bluuebunny/crossref_metadata_2025 huggingface dataset:
ChannelCOMB Device for Mesostructured Reactors and Networks of Reactors
Authors: Barbosa Isabel S. O. , Costa João M. , Manrique Yaidelin A. , Dias Madalena M. , Faria Joaquim L. , Santos Ricardo J. , Silva Cláudia G. , Brito Margarida S. C. A.
Published: February 2023

ChannelCOMB, a consecutive flow distributor, was constructed by additive manufacturing (AM) for experimental validation. The feasibility of using AM was experimentally analyzed for two techniques: stereolithography (tolerance of 50 µm) and fused deposition modeling (tolerance of 100 µm). For the best ChannelCOMB configuration, SLA printing shows a maximum of ca. 4 % in flow deviation, while FDM has a maximum of ca. 15 %. Thus, the SLA technique promotes better flow uniformity due to the fabrication tolerance and material permeability. The results also show that the experimental flow distribution measured for the best ChannelCOMB configuration printed by SLA can be well predicted by both computational fluid dynamics simulations and a model based on resistance analogs proposed in a previous work.
What’s the reality for CDK4/6 inhibitors: Clinical trials or real‐world evidence?
Authors: Trapani Dario , Mayer Erica L.
Published: February 2023

Clinical trials and real‐world evidence (RWE) present conflicting results on the benefit of cyclin‐dependent kinase 4 and 6 inhibitors for patients with advanced hormone receptor–positive and human epidermal growth factor receptor‐2 overexpressing breast cancer. How can RWE be interpreted and used to help guide clinical decisions?
Development and Bioequivalence of 3D‐Printed Medication at the Point‐of‐Care: Bridging the Gap Toward Personalized Medicine
Authors: Lyousoufi Maryam , Lafeber Iris , Kweekel Dinemarie , de Winter Brenda C. M. , Swen Jesse J. , Le Brun Paul P. H. , Bijleveld‐Olierook Erica C. M. , van Gelder Teun , Guchelaar Henk‐Jan , Moes Dirk Jan A. R. , Schimmel Kirsten J. M.
Published: February 2023

Personalized medicine is currently hampered by the lack of flexible drug formulations. Especially for pediatric patients, manual compounding of personalized drug formulations by pharmacists is required. Three‐Dimensional (3D) printing of medicines, which enables small‐scale manufacturing at the point‐of‐care, can fulfill this unmet clinical need. This study investigates the feasibility of developing a 3D‐printed tablet formulation at the point‐of‐care which complies to quality requirements for clinical practice, including bioequivalence. Development, manufacturing, and quality control of the 3D‐printed tablets was performed at the manufacturing facility and laboratory of the department of Clinical Pharmacy and Toxicology at Leiden University Medical Center. Sildenafil was used as a model drug for the tablet formulation. Along with the 3D‐printed tablets a randomized, an open‐label, 2‐period, crossover, single‐dose clinical trial to assess bioequivalence was performed in healthy adults. Bioequivalence was established if areas under the plasma concentration curve from administration to the time of the last quantifiable concentration (AUC0‐t) and maximum plasma concentration (Cmax) ratios were within the limits of 80.00–125.00%. The manufacturing process provided reproducible 3D‐printed tablets that adhered to quality control requirements and were consequently used in the clinical trial. The clinical trial was conducted in 12 healthy volunteers. The 90% confidence intervals (CIs) of both AUC0‐t and Cmax ratios were within bioequivalence limits (AUC0‐t 90% CI: 87.28–104.14; Cmax 90% CI: 80.23–109.58). For the first time, we demonstrate the development of a 3D‐printed tablet formulation at the point‐of‐care that is bioequivalent to its marketed originator. The 3D printing of personalized formulations is a disruptive technology for compounding, bridging the gap toward personalized medicine.
Can corporate social responsibility protect firm value during corporate environmental violation events?
Authors: Ouyang Zhe , Lv Ruixue , Liu Yang
Published: February 2023

This study examines how corporate social responsibility and critical stakeholder (media and analyst) attention affect firm value when an environmental violation occurs. We discover that corporate social responsibility acts as a buffer in influencing firm value by analyzing 224 environmental violation events that occurred in China's publicly traded manufacturing industry firms between 2015 and 2020. Moreover, we find that the corporate social responsibility buffering effect is more substantial when media and analyst attention is high (vs. low). By studying the effects of corporate social responsibility on firm value at the onset of an environmental violation event, this study offers further support for the risk management and reputation insurance theory of corporate social responsibility. It also enriches our understanding of the relationship between corporate social responsibility and financial performance.
Cytologic, histologic, and molecular features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous osteosarcomatous transformation
Authors: Zhang M. Lisa , Sabatino Marlena E. , Castillo Carlos Fernandez‐del , Mattia Anthony R. , Chebib Ivan
Published: February 2023

