bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Different Land Use Scenarios on Future Global and Regional Climate Extremes
Authors: Hong Tao , Wu Junjie , Kang Xianbiao , Yuan Min , Duan Lian
Published: June 2022

Land use and land cover change (LULCC) alters the character of the land surface and directly impacts the climate. The impacts of LULCC on historical and future climate have been largely investigated, mostly using simulations with or without land use change. However, it is still not clear to what extent the projections of future climate change depend on the choice of land use scenario, which can provide important guidance on using land use and land management as a tool for regional climate mitigation. Here, using ten Earth system models participating in future land use policy sensitivity experiments in Land Use Model Intercomparison Project (LUMIP), we assessed the impact of two different land use scenarios (SSP1-2.6 and SSP3-7.0) on extreme climate. The results demonstrate that the use of different land use change scenarios has a substantial effect on the projections of regional climate extreme changes. Our study also reveals that, compared with other anthropogenic forcings, land use change has a considerable contribution to regional temperature extreme changes, with the contribution ranging from −14.0% to 10.3%, and the contribution to regional precipitation extreme change is larger, with a range of −118.4~138.8%. The global climate effects of land use change are smaller in magnitude than regional effects, with a small (5%) contribution to temperature extreme change. We also found a large spread in the model’s responses to LULCC, especially for precipitation extremes, suggesting that observation-based studies on reducing models’ uncertainties are needed to obtain more robust future projections of regional climate change. Our study highlights the essential role of land use and land management strategies in future regional climate mitigation.
Impacts of the Interannual Variability of the Kuroshio Extension on the East Asian Trough in Winter
Authors: Sun Jianxiang , Zhang Suping , Jiang Yuxi , Wang Yanshuo , Wu Baoqin , Wang Haijiao
Published: June 2022

The responses of the East Asian Trough (EAT) to the Kuroshio Extension (KE) interannual fluctuation and the underlying mechanisms in the boreal winter are investigated through the lag regression approach in this study. When the KE is in the stable state, the sea surface temperature (SST) front is strengthened, with cold (warm) SST anomaly in the western (eastern) region of the KE, releasing less (more) heat into the atmosphere. The opposite patterns hold for the KE unstable periods. The analysis of the observations shows that the stable KE corresponds to a deeper EAT, accompanied with a stronger winter monsoon over Mongolia and northeastern China. The atmospheric Rossby waves, transient eddies, and thermal winds are found to be responsible for this relationship between the KE and EAT. The SST warming in the lower reaches of the KE excites the Rossby wave activity that propagates toward East Asia, leading to 25% of the EAT amplification. Meanwhile, influenced by the KE-induced Rossby waves, the background baroclinicity is intensified over Japan, which enhances the transient eddy activity, contributing to another 42% magnitude of the EAT deepening. In addition, as depicted by the thermal wind theory, the strong SST cooling in the upper branch of the KE forces an anomalous cyclonic circulation through modifying the meridional temperature gradient, facilitating the EAT development. The finding points to the better understandings of the EAT and associated East Asian winter climate variability, which are crucial for their major economic and social impacts on the large populations in the region.
On the Wigner-Kirkwood Expansion of the Free Energy and the Evaluation of the Quantum Correction
Authors: Kazandjian Luc , Soubiran François , Pain Jean-Christophe
Published: June 2022

The Wigner-Kirkwood expansion of the quantum correction to the classical free energy is generally said to be in powers of ℏ2 and only its first few terms are presented. In this work, we use the Bloch differential equation to obtain a general description of all terms in a dimensionless form. The first corrective term turns out to be proportional to the product of λ2/a2, where λ is the thermal de Broglie wavelength and a3 is the volume per particle, by an effective coupling constant. This dimensionless parameter can be used to assess the magnitude of the quantum correction. Using the one-component plasma as an illustration we highlight the importance of the magnitude of the potential on the quantum correction. The results presented are not formally new; the emphasis is placed on a simple and didactic presentation.
Lateralization Pattern of the Weber Tuning Fork Test in Longstanding Unilateral Profound Hearing Loss: Implications for Cochlear Implantation
Authors: Bassiouni Mohamed , Häußler Sophia Marie , Gräbel Stefan , Szczepek Agnieszka J. , Olze Heidi
Published: June 2022

