bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there room in epilepsy for the claustrum?
Authors: Watson Glenn D. R. , Meletti Stefano , Mahavadi Anil K. , Besson Pierre , Bandt S. Kathleen , Smith Jared B.
Published: April 2024

The function of the claustrum and its role in neurological disorders remains a subject of interest in the field of neurology. Given the claustrum’s susceptibility to seizure-induced damage, there is speculation that it could serve as a node in a dysfunctional epileptic network. This perspective article aims to address a pivotal question: Does the claustrum play a role in epilepsy? Building upon existing literature, we propose the following hypotheses for the involvement of the claustrum in epilepsy: (1) Bilateral T2/FLAIR magnetic resonance imaging (MRI) hyperintensity of the claustrum after status epilepticus represents a radiological phenomenon that signifies inflammation-related epileptogenesis; (2) The ventral claustrum is synonymous with a brain area known as ‘area tempestas,’ an established epileptogenic center; (3) The ventral subsector of the claustrum facilitates seizure generalization/propagation through its connections with limbic and motor-related brain structures; (4) Disruption of claustrum connections during seizures might contribute to the loss of consciousness observed in impaired awareness seizures; (5) Targeting the claustrum therapeutically could be advantageous in seizures that arise from limbic foci. Together, evidence from both clinical case reports and animal studies identify a significant role for the ventral claustrum in the generation, propagation, and intractable nature of seizures in a subset of epilepsy syndromes.
Application of Convolutional Neural Networks in Weed Detection and Identification: A Systematic Review
Authors: García-Navarrete Oscar Leonardo , Correa-Guimaraes Adriana , Navas-Gracia Luis Manuel
Published: April 2024

Weeds are unwanted and invasive plants that proliferate and compete for resources such as space, water, nutrients, and sunlight, affecting the quality and productivity of the desired crops. Weed detection is crucial for the application of precision agriculture methods and for this purpose machine learning techniques can be used, specifically convolutional neural networks (CNN). This study focuses on the search for CNN architectures used to detect and identify weeds in different crops; 61 articles applying CNN architectures were analyzed during the last five years (2019–2023). The results show the used of different devices to acquire the images for training, such as digital cameras, smartphones, and drone cameras. Additionally, the YOLO family and algorithms are the most widely adopted architectures, followed by VGG, ResNet, Faster R-CNN, AlexNet, and MobileNet, respectively. This study provides an update on CNNs that will serve as a starting point for researchers wishing to implement these weed detection and identification techniques.
The Effects of Rock Zones and Tea Tree Varieties on the Growth and Quality of Wuyi Rock Tea Based on the OPLS-DA Model and Machine Learning
Authors: Ye Jianghua , Zhang Qi , Jia Miao , Wang Yuhua , Zhang Ying , Jia Xiaoli , Zheng Xinyu , Wang Haibin
Published: April 2024

Rock zones have an important influence on the yield and quality of Wuyi rock tea. In this study, OPLS-DA combined with machine learning was used to analyze the effects of different rock zones and tea tree varieties on the physicochemical properties of rhizosphere soil, the growth of the tea tree and the quality of the tea leaves using tea trees in different rock zones. The results showed that rock zones had significant effects on rhizosphere soil physicochemical indexes, soil enzyme activities, tea tree growth and tea quality indexes, while there was little difference between different tea tree varieties. The interaction analysis showed that the physicochemical indexes of rhizosphere soil in different rock zones significantly affected tea quality, while also affecting growth indexes. The main indexes affecting tea yield and caffeine content were soil pH, available nitrogen, total phosphorus, total nitrogen and available phosphorus, while the main indexes affecting tea quality were available potassium, organic matter, total potassium, protease, polyphenol oxidase and urease. Analyses of PCA, OPLS-DA models and KNN and ANN machine learning showed that different rock zones could be effectively distinguished from each other with 100% accuracy, while different tea varieties had little difference and could not be distinguished. TOPSIS analysis found that the physicochemical indexes most affected by rock zone were available nitrogen, available potassium and sucrose, and the quality indexes most affected by rock zone were tea polyphenols and theanine. The growth index most affected by rock zone was tea yield. It was evident that the key difference between tea trees in different rock zones was yield and quality, with high yields in continent zones, and good quality in semi-rock zones and rock zones. This study provides a crucial foundation for tea-plantation management, the artificial regulation of tea yield and the quality of different rock zones of Wuyi rock tea.
Effects of the Plastic Mulching System and Fertilizer Application on the Yield of Tartary Buckwheat (Fagopyrum tataricum) and Water Consumption Characteristics in a Semi-Arid Area
Authors: Fang Yanjie , Zhang Xucheng , Li Lingling , Effah Zechariah , Muhammad Nizamani Mir
Published: April 2024