Fine‐needle aspiration (FNA) is a minimally invasive and effective modality to diagnose pancreatic ductal adenocarcinoma. However, some histologic subtypes of ductal adenocarcinoma are rarely encountered and challenging to diagnose on FNA/small biopsies. To date, cytohistologic features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous elements have not been thoroughly described. An 83‐year‐old man with lower back pain was found to have an incidental pancreatic neck mass. FNA biopsy of the mass showed rare markedly atypical, large, pleomorphic cells in a background of abundant calcifications/bone formation without areas of conventional adenocarcinoma. A diagnosis of “Malignant neoplasm with osteosarcomatous differentiation” was rendered on the FNA specimen. Subsequently, a Whipple resection revealed a 4.1 cm lobulated, calcified pancreatic mass. Microscopic examination showed a heavily calcified/ossified mass with adjacent areas of a highly cellular malignant spindle cell proliferation and admixed large, pleomorphic tumor cells; no background conventional adenocarcinoma was identified. Cytokeratin immunostains MNF116 and CK19 were positive in a large subset of the malignant spindle cells, and AE1.3/CAM5.2 showed patchy weak staining. Molecular testing revealed mutations in KRAS, TP53, BRCA2, NTRK3, EPHA2, MYD88, and CBL. No reportable fusions were detected. The final diagnosis was “Sarcomatoid undifferentiated carcinoma with heterologous elements (osteosarcomatous differentiation).” Definitive diagnosis of extremely rare subtypes of ductal adenocarcinoma is challenging on FNA biopsies. In this case, cytologic evaluation was helpful in making an early diagnosis of a malignant neoplasm with highly unusual features, prompting appropriate triage and early surgical resection of a sarcomatoid undifferentiated carcinoma with prominent osteosarcomatous differentiation.
Similar vegetation‐geomorphic disturbance feedbacks shape unstable glacier forelands across mountain regions
Authors: Eichel Jana , Draebing Daniel , Winkler Stefan , Meyer Nele
Published: February 2023

Glacier forelands are among the most rapidly changing landscapes on Earth. Stable ground is rare as geomorphic processes move sediments across large areas of glacier forelands for decades to centuries following glacier retreat. Yet, most ecological studies sample exclusively on stable terrain to fulfill chronosequence criteria, thus missing potential feedbacks between geomorphic disturbances and vegetation colonization. By influencing vegetation and soil development, such vegetation‐geomorphic disturbance feedbacks could be crucial to understand glacier foreland ecosystem development in a changing climate. We surveyed vegetation and environmental properties, including geomorphic disturbance intensities, in 105 plots located on both stable and unstable moraine terrain in two geomorphologically active glacier forelands in New Zealand and Switzerland. Our plot data showed that geomorphic disturbance intensities permanently changed from high/moderate to low/stable when vegetation reached cover values of around 40%. Around this cover value, species with response and effect traits adapted to geomorphic disturbances dominated. This suggests that such species can act as “biogeomorphic” ecosystem engineers that stabilize ground through positive feedback loops. Across floristic regions, biogeomorphic ecosystem engineer traits creating ground stabilization, such as mat growth and association with mycorrhiza, are remarkably similar. Nonmetric multidimensional scaling revealed a linked sequence of decreasing geomorphic disturbance intensities and changing species composition from pioneer to late successional species. We interpret this linked geomorphic disturbance‐vegetation succession sequence as “biogeomorphic succession,” a common successional pathway in unstable river and coastal ecosystems across the world. Soil and vegetation development were related to this sequence and only advanced once biogeomorphic ecosystem engineer species covered 40%–45% of a plot, indicating a crucial role of biogeomorphic ecosystem engineer stabilization. Different topoclimatic conditions could explain variance in biogeomorphic succession timescales and ecosystem engineer root traits between the glacier forelands. As glacier foreland ground is widely unstable, we propose to consider glacier forelands as “biogeomorphic ecosystems” in which ecosystem structure and function are shaped by geomorphic disturbances and their feedbacks with adapted plant species, similar to rivers and coasts.
Long‐term patterns in ecosystem phenology near Palmer Station, Antarctica, from the perspective of the Adélie penguin
Authors: Cimino Megan A. , Conroy John A. , Connors Elizabeth , Bowman Jeff , Corso Andrew , Ducklow Hugh , Fraser William , Friedlaender Ari , Kim Heather Hyewon , Larsen Gregory D. , Moffat Carlos , Nichols Ross , Pallin Logan , Patterson‐Fraser Donna , Roberts Darren , Roberts Megan , Steinberg Deborah K. , Thibodeau Patricia , Trinh Rebecca , Schofield Oscar , Stammerjohn Sharon
Published: February 2023