The Weber tuning fork test is a standard otologic examination tool in patients with unilateral hearing loss. Sound should typically lateralize to the contralateral side in unilateral sensorineural hearing loss. The observation that the Weber test does not lateralize in some patients with longstanding unilateral deafness has been previously described but remains poorly understood. In the present study, we conducted a retrospective analysis of the medical records of patients with unilateral profound hearing loss (single-sided deafness or asymmetric hearing loss) for at least ten years. In this patient cohort, childhood-onset unilateral profound hearing loss was significantly associated with the lack of lateralization of the Weber tuning fork test (Fisher’s exact test, p < 0.05) and the absence of tinnitus in the affected ear (Fisher’s exact test, p < 0.001). The findings may imply a central adaptation process due to chronic unilateral auditory deprivation starting before the critical period of auditory maturation. This notion may partially explain the poor outcome of adult cochlear implantation in longstanding single-sided deafness. The findings may suggest a role for the Weber test as a simple, quick, and economical tool for screening poor cochlear implant candidates, thus potentially supporting the decision-making and counseling of patients with longstanding single-sided deafness.
Context-Free Grammars for Several Triangular Arrays
Authors: Zhou Roberta Rui , Yeh Jean , Ren Fuquan
Published: June 2022

In this paper, we present a unified grammatical interpretation of the numbers that satisfy a kind of four-term recurrence relation, including the Bell triangle, the coefficients of modified Hermite polynomials, and the Bessel polynomials. Additionally, as an application, a criterion for real zeros of row-generating polynomials is also presented.
BM-Net: CNN-Based MobileNet-V3 and Bilinear Structure for Breast Cancer Detection in Whole Slide Images
Authors: Huang Jin , Mei Liye , Long Mengping , Liu Yiqiang , Sun Wei , Li Xiaoxiao , Shen Hui , Zhou Fuling , Ruan Xiaolan , Wang Du , Wang Shu , Hu Taobo , Lei Cheng
Published: June 2022

Breast cancer is one of the most common types of cancer and is the leading cause of cancer-related death. Diagnosis of breast cancer is based on the evaluation of pathology slides. In the era of digital pathology, these slides can be converted into digital whole slide images (WSIs) for further analysis. However, due to their sheer size, digital WSIs diagnoses are time consuming and challenging. In this study, we present a lightweight architecture that consists of a bilinear structure and MobileNet-V3 network, bilinear MobileNet-V3 (BM-Net), to analyze breast cancer WSIs. We utilized the WSI dataset from the ICIAR2018 Grand Challenge on Breast Cancer Histology Images (BACH) competition, which contains four classes: normal, benign, in situ carcinoma, and invasive carcinoma. We adopted data augmentation techniques to increase diversity and utilized focal loss to remove class imbalance. We achieved high performance, with 0.88 accuracy in patch classification and an average 0.71 score, which surpassed state-of-the-art models. Our BM-Net shows great potential in detecting cancer in WSIs and is a promising clinical tool.
Characteristics of COVID-19 Inpatients in Rehabilitation Units during the First Pandemic Wave: A Cohort Study from a Large Hospital in Champagne Region
Authors: Rapin Amandine , Noujaim Peter-Joe , Taiar Redha , Carazo-Mendez Sandy , Deslee Gaetan , Jolly Damien , Boyer François Constant
Published: June 2022

Background: Data describing patients hospitalized in medical rehabilitation wards after the acute phase of COVID-19 could help to better understand the rehabilitation needs in the current pandemic situation. Methods: Cohort including all patients with COVID-19 hospitalized in a single, large university hospital in Northeast France from 25 February to 30 April 2020. Results: 479 patients were admitted with COVID-19 during the study period, of whom 128 died (26.7%). Among the 351 survivors, 111 were referred to rehabilitation units, including 63 (17.9%) referred to physical and rehabilitation medicine (PRM) units. The median age of patients referred to rehabilitation units was 72 years. Patients who had been in intensive care, or who had had a long hospital stay, required referral to PRM units. Two biomarkers were associated with referral to rehabilitation units, namely, elevated troponin (p = 0.03) and impaired renal function (p = 0.03). Age was associated with referral to PRM units (p = 0.001). Conclusions: Almost one-third of COVID-19 patients required post-acute care, but only one-fifth had access to PRM units. The optimal strategy for post-acute management of COVID-19 patients remains to be determined. The need for rehabilitation wards during a pandemic is a primary concern in enabling the long-term functioning of infected patients.
The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study
Authors: Lund Minna Christiansen , Ellman Ditte Gry , Nissen Maiken , Nielsen Pernille Sveistrup , Nielsen Pernille Vinther , Jørgensen Carina , Andersen Ditte Caroline , Gao Han , Brambilla Roberta , Degn Matilda , Clausen Bettina Hjelm , Lambertsen Kate Lykke
Published: June 2022