Although plastic film mulching is commonly utilized to enhance crop water use efficiency (WUE) in semi-arid areas, the combined effect of plastic film mulching and fertilizer application on Tartary buckwheat yield is still unknown. To address this gap, a four-year field experiment was conducted from 2018 to 2021 to investigate the effect of plastic film mulching and fertilizers on the soil water storage, plant growth, yield, and WUE of Tartary buckwheat in semi-arid environments. The treatments comprised traditional planting without fertilizer (TNF), traditional planting with fertilizer application (N–P2O5–K2O: 40–30–20 kg ha−1) (TF), plastic film mulching with fertilizer application (N–P2O5–K2O: 40–30–20 kg ha−1) (MF), and plastic film mulching without fertilizer (MNF). The results indicated that MF treatment significantly increased leaf area index and SPAD values compared to the other treatments. The yield of Tartary buckwheat under the film mulching increased by 23.3% in comparison to no-mulching treatments, and under fertilizer application it increased by 18.2% compared to no fertilizer. WUE under film mulching exhibited an increase of 3.1% in 2018, 34.9% in 2019, 45.5% in 2020, and 34.6% in 2021, respectively, compared to no mulching. The impact of film mulching on WUE was more significant in years with lower precipitation compared to those with normal or higher precipitation levels. Overall, MF significantly enhanced both the yield and WUE of Tartary buckwheat. This approach proved to be an effective strategy for bolstering drought-resistant yield and optimizing resource efficiency in Tartary buckwheat cultivation in semi-arid regions. Moreover, the positive effects of plastic mulching and fertilizer application on grain yield and water use efficiency were more pronounced in drier years.
Case Studies on Sustainability-Oriented Innovations and Smart Farming Technologies in the Wine Industry: A Comparative Analysis of Pilots in Cyprus and Italy
Authors: Kasimati Aikaterini , Papadopoulos George , Manstretta Valentina , Giannakopoulou Marianthi , Adamides George , Neocleous Damianos , Vassiliou Vassilis , Savvides Savvas , Stylianou Andreas
Published: April 2024

Addressing the urgent sustainability challenges in the wine industry, this study explores the efficacy of sustainability-oriented innovations (SOIs) and smart farming technologies (SFTs) across wine value chains in Cyprus and Italy. Utilising a mixed-methods approach that includes quantitative analysis through Key Performance Indicators (KPIs) and qualitative assessments to understand stakeholders’ perspectives, this research delves into the environmental, economic, and social impacts of these technologies. In Cyprus, the integration of digital labelling and smart farming solutions led to a substantial reduction in pesticide usage by up to 75% and enhanced the perceived quality of wine by an average of 8%. A pilot study in Italy witnessed a 33.4% decrease in greenhouse gas emissions, with the additional benefit of a 5.3% improvement in intrinsic product quality. The pilot introduced a carbon credit system, potentially generating an average annual revenue of EUR 4140 per farm. These findings highlight the transformative potential of SOIs and SFTs in promoting sustainable practices within the wine industry, demonstrating significant advancements in reducing environmental impact, improving product quality, and enhancing economic viability. This study underscores the critical role of innovative technologies in achieving sustainability goals and provides a compelling case for their wider adoption within the agricultural sector.
Polyphenol Profile, Antioxidant Activity and Yield of Cynara cardunculus altilis in Response to Nitrogen Fertilisation
Authors: Sałata Andrzej , Nurzyńska-Wierdak Renata , Lombardo Sara , Pandino Gaetano , Mauromicale Giovanni , Ibáñez-Asensio Sara , Moreno-Ramón Héctor , Kalisz Andrzej
Published: April 2024