Climate change is leading to phenological shifts across a wide range of species globally. Polar oceans are hotspots of rapid climate change where sea ice dynamics structure ecosystems and organismal life cycles are attuned to ice seasonality. To anticipate climate change impacts on populations and ecosystem services, it is critical to understand ecosystem phenology to determine species activity patterns, optimal environmental windows for processes like reproduction, and the ramifications of ecological mismatches. Since 1991, the Palmer Antarctica Long‐Term Ecological Research (LTER) program has monitored seasonal dynamics near Palmer Station. Here, we review the species that occupy this region as year‐round residents, seasonal breeders, or periodic visitors. We show that sea ice retreat and increasing photoperiod in the spring trigger a sequence of events from mid‐November to mid‐February, including Adélie penguin clutch initiation, snow melt, calm conditions (low winds and warm air/sea temperature), phytoplankton blooms, shallow mixed layer depths, particulate organic carbon flux, peak humpback whale abundances, nutrient drawdown, and bacterial accumulation. Subsequently, from May to June, snow accumulates, zooplankton indicator species appear, and sea ice advances. The standard deviation in the timing of most events ranged from ~20 to 45 days, which was striking compared with Adélie penguin clutch initiation that varied <1 week. In general, during late sea ice retreat years, events happened later (~5 to >30 days) than mean dates and the variability in timing was low (<20%) compared with early ice retreat years. Statistical models showed the timing of some events were informative predictors (but not sole drivers) of other events. From an Adélie penguin perspective, earlier sea ice retreat and shifts in the timing of suitable conditions or prey characteristics could lead to mismatches, or asynchronies, that ultimately influence chick survival via their mass at fledging. However, more work is needed to understand how phenological shifts affect chick thermoregulatory costs and the abundance, availability, and energy content of key prey species, which support chick growth and survival. While we did not detect many long‐term phenological trends, we expect that when sea ice trends become significant within our LTER time series, phenological trends and negative effects from ecological mismatches will follow.
Multidynamic Crystalline Molecular Rotors Comprising an N‐Heterocyclic Carbene Binuclear Au(I) Complex Bearing Multiple Rotators
Authors: Jin Mingoo , Matsuura Satsuki , Yamamoto Hikaru , Mizuno Motohiro , Ito Hajime
Published: February 2023

We report multidynamic molecular rotations in crystals using a concave‐shape N‐heterocyclic carbene (NHC) binuclear Au(I) complex rotor bearing pyrazine and tetrahydrofuran (THF) molecules as multicomponent rotators. Single‐crystal X‐ray diffraction (XRD) measurements revealed that two THF molecules are located near the central pyrazine encapsulated by two bulky NHC ligands. From 2H solid‐state NMR analysis, it was observed that the pyrazine rotated in a 2‐fold site exchange with a 180° rotational angle and a 31 kJ mol−1 energy barrier, while the THF molecules showed a 23°‐38° libration with a lower energy barrier (14 kJ mol−1). Interestingly, the pyrazine rotation was accelerated when the THF molecules rotated in fast site exchange with a large angle of libration, suggesting that the rotators exhibit multidynamics in a correlated manner.
A comprehensive cognition for the capacity fading mechanism of FeS2 in argyrodite‐based all‐solid‐state lithium battery
Authors: Wu Zhan , Zhang Wenkui , Xia Yang , Huang Hui , Gan Yongping , He Xinping , Xia Xinhui , Zhang Jun
Published: February 2023

Sulfide solid state electrolyte (SSE) possesses high ionic conductivity and great processability but suffers from narrow electrochemical window. Conversion sulfide cathode FeS2 has higher specific capacity and moderate redox potential, making it appropriate toward sulfide SSE. However, the complex reaction pathway and capacity fading mechanism in FeS2 are rarely studied, especially in all‐solid‐state lithium battery (ASSLB). Herein, argyrodite sulfide SSE is paired with FeS2 to investigate the electrochemical reaction pathways and the capacity fade mechanism. Instead of single conversion reaction, an anionic redox driven reaction of FeS2 is revealed. The oxidization of Li2S vanishes and large quantity of inactive Li2S accumulates to cause the interfacial deterioration, along with the stress concentration during cycling, which leads to the rapid capacity fade of FeS2. Finally, a simple strategy of slurry‐coated composite electrode with highly conductive network is proposed to direct the uniform deposition of Li2S and alleviate the stress concentration.

image
Nutritional assessment models for Alzheimer's disease: Advances and perspectives
Authors: Wen Yuxi , Zhang Lizhu , Li Na , Tong Aijun , Zhao Chao
Published: February 2023

Alzheimer's disease (AD) is a neurodegenerative disease of uncertain pathogenesis that develops in the elderly population and is characterized by loss of cognitive function, memory loss, and deterioration of everyday behavior. The development of biological models of AD is constrained by the complexity of the pathogenesis and multiple causes. Creating disease models can aid in understanding the pathophysiology of AD and developing effective therapeutic drugs. In this review, the animal and cellular models that are currently being utilized to research AD are outlined and described in detail according to modeling approaches. The main animal models are natural aging models, transgenic models, and drug‐induced models. The main cellular models are traditional 2D cells, human induced pluripotent stem 2D cells (neurons and glial cells), and 3D cells, as well as organoid models, and the benefits and drawbacks of their various biological models are assessed. They do have their limitations due to an incomplete reflection of AD pathology. Therefore, new models for AD research are needed in the future. The summary of existing models is intended to provide a basis for the subsequent development of new disease models and to provide a reference for the study of disease mechanisms, clinical research, and new drug development in AD.
Does herding effect help forecast market volatility?—Evidence from the Chinese stock market
Authors: Wang Yide , Yu Chao , Zhao Xujie
Published: February 2023