Spinal cord injury (SCI) initiates detrimental cellular and molecular events that lead to acute and delayed neuroinflammation. Understanding the role of the inflammatory response in SCI requires insight into the temporal and cellular synthesis of inflammatory mediators. We subjected C57BL/6J mice to SCI and investigated inflammatory reactions. We examined activation, recruitment, and polarization of microglia and infiltrating immune cells, focusing specifically on tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2. In the acute phase, TNF expression increased in glial cells and neuron-like cells, followed by infiltrating immune cells. TNFR1 and TNFR2 levels increased in the delayed phase and were found preferentially on neurons and glial cells, respectively. The acute phase was dominated by the infiltration of granulocytes and macrophages. Microglial/macrophage expression of Arg1 increased from 1–7 days after SCI, followed by an increase in Itgam, Cx3cr1, and P2ry12, which remained elevated throughout the study. By 21 and 28 days after SCI, the lesion core was populated by galectin-3+, CD68+, and CD11b+ microglia/macrophages, surrounded by a glial scar consisting of GFAP+ astrocytes. Findings were verified in postmortem tissue from individuals with SCI. Our findings support the consensus that future neuroprotective immunotherapies should aim to selectively neutralize detrimental immune signaling while sustaining pro-regenerative processes.
Can Introns Stabilize Gene Duplication?
Authors: Micheli Gioacchino , Camilloni Giorgio
Published: June 2022

Gene duplication is considered one of the most important events that determine the evolution of genomes. However, the neo-duplication condition of a given gene is particularly unstable due to recombination events. Several mechanisms have been proposed to justify this step. In this “opinion article” we propose a role for intron sequences in stabilizing gene duplication by limiting and reducing the identity of the gene sequence between the two duplicated copies. A review of the topic and a detailed hypothesis are presented.
Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration
Authors: Galizzi Giacoma , Di Carlo Marta
Published: June 2022

Insulin was discovered and isolated from the beta cells of pancreatic islets of dogs and is associated with the regulation of peripheral glucose homeostasis. Insulin produced in the brain is related to synaptic plasticity and memory. Defective insulin signaling plays a role in brain dysfunction, such as neurodegenerative disease. Growing evidence suggests a link between metabolic disorders, such as diabetes and obesity, and neurodegenerative diseases, especially Alzheimer’s disease (AD). This association is due to a common state of insulin resistance (IR) and mitochondrial dysfunction. This review takes a journey into the past to summarize what was known about the physiological and pathological role of insulin in peripheral tissues and the brain. Then, it will land in the present to analyze the insulin role on mitochondrial health and the effects on insulin resistance and neurodegenerative diseases that are IR-dependent. Specifically, we will focus our attention on the quality control of mitochondria (MQC), such as mitochondrial dynamics, mitochondrial biogenesis, and selective autophagy (mitophagy), in healthy and altered cases. Finally, this review will be projected toward the future by examining the most promising treatments that target the mitochondria to cure neurodegenerative diseases associated with metabolic disorders.
Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4
Authors: Denisov Ilia G. , Grinkova Yelena V. , McLean Mark A. , Camp Tyler , Sligar Stephen G.
Published: June 2022

Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of the possible involvement of new drug candidates in CYP3A4-mediated DDI, we evaluated the application of midazolam (MDZ) as a probe substrate. MDZ is hydroxylated by CYP3A4 in two positions: 1-hydroxy MDZ formed at lower substrate concentrations, and up to 35% of 4-hydroxy MDZ at high concentrations. The ratio of the formation rates of these two products (the site of metabolism ratio, SOM) was used as a measure of allosteric heterotropic interactions caused by effector molecules using CYP3A4 incorporated in lipid nanodiscs. The extent of the changes in the SOM in the presence of effectors is determined by chemical structure and is concentration-dependent. MD simulations of CYP3A4 in the lipid bilayer suggest that experimental results can be explained by the movement of the F-F’ loop and concomitant changes in the shape and volume of the substrate-binding pocket. As a result of PGS binding at the allosteric site, several residues directly contacting MDZ move away from the substrate molecule, enabling the repositioning of the latter for minor product formation.
Cannabidiol and Cannabigerol Inhibit Cholangiocarcinoma Growth In Vitro via Divergent Cell Death Pathways
Authors: Viereckl Michael J. , Krutsinger Kelsey , Apawu Aaron , Gu Jian , Cardona Bryana , Barratt Donovan , Han Yuyan
Published: June 2022