Cardoon leaves are of great pharmaceutical importance due to their high content of polyphenol compounds. Polyphenolic compounds have attracted much interest due to their health-promoting effects. The content of these compounds in C. cardunculus depends on several factors, such as genotype, crop management, plant tissues, harvest time, and storage time. In this study, the effects of nitrogen (N) fertilisation (rates and forms) on the biomass yield and polyphenol profile of the leaves were determined. Increasing the amount of N up to 180 kg-ha−1 in fertilisation did not significantly increase the air-dried biomass yield of the leaves. On the contrary, it led to lower concentrations of total phenolic compounds (TP), total flavonoids (TF), caffeic acid, cynarin, and luteolin. Improvements in performance were achieved when 120 kg-ha−1 N rate was applied and increases in TP, TF content, and radical scavenging activity were observed. The applied N forms (NO3, NH4 or urea) had different effects on the concentrations of individual compounds and leaf air-dried biomass. Higher concentrations of cynarin, luteolin, and luteolin-7-O-glucoside were found when the N forms NH4 and urea were applied; higher caffeic acid content was found when urea was applied. The application of NO3 and urea in fertilisation reduced the level of luteolin-7-O-rutinoside, while the application of NO3 and NH4 reduced the amount of caffeic acid. The obtained results provide a better understanding of the effects of N rates and forms on cardoon leaves over two growing seasons.
Effects of Boron and Zinc Micro-Fertilizer on Growth and Quality of Jujube Trees (Ziziphus jujuba) in the Desert Area
Authors: Tao Wanghai , Zeng Senlin , Yan Kuihao , Alwahibi Mona S. , Shao Fanfan
Published: April 2024

Jujubes (Ziziphus jujuba) are a crucial industry in the arid region of Xinjiang, facing challenges such as water scarcity and low water use efficiency. This study focuses on jujube orchards located at the edge of the Taklimakan Desert to investigate whether applying trace elements can effectively enhance jujube growth, development, and fruit quality. By foliar spraying boron and zinc micro-fertilizers onto jujube leaves, we analyzed the effects of different doses on growth parameters, photosynthetic activity, crop yield, water use efficiency, and fruit quality. The results revealed that the length of the fruit branch, leaf area index, and fruit longitudinal/transverse diameter increased by 19.35%, 25.72%, and 32.9%/2.28%, respectively; net photosynthetic rate, transpiration rate, and stomatal conductance increased by 105.51%, 91.43%, and 75.3%, respectively, while intercellular CO2 concentration decreased by 13.09%; yield and water use efficiency improved by 16.95% and 12.68%, respectively; soluble sugar content, titratable acid content, and flavonoid content increased by 13.56%, 51.63%, and 86.12%, respectively. Based on these findings, the optimal application rate for boron micro-fertilizer was determined to be 3.51~3.59 kg/hm2, and for zinc micro-fertilizer, it was 3.16~3.32 kg/hm2. This study provides practical methods along with theoretical support for applying micro-fertilizers in arid regions.
Mycorrhizal Fungi in Sustainable Agriculture and Land Restoration
Authors: Karunarathna Samantha C.
Published: April 2024

The term ‘Mycorrhiza’ refers to the symbiotic relationship between fungi and plant roots, particularly in terrestrial environments [...]
Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients
Authors: Xi Lin , Li Shanshan , Chen Mengting , Huang Xiaolan , Li Nanyang , Chen Nanye , Wu Hailan , Bian Qiyu , Bian Xingchen , Li Xin , Yang Minjie , Liang Xiaoyu , Wu Jufang , Guo Beining , Fan Yaxin , Zhang Jing
Published: April 2024

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18–64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.
Candida auris Outbreak in a Multidisciplinary Hospital in Romania during the Post-Pandemic Era: Potential Solutions and Challenges in Surveillance and Epidemiological Control
Authors: Melinte Violeta , Tudor Alexandra Daniela , Bujoi Adrian Georgian , Radu Maria-Adelina , Văcăriou Maria Cristina , Cismaru Ioana Miriana , Holban Tiberiu Sebastian , Mîrzan Carmen Luminița , Popescu Ruxandra , Ciupan Robert Cătălin , Baciu Alin , Moraru Oriana Elena , Popa-Cherecheanu Matei , Gheorghiță Valeriu
Published: April 2024

Candida auris is a newly emerging yeast, which is raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals, and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analyzed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could only be traced in 10 patients, according to the epidemiologic investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first positive case detected.
Development and Characterization of Modified Gelatin-Based Cling Films with Antimicrobial and Antioxidant Activities and Their Application in the Preservation of Cherry Tomatoes
Authors: Qiao Jianfu , Wang Linjing , Wang Luxin , Li Ziyan , Huai Yue , Zhang Shaoying , Yu Youwei
Published: April 2024