This paper aims to study the predictive power of market herding effect for market volatility. We extend the widely used four types of linear HAR models by incorporating the market herding index and further introduce a nonlinear forecasting mechanism by using two machine learning algorithms—support vector regression (SVR) and random forest (RF). All the methods are applied to the Chinese stock market. We evaluate their in‐sample and out‐of‐sample performances for various prediction step lengths. The results show that according to the RMSE and MAE, for the daily volatility prediction, the extra herding factor makes no significant contribution, and the linear model has no significant difference with the algorithms as well, whereas with the increase of step length, the herding factor shows a significant power in the weekly, monthly, and quarterly prediction, and meanwhile, the RF algorithm outperforms the other methods. However, for the QLIKE, the herding factor always significantly improves the predictions for all kinds of step lengths and methods, and the SVR algorithm with the herding factor is dominant. Overall, the herding factor helps forecast the volatility, and the extent to which the precision is improved takes on an inverted “U” shape with the increase in step length. The two algorithms are superior to the linear model, especially for the longer‐term prediction, and the herding factor can help enlarge this advantage, which implies a nonlinear relationship between the herding and volatility. Besides, the extra liquidity factor plays no significant role in the volatility prediction, but the continuous variation (CV), jump variation (JV), and leverage effect are helpful in most cases.
Studying the microbial, chemical, and sensory characteristics of shrimp coated with alginate sodium nanoparticles containing Zataria multiflora and Cuminum cyminum essential oils
Authors: Osanloo Mahmoud , Eskandari Zahra , Zarenezhad Elham , Qasemi Hajar , Nematollahi Amene
Published: February 2023

Retardation of quality loss of seafood has been a new concept in recent years. This study's main objective was to evaluate the microbial, chemical, and sensory attributes of shrimp coated with alginate sodium nanoparticles containing Zataria multiflora and Cuminum cyminum essential oils (EOs) during refrigerated storage. At the end of storage time (15 days storage at 4°C), the pH, thiobarbituric acid reactive substances (TBARS), and total volatile basic nitrogen (TVBN) amounts in shrimps coated with the alginate nanoparticles were 7.62, 1.14 mg MDA/kg, and 117 mg/100 g which were significantly (p < .05) lower than the control groups. The count of all bacteria groups was also lower in this treatment, which was 2–2.74 Log CFU/mL on day 15 of cold storage. This combined treatment also obtained the highest sensory scores (around 7) and the lowest melanosis score (2.67) due to the effective delaying microbial and oxidation activities. Therefore, this edible coating could substantially retard microbial and chemical changes and improve the organoleptic properties of shrimp under refrigerated storage.
Transient receptor potential Ankyrin‐1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices
Authors: Giacco Vincenzo , Flower Grace , Artamonova Maria , Hunter Jake , Padilla Requerey Aitana , Hamilton Nicola B.
Published: February 2023

Oligodendrocytes are highly specialized glial cells characterized by their production of multilayer myelin sheaths that wrap axons to speed up action potential propagation. It is due to their specific role in supporting axons that impairment of myelin structure and function leads to debilitating symptoms in a wide range of degenerative diseases, including Multiple Sclerosis and Leukodystrophies. It is known that myelin damage can be receptor‐mediated and recently oligodendrocytes have been shown to express Ca2+‐permeable Transient Receptor Potential Ankyrin‐1 (TRPA1) channels, whose activation can result in myelin damage in ischemia. Here, we show, using organotypic cortical slice cultures, that TRPA1 activation, by TRPA1 agonists JT010 and Carvacrol for varying lengths of time, induces myelin damage. Although TRPA1 activation does not appear to affect oligodendrocyte progenitor cell number or proliferation, it prevents myelin formation and after myelination causes internodal shrinking and significant myelin degradation. This does not occur when the TRPA1 antagonist, A967079, is also applied. Of note is that when TRPA1 agonists are applied for either 24 h, 3 days or 7 days, axon integrity appears to be preserved while mature myelinated oligodendrocytes remain but with significantly shortened internodes. These results provide further evidence that TRPA1 inhibition could be protective in demyelination diseases and a promising therapy to prevent demyelination and promote remyelination.
Predictors of ibrutinib‐associated atrial fibrillation: 5‐year follow‐up of a prospective study
Authors: Mattiello Veronica , Barone Angelica , Giannarelli Diana , Noto Alessandro , Cecchi Nicola , Rampi Nicolò , Cassin Ramona , Reda Gianluigi
Published: February 2023

Ibrutinib‐associated atrial fibrillation (IRAF) emerged among the adverse events of major interests in ibrutinib‐treated patients as real‐world studies showed a higher incidence compared to clinical trials. We prospectively analyzed predictors of IRAF in 43 single‐center consecutive patients affected by chronic lymphocytic leukemia that started therapy with ibrutinib between 2015 and 2017. Key secondary endpoints were to describe the management of IRAF and survival outcomes. During a median follow‐up period of 52 months, we registered 45 CV events, with a total of 23 AF events in 13 patients (CI 30.0% (95% CI: 16.5–43.9)). Pre‐existent cardiovascular risk factors, in particular hypertension, a previous history of AF and a high Shanafelt risk score emerged as predictors of IRAF. Baseline echocardiographic evaluation of left atrial (LA) dimensions confirmed to predict IRAF occurrence and cut‐off values were identified in our cohort: 32 mm for LA diameter and 18 cm2 for LA area. No difference in progression free survival and overall survival emerged in patients experiencing IRAF. Following AF, anticoagulation was started in all eligible patients, and cardioactive therapy was accordingly modified. Echocardiography represents a highly reproducible and widespread tool to be included in the work‐up of ibrutinib candidates; the identification of IRAF predictors represents a useful guide to clinical practice.
Seasonal dynamics of canopy interception loss within a deciduous and a coniferous forest
Authors: Andreasen Mie , Christiansen Jesper R. , Sonnenborg Torben O. , Stisen Simon , Looms Majken C.
Published: February 2023