Cholangiocarcinoma (CCA) is a rare and highly lethal disease with few effective treatment options. Cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) are non-psychedelic components extracted from cannabis. These non-psychoactive compounds have shown anti-proliferative potential in other tumor models; however, the efficacy of CBD and CBG in CCA is unknown. Furthermore, two cell death pathways are implicated with CBD resulting in autophagic degeneration and CBG in apoptosis. HuCC-T1 cells, Mz-ChA-1 cells (CCA cell lines) and H69 cells (immortalized cholangiocytes), were treated with CBD and CBG for 24 to 48 h. The influence of these cannabinoids on proliferation was assessed via MTT assay. Apoptosis and cell cycle were evaluated via Annexin-V apoptosis assay and propidium iodide, respectively. The expression of proliferation biomarker Ki-67, apoptosis biomarker BAX, and autophagic flux biomarkers LC3b and LAMP1 were evaluated via immunofluorescence. Cell migration and invasion were evaluated via wound healing assay and trans-well migration invasion assays, respectively. The colony formation was evaluated via colony formation assay. In addition, the expression of autophagy gene LC3b and apoptosis genes BAX, Bcl-2, and cleaved caspase-3 were evaluated via Western blot. CBD and CBG are non-selective anti-proliferative agents yielding similar growth curves in CCA; both cannabinoids are effective, yet CBG is more active at lower doses. Low doses of CBD and CBG enhanced immortalized cholangiocyte activity. The reduction in proliferation begins immediately and occurs maximally within 24 h of treatment. Moreover, a significant increase in the late-stage apoptosis and a reduction in the number of cells in S stage of the cell cycle indicates both CBD and CBG treatment could promote apoptosis and inhibit mitosis in CCA cells. The fluorescent expression of BAX and LC3b was significantly enhanced with CBD treatment when compared to control. LAMP1 and LC3b colocalization could also be observed with CBD and CBG treatment indicating changes in autophagic flux. A significant inhibition of migration, invasion and colony formation ability was shown in both CBD and CBG treatment in CCA. Western blot showed an overall decrease in the ratio of anti-apoptotic protein Bcl-2 with respect to pro-apoptotic protein BAX with CBG treatment. Furthermore, CBD treatment enhanced the expression of Type II cell death (autophagic degeneration) protein LC3b, which was reduced in CBG-treated CCA cells. Meanwhile, CBG treatment upregulated Type I cell death (programmed apoptosis) protein cleaved caspase-3. CBD and CBG are effective anti-cancer agents against CCA, capable of inhibiting the classic hallmarks of cancer, with a divergent mechanism of action (Type II or Type I respectively) in inducing these effects.
Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations
Authors: Murtas Giulia , Pollegioni Loredano , Molla Gianluca , Sacchi Silvia
Published: June 2022

In 2002, the novel human gene G72 was associated with schizophrenia susceptibility. This gene encodes a small protein of 153 amino acids, named pLG72, which represents a rare case of primate-specific protein. In particular, the rs2391191 single nucleotide polymorphism (resulting in in the R30K substitution) was robustly associated to schizophrenia and bipolar disorder. In this review, we aim to summarize the results of 20 years of biochemical investigations on pLG72. The main known role of pLG72 is related to its ability to bind and inactivate the flavoenzyme d-amino acid oxidase, i.e., the enzyme that controls the catabolism of d-serine, the main NMDA receptor coagonist in the brain. pLG72 was proposed to target the cytosolic form of d-amino acid oxidase for degradation, preserving d-serine and protecting the cell from oxidative stress generated by hydrogen peroxide produced by the flavoenzyme reaction. Anyway, pLG72 seems to play additional roles, such as affecting mitochondrial functions. The level of pLG72 in the human body is still a controversial issue because of its low expression and challenging detection. Anyway, the intriguing hypothesis that pLG72 level in blood could represent a suitable marker of Alzheimer’s disease progression (a suggestion not sufficiently established yet) merits further investigations.
Urinary Cystatin C Has Prognostic Value in Peripheral Artery Disease
Authors: Li Ben , Zamzam Abdelrahman , Syed Muzammil H. , Jahanpour Niousha , Jain Shubha , Abdin Rawand , Qadura Mohammad
Published: June 2022