The utilization of functional cling films presents a promising approach to alleviate post-harvest spoilage caused by microbial activity, oxidative metabolism, and moisture loss in agricultural products. To overcome the environmental problems of conventional packaging materials, in this study, we developed functional fruit and vegetable cling films based on glycidyltrimethylammonium chloride and rosemarinic acid cross-linked gelatin (RQ-GEL). The results indicate that the prepared RQ-GEL film possesses excellent UV light barrier properties and mechanical performance. RQ-GEL inhibited S. aureus and E. coli by 93.79% and 92.04%, respectively. DPPH and ABTS free radical scavenging activities were as high as 87.69% and 84.6%. In the cherry tomato preservation experiment, when compared to uncovered samples, the RQ-GEL group had a 29.77% reduction in weight loss and a significant 26.92% reduction in hardness. Meanwhile, the RQ-GEL group delays the decline of fruit total soluble solids and titratable acidity content, and prolongs the preservation period of cherry tomatoes. Hence, RQ-GEL cling film is poised to emerge as a promising packaging material for the post-harvest preservation of agricultural products.
Nitrosative Stress in Astronaut Skeletal Muscle in Spaceflight
Authors: Blottner Dieter , Moriggi Manuela , Trautmann Gabor , Furlan Sandra , Block Katharina , Gutsmann Martina , Torretta Enrica , Barbacini Pietro , Capitanio Daniele , Rittweger Joern , Limper Ulrich , Volpe Pompeo , Gelfi Cecilia , Salanova Michele
Published: April 2024

Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR changes in deep calf soleus muscle. Nitro-DIGE analyses identified functional proteins (structural, metabolic, mitochondrial) that were over-nitrosylated post- vs. preflight. In a short-duration mission (SDM) astronaut (9 ISS days), s-nitrosylation of a nodal protein of the glycolytic flux, specific proteins in tricarboxylic acid (TCA) cycle, respiratory chain, and over-nitrosylation of creatine kinase M-types as signs of impaired ATP production and muscle contraction proteins were seen. S-nitrosylation of serotransferrin (TF) or carbonic anhydrase 3 (CA3b and 3c) represented signs of acute response microgravity muscle maladaptation. LDM nitrosoprofiles reflected recovery of mitochondrial activity, contraction proteins, and iron transporter TF as signs of muscle adaptation to microgravity. Nitrosated antioxidant proteins, alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR), and selenoprotein thioredoxin reductase 1 (TXNRD1) levels indicated signs of altered redox homeostasis and reduced protection from nitrosative stress in spaceflight. This work presents a novel spaceflight-generated dataset on s-nitrosylated muscle protein signatures from astronauts that helps both to better understand the structural and molecular networks associated to muscular nitrosative stress and to design countermeasures to dysfunction and impaired performance control in human spaceflight missions.
Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease
Authors: Staurenghi Erica , Testa Gabriella , Leoni Valerio , Cecci Rebecca , Floro Lucrezia , Giannelli Serena , Barone Eugenio , Perluigi Marzia , Leonarduzzi Gabriella , Sottero Barbara , Gamba Paola
Published: April 2024

Down syndrome (DS) is a complex chromosomal disorder considered as a genetically determined form of Alzheimer’s disease (AD). Maintenance of brain cholesterol homeostasis is essential for brain functioning and development, and its dysregulation is associated with AD neuroinflammation and oxidative damage. Brain cholesterol imbalances also likely occur in DS, concurring with the precocious AD-like neurodegeneration. In this pilot study, we analyzed, in the brain of the Ts2Cje (Ts2) mouse model of DS, the expression of genes encoding key enzymes involved in cholesterol metabolism and of the levels of cholesterol and its main precursors and products of its metabolism (i.e., oxysterols). The results showed, in Ts2 mice compared to euploid mice, the downregulation of the transcription of the genes encoding the enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and 24-dehydrocholesterol reductase, the latter originally recognized as an indicator of AD, and the consequent reduction in total cholesterol levels. Moreover, the expression of genes encoding enzymes responsible for brain cholesterol oxidation and the amounts of the resulting oxysterols were modified in Ts2 mouse brains, and the levels of cholesterol autoxidation products were increased, suggesting an exacerbation of cerebral oxidative stress. We also observed an enhanced inflammatory response in Ts2 mice, underlined by the upregulation of the transcription of the genes encoding for α-interferon and interleukin-6, two cytokines whose synthesis is increased in the brains of AD patients. Overall, these results suggest that DS and AD brains share cholesterol cycle derangements and altered oxysterol levels, which may contribute to the oxidative and inflammatory events involved in both diseases.
Calibration Method of PFC3D Micro-Parameters under Impact Load
Authors: Zhang Zehua , Gao Wenle , Kou Yuming
Published: April 2024