Canopy interception loss is a key process in forest hydrology and the role of interception loss in relation to the forest water budgets and future impact of afforestation on water resources is important to quantify. Based on high frequency in situ monitoring, the effect of species‐ and leaf‐cover‐specific canopy structure metrics for interception loss estimation is examined at the two most typical forest types in Denmark. First, interception loss is estimated from precipitation and throughfall data collected in two even‐aged (40–60 years) temperate oak (deciduous) and Norway spruce (coniferous) forests over 13 and 11 months, respectively. Second, based on these observations we estimated canopy structure parameters relevant for interception loss; direct throughfall (ρ), the precipitation necessary to saturate the canopy (P'), the canopy evaporation as a fraction of precipitation (EC/P) and canopy storage capacity (S). Third, we compare observation‐based interception loss with predictions obtained by the analytical Gash interception model using the derived canopy structure parameters. Lastly, the effect of species‐ and leaf‐cover on the interception loss is quantified by applying the canopy structure parameters of the deciduous and coniferous forest on the same daily precipitation data set of approximately 1 year in the Gash model. We found that the derived canopy structure parameters reflect the seasonal change in the leaf cover of the deciduous forest and different parameters are identified for the two forest types. In the deciduous forest, improved agreement between observation‐based and predicted interception loss is obtained using canopy structure parameters for the leafless and full‐foliage periods instead of annual average values. The share of throughfall and interception loss to precipitation (total sum of precipitation = 526 mm) is 65% (340 mm) and 35% (186 mm) for the deciduous forest, respectively, and 49% (260 mm) and 51% (266 mm) for the coniferous forest, respectively. A seasonal variation of interception loss is observed in the deciduous forest where the share of interception loss to precipitation is 40% during the period with leaves on the trees (June to November) and 22% for the leafless periods (December to May). Thus, species‐ and leaf‐cover‐specific canopy structure metrics enhance model performance of throughfall and interception loss dynamics in forests.
Association of inflammatory bowel disease in first‐degree relatives with risk of colorectal cancer: A nationwide case‐control study in Sweden
Authors: Wang Kai , Olén Ola , Emilsson Louise , Khalili Hamed , Halfvarson Jonas , Song Mingyang , Ludvigsson Jonas F.
Published: February 2023

This study aims to assess the association between inflammatory bowel disease (IBD) history in first‐degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case‐control study in Sweden among 69 659 CRC cases and 343 032 non‐CRC controls matched on age, sex, birth year and residence county. Through linkage of multi‐generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91‐1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18‐39, 40‐59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early‐onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.
Personal freedom, family compositions and well‐being
Authors: Noguchi Kenji
Published: February 2023

Personal freedom has known to be positively associated with well‐being. As socioeconomic conditions advanced in modern societies, the pursuit of personal freedom has also gradually increased. This trend further coincides with the decline in marriage and fertility rates. This implies that the pursuit of personal freedom could be related to lower involvement with the family. The current study examined how personal freedom would be related to family compositions and well‐being across different socioeconomic conditions using a large‐scale data set. The results indicated that personal freedom was the most consistent predictor of well‐being. Marriage‐like relationships were also positively related to well‐being. However, the relationship between the number of children and well‐being was mostly insignificant except for the most recent data showing a positive relationship. Results also indicated that personal freedom did not lead to singlehood but was negatively related to the number of children. Socioeconomic conditions of countries and different time periods moderated these relationships. The influences of different socioeconomic conditions and the time period were discussed further in the paper.
Security in IoT systems using natural language processing: Future challenges and directions
Authors: Kumar Yogendra , Kumar Vijay
Published: February 2023

The internet of things (IoT) is advancing human lives by providing various intelligent services. The advancement of cutting‐edge technologies necessitates an increase in the need for cyber security. In this light, an extensive research has been conducted to address IoT security concerns. However, several security challenges must be addressed before IoT can be utilized to its full potential in real‐time. Motivated by this fact, this study presents a novel integration approach of Natural Language Processing (NLP) with IoT systems to enhance its security. It investigates the current state of NLP and its applications. The key contribution of this paper is the development of a system for identifying malicious behaviors in an IoT environment using n‐gram and word‐embedding techniques. Several security challenges and possible future directions to enhance IoT security using NLP are also addressed in this study.
NADPH oxidase 4 regulate the glycolytic metabolic reprogramming of microglial cells to promote M1 polarization
Authors: Zhai Liping , Ruan Shuiliang , Wang Jin , Guan Qiaobing , Zha Li
Published: February 2023