Despite its association with adverse outcomes, peripheral artery disease (PAD) remains undertreated. Cystatin C is elevated in patients with renal disease and may be a marker of cardiovascular disease. We examined the prognostic ability of urinary Cystatin C (uCystatinC) in predicting adverse PAD-related events. In this prospective case-control study, urine samples were collected from patients with PAD (n = 121) and without PAD (n = 77). The cohort was followed for 2 years. uCystatinC was normalized to urinary creatinine (uCr) (uCystatinC/uCr; μg/g). The primary outcome was major adverse limb event (MALE; composite of vascular intervention (open or endovascular) or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI ≥ 0.15). Multivariable Cox regression and Kaplan–Meier analyses were performed to assess the prognostic value of uCystatinC/uCr with regards to predicting MALE and worsening PAD status. Our analysis demonstrated that patients with PAD had significantly higher median [IQR] uCystatinC/uCr levels (24.9 μg/g [14.2–32.9] vs. 20.9 μg/g [11.1–27.8], p = 0.018). Worsening PAD status and MALE were observed in 39 (20%) and 34 (17%) patients, respectively. uCystatinC/uCr predicted worsening PAD status with a hazard ratio (HR) of 1.78 (95% CI 1.12–2.83, p = 0.015), which persisted after controlling for baseline demographic and clinical characteristics (adjusted HR 1.79 [95% CI 1.11–2.87], p = 0.017). Patients with high uCystatinC/uCr had a lower 2-year freedom from MALE (77% vs. 89%, p = 0.025) and worsening PAD status (63% vs. 87%, p = 0.001). Based on these data, higher uCystatinC/uCr levels are associated with adverse PAD-related events and have prognostic value in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management.
Klebsiella pneumoniae Susceptibility to Carbapenem/Relebactam Combinations: Influence of Inoculum Density and Carbapenem-to-Inhibitor Concentration Ratio
Authors: Golikova Maria V. , Alieva Kamilla N. , Filimonova Alla V. , Ageevets Vladimir A. , Sulian Ofeliia S. , Avdeeva Alisa A. , Sidorenko Sergey V. , Zinner Stephen H.
Published: June 2022

The inoculum effect (IE) is a well-known phenomenon with beta-lactams. At the same time, the IE has not been extensively studied with carbapenem/carbapenemase inhibitor combinations. The antibiotic-to-inhibitor concentration ratio used in susceptibility testing can influence the in vitro activity of the combination. To explore the role of these factors, imipenem/relebactam and doripenem/relebactam MICs were estimated against six Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae strains at standard inocula (SI) and high inocula (HI) by two methods: with a fixed relebactam concentration and with a fixed, pharmacokinetic-based carbapenem-to-relebactam concentration ratio. The combination MICs at HI, compared to SI, increased with most of the tested strains. However, the IE occurred with only two K. pneumoniae strains regardless of the MIC testing method. The relationship between the MICs at SI and the respective inoculum-induced MIC changes was observed when the MICs were estimated at pharmacokinetic-based carbapenem-to-relebactam concentration ratios. Thus, (1) IE was observed with both carbapenem/relebactam combinations regardless of the MIC testing method; however, IE was not observed frequently among tested K. pneumoniae strains. (2) At HI, carbapenem/relebactam combination MICs increased to levels associated with carbapenem resistance. (3) Combination MICs determined at pharmacokinetic-based carbapenem-to-inhibitor concentration ratios predict susceptibility elevations at HI in KPC-producing K. pneumoniae.
Mitochondrial Phenotype as a Driver of the Racial Dichotomy in Obesity and Insulin Resistance
Authors: Jevtovic Filip , Krassovskaia Polina M. , Lopez Christian A. , Fisher-Wellman Kelsey H. , Cortright Ronald N. , Broskey Nicholas T.
Published: June 2022