Micro-parameter calibration is essential in constructing an accurate and reliable numerical model of particle discrete element PFC3D 6.0 software. Micro-parameter calibration is mainly accomplished according to the macro-parameters obtained from static or quasi-static laboratory tests such as UCS. However, there is little current research concerning the calibration method under impact load. An SJM micro-parameter calibration method, based on the SHPB rock test and the FLAC3D/PFC3D coupling method, is proposed to solve this problem. Firstly, UCS, SHPB, and other laboratory rock tests were carried out to determine the rock sample’s macroscopic physical and mechanical parameters. Secondly, the FLAC3D/PFC3D numerical coupling model of the SHPB test was established, and the single-factor and double-factor orthogonal numerical simulation was carried out. Then, the main micro-parameters that affect the macroscopic physical and mechanical parameters of the SJM particle discrete element model were proposed. Finally, the quantitative relationship between the model’s macro-parameters and micro-parameters was established through multiple linear regression. A set of PFC3D micro-parameter calibration processes under impact load was established. The relative errors of the macro-parameters obtained from laboratory and numerical tests totaled less than 5%, which further verifies the rationality of the calibration method. This method provides some reference values for PFC3D micro-parameter calibration under impact load.
Overlay-ML: Unioning Memory and Storage Space for On-Device AI on Mobile Devices
Authors: Kwon Cheolhyeon , Kang Donghyun
Published: April 2024

Recently, the technologies of on-device AI have been accelerated with the development of new hardware and software platforms. Therefore, many researchers and engineers focus on how to enable ML technologies on mobile devices with limited hardware resources. In this paper, we revisit on-device ML designed to support ML technologies on mobile devices and describe the three challenges when using on-device ML in detail. Then, we propose a new data management policy, called Overlay-ML, which efficiently solves two challenges that we discovered. Especially, we designed Overlay-ML to work in the application space with two key ideas. The first key idea is to extend the limited memory space using the usable space of the underlying storage device. The second key idea is to provide data transparency, which hides where the data is stored so that running ML models think the data is stored in the same place. For evaluation, we implemented an image detection application based on TensorFlow Lite which is a well-known on-device ML framework, and modified it to enable the features of Overlay-ML. All evaluation was performed on two state-of-the-art smartphones that are high-end embedded devices. Our evaluation results clearly show Overlay-ML can effectively prevent unexpected termination by Android OS and present a good loss value in real-world workload.
Na4Fe3(PO4)2(P2O7)@C/Ti3C2Tx Hybrid Cathode Materials with Enhanced Performances for Sodium-Ion Batteries
Authors: Xiang Ao , Shi Deyou , Chen Peng , Li Zhongjun , Tu Quan , Liu Dahui , Zhang Xiangguang , Lu Jun , Jiang Yan , Yang Ze , Hu Pei
Published: April 2024

Developing cost-effective cathode materials is conducive to accelerating the commercialization of sodium-ion batteries. Na4Fe3(PO4)2P2O7 (NFPP) has attracted extensive attention owning to its high theoretical capacity, stable structure, and low cost of raw materials. However, its inherent low conductivity hinders its further application. Herein, carbon-coated NFPP nanospheres are anchored to crumpled MXene nanosheets by an electrostatic self-assembly; this cross-linked structure induced by CTAB not only significantly expands the contact area between particles and improves the electronic conductivity, but also effectively reduces the aggregation of NFPP nanoparticles. The as-designed Na4Fe3(PO4)2(P2O7)@C/Ti3C2Tx (NFPP@MX) cathode exhibits a high discharge capacity (106.1 mAh g−1 g at 0.2 C), good rate capability (60.4 mAh g−1 at 10 C), and a long-life cyclic stability (85.2% capacity retention after 1000 cycles at 1 C). This study provides an effective strategy for the massive production of high-performance NFPP cathodes and broadens the application of MXene in the modification of other cathode materials.
Post-Stroke Functional Changes: In-Depth Analysis of Clinical Tests and Motor-Cognitive Dual-Tasking Using Wearable Sensors
Authors: Abdollahi Masoud , Rashedi Ehsan , Kuber Pranav Madhav , Jahangiri Sonia , Kazempour Behnam , Dombovy Mary , Azadeh-Fard Nasibeh
Published: April 2024

