enterocytes
Authors: Karaffová Viera , Teleky Jana , Pintarič Maša , Langerholc Tomaž , Mudroňová Dagmar , Hudec Erik , Ševčíková Zuzana
Published: April 2023

In our previous studies, Lactobacillus reuteri B1/1, which was renamed Limosilactobacillus reuteri (L. reuteri), was able to modulate the production of pro-inflammatory cytokines and other components of the innate immune response in vitro and in vivo. In this study, we evaluated the effect of Lactobacillus reuteri B1/1 in two concentrations (1 × 107 and 1 × 109 CFU) on the metabolic activity, adherence ability and relative gene expression of pro-inflammatory interleukins (IL-1β, IL-6, IL-8, IL-18), lumican and olfactomedin 4 produced by non-carcinogenic porcine-derived enterocytes (CLAB). CLAB cells were cultured in a 12-well cell culture plate at a concentration of 4 × 105 cells/well in DMEM medium in a controlled humidified atmosphere for 48 h. A 1 mL volume of each probiotic bacterial suspension was added to the CLAB cells. Plates were incubated for 2 h and 4 h. Our results revealed that L. reuteri B1/1 was able to adhere to CLAB cells in sufficient numbers in both concentrations. In particular, the concentration of 109 L. reuteri B1/1 allowed to modulate the gene expression of pro-inflammatory cytokines, as well as to increase the metabolic activity of the cells. In addition, administration of L. reuteri B1/1 in both concentrations significantly stimulated gene expression for both proteins in the CLAB cell line after 4 h of incubation.
Coated Piston Ring Pack and Cylinder Liner Elastodynamics in Correlation to Piston Subsystem Elastohydrodynamic: Through FEA Modelling
Authors: Mishra Prakash Chandra , Roychoudhury Arka , Banerjee Ayan , Saha Nutan , Das Sudhansu Ranjan , Das Anshuman
Published: April 2023

A finite element model is developed to assess the effects of the TiSiCN thin film coating of the piston ring on the structural strength of the piston subsystem. The complex, cyclically variable forces are considered in load and boundary conditions. The model included combustion dynamics, contact kinetics, piston subsystem primary and secondary motions, and lubricated contact conditions to evaluate the applied forces. A comparative analysis is performed for coated and uncoated cases. Four different crown geometries are tried for selecting the best case of crown design for coated piston subsystem components. The analysis predicts better strength in coated cases compared to uncoated ones. The type-A crown design develops less stress, while the compression ring suffers the most due to elastic deformation and is more prone to fatigue failure.