This work aimed to investigate the role and mechanism of NADPH oxidase 4 (NOX4) in the polarization of microglial cells. Microglial cells were transfected with the NOX4 overexpression plasmid (pGL3‐NOX4), and later treated with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ) to induce its M1 polarization. Later, the F4/80 + CD86 + cell proportion was detected by flow cytometry (FCM), the inflammatory factor expression levels were analyzed through enzyme‐linked immunosorbent assay (ELISA), while ionized calcium binding adapter molecule 1 (IBA‐1) and PKM2 expression were measured by immunofluorescence (IF) staining. In addition, dichlorodihydrofluorescein diacetate probe was utilized to detect the reactive oxygen species (ROS) levels, glucose uptake, and glycolysis, as well as lactic acid level. The expression of glycolytic enzymes PKM2, HK2, and citrate (Si)‐synthas (CS) was detected by Western‐blot (WB) assay. Moreover, the polarization level of microglial cells was detected after ROS expression was suppressed by the ROS inhibitor N‐acetylcysteine (NAC). In mouse experiments, LPS was applied in inducing central neuroinflammation in NOX4 knockdown mouse model (KO) and wild‐type mice (WT). Thereafter, the inflammatory factor levels and lactic acid level in mouse tissues were detected; IBA‐1 and CD86 expression in mice was measured by IF staining; and the expression of glycolytic enzymes PKM2, HK2, and CS in the central nervous system (CNS) was also detected. After NOX4 overexpression in microglial cells, the M1 polarization level was upregulated, the F4/80 + CD86 + cell proportion increased, and inflammatory factors were upregulated. At the same time, the expression of glycolytic enzymes PKM2, HK2, and CS was upregulated. NAC pretreatment suppressed the effects of NOX4, reduced the F4/80 + CD86 + cell proportion, and suppressed the expression of PKM2, HK2, and CS. In the mouse model, the expression levels of CD86 in KO group decreased, and the inflammatory factors were also downregulated. NOX4 promotes glycolysis of microglial cells via ROS, thus accelerating M1 polarization and inflammatory factor expression. In this regard, NOX4 is promising as a new target for the treatment of neuroinflammation.
A nomogram prediction of citrate reaction during mononuclear cell collection in solid tumor patients
Authors: Xia Yong , Xue Hui , Li Jing , Yu Yanyan , Huang Wei , Zhou Chuchu , Shi Tingting , Cheng Yanxia , Zhang Caihong , Liu Shuang , Song Zongchang , Xu Sha , Lou Jinxing
Published: February 2023

Purpose

Citrate reaction is one of the main adverse events in peripheral blood mononuclear cell (MNC) collection. The aim of this study was to elucidate the risk factors for citrate reaction in patients with advanced solid tumor collection and to construct a nomogram to predict the risk.

Methods

One hundred forty‐eight patients with advanced solid tumor who underwent peripheral blood MNC collection in our hospital between January 2021 to December 2021 were selected. The general data, creatinine level before collection, Ca2+ concentration before collection, absolute value of monocyte lymphocytes before collection, circulating blood volume, anticoagulant dosage, and blood collection duration were included in Logistic regression analysis to identify the risk factors of citrate reaction. According to the results of the multivariate logistic model, nomogram was established and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model.

Results

Among the 148 solid tumor patients, 35 patients (23.6%) of the 148 patients developed citrate reaction. Multivariate analysis showed that the risk factors for citrate reaction in the process of collection included sex (odds ratio [OR] = 6.718; 95% confidence interval [95% CI]: 2.191‐20.594, P = .001), age (OR = 0.957; 95% CI: 0.921‐0.996, P = .03), and processed circulating blood volume (OR = 1.001; 95% CI: 1.000‐1.002, P = .01). Logistic regression can analyze independent risk factors and establish risk prediction model. The predictive performance of the model is good, and the area under ROC curve is 0.799.

Conclusions

The MNC collection process is safe. The incidence of citrate reaction in the collection of peripheral blood MNCs from patients with advanced solid tumor is related to the age, gender, and processed circulating blood volume of patients. The nomogram can be used to assess a patient's risk of citrate reaction.
How economic system justification shapes demand for peer‐to‐peer providers
Authors: Cakanlar Aylin , Ordabayeva Nailya
Published: February 2023

With the proliferation of peer‐to‐peer (P2P) exchanges in the marketplace, understanding which consumer factors drive demand for P2P providers is important. We examine the role of consumers' economic system justification (ESJ) beliefs (about the fairness of existing economic arrangements and outcomes), which, despite their growing salience in the marketplace, have been overlooked in extant P2P research. We show that high (vs. low) ESJ increases consumers' interest in purchasing from P2P providers because it heightens perceptions of these providers' entrepreneurial spirit. The effect emerges in the laboratory and in the field with measured and manipulated ESJ, and it is attenuated for traditional commercial providers. The findings offer novel insights and implications for practice and emerging research on P2P exchanges, system justification, and ideological consumption more broadly.
Molecular mechanisms of post‐burn muscle wasting and the therapeutic potential of physical exercise
Authors: Dombrecht Dorien , Van Daele Ulrike , Van Asbroeck Birgit , Schieffelers David , Guns Pieter‐Jan , Gebruers Nick , Meirte Jill , van Breda Eric
Published: February 2023