Clinical tests like Timed Up and Go (TUG) facilitate the assessment of post-stroke mobility, but they lack detailed measures. In this study, 21 stroke survivors and 20 control participants underwent TUG, sit-to-stand (STS), and the 10 Meter Walk Test (10MWT). Tests incorporated single tasks (STs) and motor-cognitive dual-task (DTs) involving reverse counting from 200 in decrements of 10. Eight wearable motion sensors were placed on feet, shanks, thighs, sacrum, and sternum to record kinematic data. These data were analyzed to investigate the effects of stroke and DT conditions on the extracted features across segmented portions of the tests. The findings showed that stroke survivors (SS) took 23% longer for total TUG (p < 0.001), with 31% longer turn time (p = 0.035). TUG time increased by 20% (p < 0.001) from STs to DTs. In DTs, turning time increased by 31% (p = 0.005). Specifically, SS showed 20% lower trunk angular velocity in sit-to-stand (p = 0.003), 21% longer 10-Meter Walk time (p = 0.010), and 18% slower gait speed (p = 0.012). As expected, turning was especially challenging and worsened with divided attention. The outcomes of our study demonstrate the benefits of instrumented clinical tests and DTs in effectively identifying motor deficits post-stroke across sitting, standing, walking, and turning activities, thereby indicating that quantitative motion analysis can optimize rehabilitation procedures.
Sleeping for One Week on a Temperature-Controlled Mattress Cover Improves Sleep and Cardiovascular Recovery
Authors: Moyen Nicole E. , Ediger Tatiana R. , Taylor Kathryn M. , Hancock Erin G. , Holden Lucas D. , Tracy Emma E. , Kay Philip H. , Irick Charles R. , Kotzen Kevin J. , He David D.
Published: April 2024

Body temperature should be tightly regulated for optimal sleep. However, various extrinsic and intrinsic factors can alter body temperature during sleep. In a free-living study, we examined how sleep and cardiovascular health metrics were affected by sleeping for one week with (Pod ON) vs. without (Pod OFF), an active temperature-controlled mattress cover (the Eight Sleep Pod). A total of 54 subjects wore a home sleep test device (HST) for eight nights: four nights each with Pod ON and OFF (>300 total HST nights). Nightly sleeping heart rate (HR) and heart rate variability (HRV) were collected. Compared to Pod OFF, men and women sleeping at cooler temperatures in the first half of the night significantly improved deep (+14 min; +22% mean change; p = 0.003) and REM (+9 min; +25% mean change; p = 0.033) sleep, respectively. Men sleeping at warm temperatures in the second half of the night significantly improved light sleep (+23 min; +19% mean change; p = 0.023). Overall, sleeping HR (−2% mean change) and HRV (+7% mean change) significantly improved with Pod ON (p < 0.01). To our knowledge, this is the first study to show a continuously temperature-regulated bed surface can (1) significantly modify time spent in specific sleep stages in certain parts of the night, and (2) enhance cardiovascular recovery during sleep.
Analysis of Self-Assembled Low- and High-Molecular-Weight Poly-L-Lysine–Ce6 Conjugate-Based Nanoparticles
Authors: Seo Minho , Lee Kyeong-Ju , Seo Bison , Lee Jun-Hyuck , Lee Jae-Hyeon , Shin Dong-Wook , Park Jooho
Published: April 2024

In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.
Antiviral Drug Candidate Repositioning for Streptococcus suis Infection in Non-Tumorigenic Cell Models
Authors: van Niekerk Ashley Anzet , Maluck Sara , Mag Patrik , Kővágó Csaba , Kerek Ádám , Jerzsele Ákos , Steinmetzer Torsten , Pászti-Gere Erzsébet
Published: April 2024

The increasing prevalence of antimicrobial resistance against zoonotic bacteria, including Streptococcus (S.) suis, highlights the need for new therapeutical strategies, including the repositioning of drugs. In this study, susceptibilities of bacterial isolates were tested toward ten different 3-amidinophenyalanine (Phe(3-Am)) derivatives via determination of minimum inhibitory concentration (MIC) values. Some of these protease inhibitors, like compounds MI-432, MI-471, and MI-476, showed excellent antibacterial effects against S. suis. Their drug interaction potential was investigated using human liver microsomal cytochrome P450 (CYP450) measurements. In our work, non-tumorigenic IPEC-J2 cells and primary porcine hepatocytes were infected with S. suis, and the putative beneficial impact of these inhibitors was investigated on cell viability (Neutral red assay), on interleukin (IL)-6 levels (ELISA technique), and on redox balance (Amplex red method). The antibacterial inhibitors prevented S. suis-induced cell death (except MI-432) and decreased proinflammatory IL-6 levels. It was also found that MI-432 and MI-476 had antioxidant effects in an intestinal cell model upon S. suis infection. Concentration-dependent suppression of CYP3A4 function was found via application of all three inhibitors. In conclusion, our study suggests that the potential antiviral Phe(3-Am) derivatives with 2′,4′ dichloro-biphenyl moieties can be considered as effective drug candidates against S. suis infection due to their antibacterial effects.
Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction—In Vivo Pig Model Study
Authors: Bil-Lula Iwona , Kuliczkowski Wiktor , Krzywonos-Zawadzka Anna , Frydrychowski Piotr , Stygar Dominika , Hałucha Kornela , Noszczyk-Nowak Agnieszka
Published: April 2024