African Americans (AA) are disproportionately burdened by metabolic diseases. While largely unexplored between Caucasian (C) and AA, differences in mitochondrial bioenergetics may provide crucial insight to mechanisms for increased susceptibility to metabolic diseases. AA display lower total energy expenditure and resting metabolic rate compared to C, but paradoxically have a higher amount of skeletal muscle mass, suggestive of inherent energetic efficiency differences between these races. Such adaptations would increase the chances of overnutrition in AA; however, these disparities would not explain the racial difference in insulin resistance (IR) in healthy subjects. Hallmarks associated with insulin resistance (IR), such as reduced mitochondrial oxidative capacity and metabolic inflexibility are present even in healthy AA without a metabolic disease. These adaptations might be influential of mitochondrial “substrate preference” and could play a role in disproportionate IR rates among races. A higher glycolytic flux and provision of shuttles transferring electrons from cytosol to mitochondrial matrix could be a contributing factor in development of IR via heightened reactive oxygen species (ROS) production. This review highlights the above concepts and provides suggestions for future studies that could help delineate molecular premises behind potential impairments in insulin signaling and metabolic disease susceptibility in AA.
Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management
Authors: Rahman Md. Ataur , Ahmed Kazi Rejvee , Rahman MD. Hasanur , Parvez Md. Anowar Khasru , Lee In-Seon , Kim Bonglee
Published: June 2022

Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.
Thrombin Activity in Rodent and Human Skin: Modified by Inflammation and Correlates with Innervation
Authors: Golderman Valery , Berkowitz Shani , Guly Gofrit Shani , Gera Orna , Aharoni Shay Anat , Zohar Daniela Noa , Keren Daria , Dori Amir , Chapman Joab , Shavit-Stein Efrat
Published: June 2022

Thrombin is present in peripheral nerves and is involved in the pathogenesis of neuropathy. We evaluated thrombin activity in skin punch biopsies taken from the paws of male mice and rats and from the legs of patients with suspected small-fiber neuropathy (SFN). In mice, inflammation was induced focally by subcutaneous adjuvant injection to one paw and systemically by intraperitoneal lipopolysaccharides (LPS) administration. One day following injection, thrombin activity increased in the skin of the injected compared with the contralateral and non-injected control paws (p = 0.0009). One week following injection, thrombin increased in both injected and contralateral paws compared with the controls (p = 0.026), coupled with increased heat-sensitivity (p = 0.009). Thrombin activity in the footpad skin was significantly increased one week after systemic administration of LPS compared with the controls (p = 0.023). This was not accompanied by increased heat sensitivity. In human skin, a correlation was found between nerve fiber density and thrombin activity. In addition, a lower thrombin activity was measured in patients with evidence of systemic inflammation compared with the controls (p = 0.0035). These results support the modification of skin thrombin activity by regional and systemic inflammation as well as a correlation with nerve fiber density. Skin thrombin activity measurments may aid in the diagnosis and treatment of SFN.
Biomimetic Self-Adhesive Structures for Wearable Sensors
Authors: Chen Feihu , Han Liuyang , Dong Ying , Wang Xiaohao
Published: June 2022

Inspired by the adhesion ability of various organisms in nature, the research of biomimetic adhesion has shown a promising application prospect in fields such as manipulators, climbing robots and wearable medical devices. In order to achieve effective adhesion between human skin and a variety of wearable sensors, two natural creatures, octopus and mussel, were selected for bio-imitation in this paper. Through imitating the octopus sucker structure, a micro-cavity array with a large inner cavity and small outer cavity was designed. The fabrication was completed by double-layer adhesive photolithography and PDMS molding, and the adhesion capacity of the structure was further enhanced by the coating of thermal responsive hydrogel PNIPAM. The adhesive force of 3.91 N/cm2 was obtained in the range of the human body temperature. PDA-Lap-PAM hydrogel was prepared by combining mussel foot protein (Mfps) with nano-clay (Lap) as biomimetic mussel mucus. It was found that 0.02 g PDA-Lap-PAM hydrogel can obtain about 2.216 N adhesion, with good hydrophilicity. Through oxygen plasma surface treatment and functional silane surface modification, the fusion of the PDMS film with biomimetic octopus sucker structure and the biomimetic mussel mucus hydrogel patch was realized. The biomimetic octopus sucker structure was attached to the human skin surface to solve the problem of shape-preserving attachment, and the biomimetic mussel mucus hydrogel was attached to the sensor surface to solve the problem of sensor surface adaptation. The fusion structure was used to attach a rigid substrate piezoelectric sensor to the skin for a human pulsewave test. The results verified the self-adhesion feasibility of wearable sensors with biomimetic structures.
Source Localization of Audiovisual Multisensory Neural Generators in Young Adults with Attention-Deficit/Hyperactivity Disorder
Authors: McCracken Heather S. , Murphy Bernadette A. , Ambalavanar Ushani , Glazebrook Cheryl M. , Yielder Paul C.
Published: June 2022