After a severe burn injury, a systemic stress response activates metabolic and inflammatory derangements that, among other, leads to muscle mass loss (muscle wasting). These negative effects on skeletal muscle continue for several months or years and are aggravated by short‐term and long‐term disuse. The dynamic balance between muscle protein synthesis and muscle protein breakdown (proteolysis) is regulated by complex signalling pathways that leads to an overall negative protein balance in skeletal muscle after a burn injury. Research concerning these molecular mechanisms is still scarce and inconclusive, understanding of which, if any, molecular mechanisms contribute to muscle wasting is of fundamental importance in designing of therapeutic interventions for burn patients as well. This review not only summarizes our present knowledge of the molecular mechanisms that underpin muscle protein balance but also summarizes the effects of exercise on muscle wasting post‐burn as promising strategy to counteract the detrimental effects on skeletal muscle. Future research focusing on the pathways causing post‐burn muscle wasting and the different effects of exercise on them is needed to confirm this hypothesis and to lay the foundation of therapeutic strategies.
A compendium of single extracellular vesicle flow cytometry
Authors: Welsh Joshua A. , Arkesteijn Ger J. A. , Bremer Michel , Cimorelli Michael , Dignat‐George Françoise , Giebel Bernd , Görgens André , Hendrix An , Kuiper Martine , Lacroix Romaric , Lannigan Joanne , van Leeuwen Ton G. , Lozano‐Andrés Estefanía , Rao Shoaib , Robert Stéphane , de Rond Leonie , Tang Vera A. , Tertel Tobias , Yan Xiaomei , Wauben Marca H. M. , Nolan John P. , Jones Jennifer C. , Nieuwland Rienk , van der Pol Edwin
Published: February 2023

Flow cytometry (FCM) offers a multiparametric technology capable of characterizing single extracellular vesicles (EVs). However, most flow cytometers are designed to detect cells, which are larger than EVs. Whereas cells exceed the background noise, signals originating from EVs partly overlap with the background noise, thereby making EVs more difficult to detect than cells. This technical mismatch together with complexity of EV‐containing fluids causes limitations and challenges with conducting, interpreting and reproducing EV FCM experiments. To address and overcome these challenges, researchers from the International Society for Extracellular Vesicles (ISEV), International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH) joined forces and initiated the EV FCM working group.

To improve the interpretation, reporting, and reproducibility of future EV FCM data, the EV FCM working group published an ISEV position manuscript outlining a framework of minimum information that should be reported about an FCM experiment on single EVs (MIFlowCyt‐EV). However, the framework contains limited background information. Therefore, the goal of this compendium is to provide the background information necessary to design and conduct reproducible EV FCM experiments. This compendium contains background information on EVs, the interaction between light and EVs, FCM hardware, experimental design and preanalytical procedures, sample preparation, assay controls, instrument data acquisition and calibration, EV characterization, and data reporting. Although this compendium focuses on EVs, many concepts and explanations could also be applied to FCM detection of other particles within the EV size range, such as bacteria, lipoprotein particles, milk fat globules, and viruses.
Characterization of Microvascular Invasion in Hepatocellular Carcinoma Using Computational Modeling of Interstitial Fluid Pressure and Velocity
Authors: Zheng Liyun , Yang Chun , Sheng Ruofan , Rao Shengxiang , Wu Lifang , Zeng Mengsu , Dai Yongming
Published: February 2023

Background

Most solid tumors show increased interstitial fluid pressure (IFP), and this increased IFP is an obstacle to treatment. A noninvasive model for measuring IFP in hepatocellular carcinoma (HCC) is an unresolved issue.

Purpose

To develop a noninvasive model to measure IFP and interstitial fluid velocity (IFV) in HCC and to characterize the microvascular invasion (MVI) status by using this model.

Study Type

Retrospective.

Population

A total of 97 HCC patients (mean age 57.6 ± 10.9 years, 77.3% males), 53 of them with MVI and 44 of them without MVI.

Field Strength/Sequence

A 3‐T, three‐dimensional spoiled gradient‐recalled echo.

Assessment

MVI was defined as microscopic vascular invasion of small vessels within the peritumoral liver tissue. The volumes of interest (VOIs) were manually delineated and enclosed the tumor lesion and healthy liver parenchyma, respectively. The extended Tofts model (ETM) was used to estimate permeability parameters from all the VOIs. Subsequently, the continuity partial differential equation (PDE) was implemented and IFP and IFV were acquired.

Statistical Tests

Wilcoxon signed‐ranks tests, histogram analysis, Mann–Whitney U test, Fisher's exact test, least absolute shrinkage and selection operator (LASSO) logistic regression, receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC), Youden index, DeLong test, and Benjamini–Hochberg correction. A P value <0.05 was considered statistically significant.

Results

The HCC lesions exhibited elevated IFP and reduced IFV. There were no significant differences in any measured demographic and clinical features between the MVI‐positive and MVI‐negative groups, except for tumor size. Nine IFP histogram analysis‐derived parameters and seven IFV histogram analysis‐derived parameters could be used to characterize the MVI status. LASSO regression selected five features: IFP maximum, IFP 10th percentile, IFP 90th percentile, IFV SD, and IFV 10th percentile. The combination of these features showed the highest AUC (0.781) and specificity (77.3%).