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 μM), ML-7 (0.5 μM), and L-NAME (2 μM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.
Exome Sequencing to Identify Novel Variants Associated with Secondary Amenorrhea and Premature Ovarian Insufficiency (POI) in Saudi Women
Authors: Almatrafi Ahmed M. , Hibshi Ali M. , Basit Sulman
Published: April 2024

Background and objectives: Post-pubertal disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion is a heterogeneous condition. Patients with this disease have low levels of gonadal hormones and high levels of gonadotropins. It is one of the causes of female infertility and a strong genetic component is attributed as an underlying cause of this condition. Although variants in several genes have been associated with the condition, the cause of the disease remains undetermined in the vast majority of cases. Methodology and Materials: Ten Saudi married women experiencing secondary amenorrhea were referred to a center for genetics and inherited diseases for molecular investigation. A family-based study design was used. Intensive clinical examinations, including pelvic ultra-sonography (U/S) and biochemical evaluations, were carried out. Karyotypes were normal in all cases and polycystic ovarian syndrome (PCOS) was excluded by using Rotterdam consensus criteria. Patients’ DNA samples were whole-exome sequenced (WES). Bidirectional Sanger sequencing was then utilized to validate the identified candidate variants. The pathogenicity of detected variants was predicted using several types of bioinformatics software. Results: Most of the patients have a normal uterus with poor ovarian reserves. Exome sequence data analysis identified candidate variants in genes associated with POI in 60% of cases. Novel variants were identified in HS6ST1, MEIOB, GDF9, and BNC1 in POI-associated genes. Moreover, a homozygous variant was also identified in the MMRN1 gene. Interestingly, mutations in MMRN1 have never been associated with any human disease. The variants identified in this study were not present in 125 healthy Saudi individuals. Conclusions: WES is a powerful tool to identify the underlying variants in genetically heterogeneous diseases like secondary amenorrhea and POI. In this study, we identified six novel variants and expanded the genotype continuum of POI. Unravelling the genetic landscape of POI will help in genetic counselling, management, and early intervention.
Evaluating p-tau217 and p-tau231 as Biomarkers for Early Diagnosis and Differentiation of Alzheimer’s Disease: A Narrative Review
Authors: Jarek Dorian Julian , Mizerka Hubert , Nuszkiewicz Jarosław , Szewczyk-Golec Karolina
Published: April 2024

The escalating prevalence of Alzheimer’s disease (AD) highlights the urgent need to develop reliable biomarkers for early diagnosis and intervention. AD is characterized by the pathological accumulation of amyloid-beta plaques and tau neurofibrillary tangles. Phosphorylated tau (p-tau) proteins, particularly p-tau217 and p-tau231, have been identified as promising biomarker candidates to differentiate the disease progression from preclinical stages. This narrative review is devoted to a critical evaluation of the diagnostic accuracy, sensitivity, and specificity of p-tau217 and p-tau231 levels in the detection of AD, measured in plasma, serum, and cerebrospinal fluid, compared to established biomarkers. Additionally, the efficacy of these markers in distinguishing AD from other neurodegenerative disorders is examined. The significant advances offered by p-tau217 and p-tau231 in AD diagnostics are highlighted, demonstrating their unique utility in early detection and differential diagnosis. This comprehensive analysis not only confirms the excellent diagnostic capabilities of these markers, but also deepens the understanding of the molecular dynamics of AD, contributing to the broader scientific discourse on neurodegenerative diseases. This review is aimed to provide key information for researchers and clinicians across disciplines, filling interdisciplinary gaps and highlighting the role of p-tau proteins in revolutionizing AD research and clinical practice.
Dual Anti-Inflammatory and Anticancer Activity of Novel 1,5-Diaryl Pyrazole Derivatives: Molecular Modeling, Synthesis, In Vitro Activity, and Dynamics Study
Authors: Deivasigamani Priya , Rubavathy S. M. Esther , Jayasankar Narayanan , Saravanan Venkatesan , Thilagavathi Ramasamy , Prakash Muthuramalingam , Selvam Chelliah , Rajagopal Rajakrishnan , Alfarhan Ahmed , Kathiravan Muthu Kumaradoss , Arokiyaraj Selvaraj , Arockiaraj Jesu
Published: April 2024