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that exhibits unique neurological and behavioural characteristics. Our previous work using event-related potentials demonstrated that adults with ADHD process audiovisual multisensory stimuli somewhat differently than neurotypical controls. This study utilised an audiovisual multisensory two-alternative forced-choice discrimination task. Continuous whole-head electroencephalography (EEG) was recorded. Source localization (sLORETA) software was utilised to determine differences in the contribution made by sources of neural generators pertinent to audiovisual multisensory processing in those with ADHD versus neurotypical controls. Source localization techniques elucidated that the controls had greater neural activity 164 ms post-stimulus onset when compared to the ADHD group, but only when responding to audiovisual stimuli. The source of the increased activity was found to be Brodmann Area 2, postcentral gyrus, right-hemispheric parietal lobe referenced to Montreal Neurological Institute (MNI) coordinates of X = 35, Y = −40, and Z = 70 (p < 0.05). No group differences were present during either of the unisensory conditions. Differences in the integration areas, particularly in the right-hemispheric parietal brain regions, were found in those with ADHD. These alterations may correspond to impaired attentional capabilities when presented with multiple simultaneous sensory inputs, as is the case during a multisensory condition.
Postdiction in Visual Awareness in Schizophrenia
Authors: Kéri Szabolcs
Published: June 2022

Background: The mistiming of predictive thought and real perception leads to postdiction in awareness. Individuals with high delusive thinking confuse prediction and perception, which results in impaired reality testing. The present observational study investigated how antipsychotic medications and cognitive-behavioral therapy (CBT) modulate postdiction in schizophrenia. We hypothesized that treatment reduces postdiction, especially when antipsychotics and CBT are combined. Methods: We enrolled patients with schizophrenia treated in a natural clinical setting and not in a randomized controlled trial. We followed up two schizophrenia groups matched for age, sex, education, and illness duration: patients on antipsychotics (n = 25) or antipsychotics plus CBT (n = 25). The treating clinician assigned the patients to the two groups. Participants completed a postdiction and a temporal discrimination task at weeks 0 and 12. Results: At week 0, postdiction was enhanced in patients relative to controls at a short prediction–perception time interval, which correlated with PANSS positive symptoms and delusional conviction. At week 12, postdiction was reduced in schizophrenia, especially when they received antipsychotics plus CBT. Patients with schizophrenia were also impaired on the temporal discrimination task, which did not change during the treatment. During the 12-week observational period, all PANSS scores were significantly reduced in both clinical groups, but the positive symptoms and emotional distress exhibited a more pronounced response in the antipsychotics plus CBT group. Conclusion: Perceptual postdiction is a putative neurocognitive marker of delusive thinking. Combined treatment with antipsychotics and CBT significantly ameliorates abnormally elevated postdiction in schizophrenia.
Concomitant Impediments to the Social Acceptance of Sandbag Technology for Sustainable and Affordable Housing Delivery: The Case of South Africa
Authors: Adetooto Johnson , Windapo Abimbola
Published: June 2022

There is a high level of homelessness in South Africa. Sandbag building technologies (SBTs) have been offered as economical and sustainable alternative building materials capable of speeding housing provision in South Africa. However, their degree of adoption in South Africa remains relatively low. Furthermore, limited research has examined the low adoption and social acceptance of SBTs, requiring thorough research. Therefore, this research investigates the key social barriers to accepting SBTs in housing provision. The study adopted a mixed method research approach that employs a comprehensive literature review in identifying 18 social barriers to using SBTs and a questionnaire survey of 228 building experts based in South Africa to obtain empirical data. The study findings indicated that the significant impediments were related to the lack of understanding of the benefits of sandbags, a lack of sandbag courses and training, and a lack of professional knowledge and skills, among others. A comparative analysis of the perceptions of the diverse categories of survey participants was conducted and discussed. This study’s evaluation of significant barriers offers government agencies and construction partners a framework to make realistic and well-informed decisions toward more sustainable and affordable housing delivery.
Relationship between Project Space Types, Optimize Energy Performance Credit, and Project Size in LEED-NC Version 4 (v4) Projects: A Case Study
Authors: Pushkar Svetlana
Published: June 2022