Data Conclusion

A noninvasive IFP and IFV measurement model for HCC was developed. Specific IFP‐ and IFV‐derived parameters exhibited significant association with the MVI status.

Evidence Level

3.

Technical Efficacy

Stage 2.
Influence of Kamchatka Blocking and East Asian winter monsoon on the winter 2m‐temperature over South Korea
Authors: Choi Myeong‐Ju , Ahn Joong‐Bae
Published: February 2023

This study examines the factors affecting the 2m‐temperatures (T2m) in South Korea in winter (DJF) from 1979/1980 to 2018/2019. For this purpose, we performed an empirical orthogonal function (EOF) analysis of the geopotential height at 500 hPa in the region 15°–75°N, 70°E–180° centred around the Korean Peninsula. The first EOF mode, which accounted for 31.1% of the total variance of the winter T2m in the region, is related to the KamChatka Blocking Frequency (KCBF). The second mode, which accounted for 18.3%, is associated with East Asian winter monsoon (EAWM). In addition to EOF analysis, the partial correlation (PC) analysis also confirmed that KCBF Index and EAWM Index, which are highly correlated with the winter T2ms in South Korea, are independent of each other. The individual and combined effects of the KCBF and EAWM are examined because they independently affect the winter T2ms in South Korea. According to the composite analysis, in the years when KCBF is higher than normal (H_KCBF), negative and positive Z500 anomalies are located over the south Sea of Japan and the Kamchatka Peninsula, respectively. In other words, the positive geopotential anomaly over the Kamchatka Peninsula lowers the T2ms of South Korea by blocking the flow of cold air moving eastward from the Korean Peninsula. In the years when a strong EAWM occurred (S_EAWM), negative and positive Z500 anomalies are located over the Manchuria region and the northwestern regions of Russia, respectively. Consequently, cold air in the north moves southward, resulting in lower T2ms in South Korea. For the combined effects of KCBF and EAWM on the T2ms, winters of 40 years are categorized into L_KCBF‐W_EAWM, L_KCBF‐S_EAWM, H_KCBF‐W_EAWM and H_KCBF‐S_EAWM years. The analyses show that when KCBF and EAWM are in phase, the T2ms in South Korea are more prominent than when they are out‐of‐phase.
Comparison of hermetic bags with polyethylene‐lined polypropylene bags for prolonged storage of faba bean (Vicia faba L.) seeds in Ethiopia
Authors: Seifu Astawus Esatu , Kalsa Karta Kaske , Aweke Hasen Seid , Dibaba Girma Debele
Published: February 2023

Poor storage facilities expose seeds to deterioration, resulting in low seed quality under a prolonged storage time. We compared the performance of five bag types: Two hermetic bags (Super GrainPro bag [SGB] and Purdue Improved Crop Storage bag [PICS]), with three non‐hermetic bags (woven polypropylene bag lined with polyethylene [WPP lined with PE], polypropylene bags [PP], and jute bags) for the storage of faba bean seeds for 24 months. Faba bean seed quality was assessed under ambient conditions after 0, 6, 12, 18, and 24 months of storage. Parameters investigated include seed moisture content, thousand seed weight, germination percentages, vigor index I and II, speed of germination, percentage of insect‐damaged seed, and insect counts. Results indicated that there was a significant (P ≤ 0.01) interaction of bag types and duration for all tested parameters. Hermetic bags and WPP lined with PE maintained germination percentage above 90% during 12 months of storage. The vigor index remained above 1600 mg% for hermetic bags and WPP lined with PE during 12 months of storage. However, non‐hermetic bags exhibited a rapid drop in vigor index beginning from 6 months of storage. Hermetic bags and WPP lined with PE allowed minimal insect breeding and hence decreased the seed damage caused by insects. The present results demonstrated that in addition to the PICS bags and SGB, the WPP lined with PE can be used for short‐period storage for up to 12 months without incurring a significant loss of seed quality. Hence, we recommend the introduction of WPP lined with PE as faba bean seed storage technique under conditions where hermetic bags are inaccessible to resource‐poor farmers.
Morbidity Milestones Demonstrate Long Disability‐Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus
Authors: Schnalke Nils , Konitsioti Agni , Frank Anika , Kurz Martin , Polanski Witold H. , Themann Peter , Wolz Martin , Sobottka Stephan B. , Reichmann Heinz , Falkenburger Bjoern , Klingelhoefer Lisa
Published: February 2023

Background

Deep brain stimulation of the subthalamic nucleus (STN‐DBS) is an effective treatment for Parkinson's disease (PD). The long‐term benefit in PD patients with STN‐DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively.

Objectives

To judge the long‐term outcome of patients with STN‐DBS.

Methods

To assess the evolution of PD symptoms and health‐related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross‐sectional analysis of 115 patients with STN‐DBS with rater‐based scales and self‐reported questionnaires. In addition, we screened records of all our STN‐DBS patients (2001–2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability‐free life expectancy.

Results

In the first year of STN‐DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN‐DBS.

Conclusions

On average, PD patients with STN‐DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN‐DBS.