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The designed molecules were then further subjected to ADMET and molecular docking studies. Out of 34 designed compounds, the top-10 molecules from the computation studies were synthesized, characterized, and evaluated for COX-2 inhibition and anti-cancer activity. Initially, the target compounds were screened for the protein denaturation assay. The results of the top-five molecules T2, T3, T5, T6, and T9 were further subjected to in vitro COX-2 enzymatic assay and anti-cancer activity. As far as COX-2 inhibitory activity is considered, two compounds, T3 and T5, exhibited the half maximum inhibitory concentration (IC50) at 0.781 µM and 0.781 µM respectively. Further, the two compounds T3 and T5, when evaluated for COX-1 inhibition, exhibited excellent inhibitory activity with T3 IC50 of 4.655μM and T5 with IC50 of 5.596 μM. The compound T5 showed more significant human COX-2 inhibition, with a selectivity index of 7.16, when compared with T3, which had a selectivity index of 5.96. Further, in vitro anti-cancer activity was screened against two cancer cell lines in which compounds T2 and T3 were active against A549 cell lines and T6 was active against the HepG2 cell line. Stronger binding energy was found by comparing MM-PBSA simulations with molecular docking, which suggests that compounds T3 and T5 have a better possibility of being effective compounds, in which T5 showed higher binding affinity. The results suggest that these compounds have the potential to develop effective COX-2 inhibitors as anti-cancer agents.
Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?
Authors: Latreche Amina , Dissaux Gurvan , Querellou Solène , Mazouz Fatmi Doria , Lucia François , Bordron Anais , Vu Alicia , Touati Ruben , Nguyen Victor , Hamya Mohamed , Dissaux Brieg , Bourbonne Vincent
Published: April 2024

Purpose: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [18F]-FET PET/CT. Materials and Methods: Thirty prospectively included patients with histologically confirmed HGGs underwent a PET/CT and mpMRI including diffusion-weighted imaging (DWI: b0, b1000, ADC), contrast-enhanced T1-weighted imaging (T1-Gado), T2-weighted fluid-attenuated inversion recovery (T2Flair), and perfusion-weighted imaging with computation of relative cerebral blood volume (rCBV) and K2 maps. Nine radiation oncologists delineated the PET/CT and MRI sequences. Spatial similarity (Dice similarity coefficient: DSC) was calculated between the readers for each sequence. Impact of the DSC on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan–Meier curves and the log-rank test. Results: The highest DSC mean values were reached for morphological sequences, ranging from 0.71 +/− 0.18 to 0.84 +/− 0.09 for T2Flair and T1Gado, respectively, while metabolic volumes defined by PET/CT achieved a mean DSC of 0.75 +/− 0.11. rCBV variability (mean DSC0.32 +/− 0.20) significantly impacted PFS (p = 0.02) and OS (p = 0.002). Conclusions: Our data suggest that the T1-Gado and T2Flair sequences were the most reproducible sequences, followed by PET/CT. Reproducibility for functional sequences was low, but rCBV inter-reader similarity significantly impacted PFS and OS.
Identification and Diagnosis of Complete Haptoglobin Gene Deletion, One of the Genes Responsible for Adverse Posttransfusion Reactions
Authors: Soejima Mikiko , Koda Yoshiro
Published: April 2024

Allergic reactions are the most frequent adverse events in blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The cause of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HPdel) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes for HPdel have complete Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HPdel is found in East and Southeast Asian populations, with a frequency of approximately 0.9% to 4%, but not in other populations. Diagnosis of Hp deficiency due to HPdel prior to transfusion is advisable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administering plasma products obtained from an Hp-deficient donor pool. This review outlines the background of the identification of HPdel and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HPdel.
Natural Products as Regulators against Matrix Metalloproteinases for the Treatment of Cancer
Authors: Islam Md. Towhedul , Jang Nak Han , Lee Hyuck Jin
Published: April 2024

Cancers are currently the major cause of mortality in the world. According to previous studies, matrix metalloproteinases (MMPs) have an impact on tumor cell proliferation, which could lead to the onset and progression of cancers. Therefore, regulating the expression and activity of MMPs, especially MMP-2 and MMP-9, could be a promising strategy to reduce the risk of cancers. Various studies have tried to investigate and understand the pathophysiology of cancers to suggest potent treatments. In this review, we summarize how natural products from marine organisms and plants, as regulators of MMP-2 and MMP-9 expression and enzymatic activity, can operate as potent anticancer agents.
Photodynamic Therapy for the Treatment of Bowen’s Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome
Authors: Antonetti Paolo , Pellegrini Cristina , Caponio Chiara , Bruni Manfredo , Dragone Lorenzo , Mastrangelo Mirco , Esposito Maria , Fargnoli Maria Concetta
Published: April 2024

Bowen’s disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen’s disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.