A previous study (Pushkar 2021) showed a significant non-parametric correlation between the Optimize Energy Performance credit from the energy and atmosphere category (EAc7) and project size in Leadership in Energy and Environmental Design for New Construction and Major Renovations version 4 (LEED-NC v4) office space projects. However, in such an empirical analysis, there are at least two problems: the choice between parametric and non-parametric statistics, and the choice between the Wilcoxon–Mann–Whitney (WMW) and analysis of covariance (ANCOVA) non-parametric tests. This study aims to evaluate EAc7 credit achievement for different types of spaces in LEED-NC v4 projects. We show that, in order to evaluate the differences between two LEED data groups, (1) a non-parametric procedure is preferable to a parametric one, and (2) if there is Spearman’s correlation between EAc7 credit achievement and project size for the same LEED-NC v4 project, then Quade’s ANCOVA is preferable to WMW. The results of these tests show that, in two out of three cases, office space projects had better EAc7 credit achievement than higher-education spaces at the gold certification level and public assembly spaces at the silver certification level.
Heterogeneity in Melanoma
Authors: Ng Mei Fong , Simmons Jacinta L. , Boyle Glen M.
Published: June 2022

There is growing evidence that tumour heterogeneity has an imperative role in cancer development, evolution and resistance to therapy. Continuing advancements in biomedical research enable tumour heterogeneity to be observed and studied more critically. As one of the most heterogeneous human cancers, melanoma displays a high level of biological complexity during disease progression. However, much is still unknown regarding melanoma tumour heterogeneity, as well as the role it plays in disease progression and treatment response. This review aims to provide a concise summary of the importance of tumour heterogeneity in melanoma.
Can 18F-FDG PET/CT Radiomics Features Predict Clinical Outcomes in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma?
Authors: Jayaprakasam Vetri Sudar , Gibbs Peter , Gangai Natalie , Bajwa Raazi , Sosa Ramon E. , Yeh Randy , Greally Megan , Ku Geoffrey Y. , Gollub Marc J. , Paroder Viktoriya
Published: June 2022

This study aimed to assess the usefulness of radiomics features of 18F-FDG PET/CT in patients with locally advanced esophageal cancers (ESCC) in predicting outcomes such as clinical tumor (cT) and nodal (cN) categories, PET response to induction chemotherapy (PET response), progression-free survival (PFS), and overall survival (OS). Pretreatment PET/CT images from patients who underwent concurrent chemoradiotherapy from July 2002 to February 2017 were segmented, and data were split into training and test sets. Model development was performed on the training datasets and a maximum of five features were selected. Final diagnostic accuracies were determined using the test dataset. A total of 86 PET/CTs (58 men and 28 women, mean age 65 years) were segmented. Due to small lesion size, 12 patients were excluded. The diagnostic accuracies as derived from the CT, PET, and combined PET/CT test datasets were as follows: cT category—70.4%, 70.4%, and 81.5%, respectively; cN category—69.0%, 86.2%, and 86.2%, respectively; PET response—60.0%, 66.7%, and 70.0%, respectively; PFS—60.7%, 75.0%, and 75.0%, respectively; and OS—51.7%, 55.2%, and 62.1%, respectively. A radiomics assessment of locally advanced ESCC has the potential to predict various clinical outcomes. External validation of these models would be further helpful.
P-Cadherin Is Expressed by Epithelial Progenitor Cells and Melanocytes in the Human Corneal Limbus
Authors: Polisetti Naresh , Sharaf Lyne , Martin Gottfried , Schlunck Günther , Reinhard Thomas
Published: June 2022

Interactions between limbal epithelial progenitor cells (LEPC) and surrounding niche cells, which include limbal mesenchymal stromal cells (LMSC) and melanocytes (LM), are essential for the maintenance of the limbal stem cell niche required for a transparent corneal surface. P-cadherin (P-cad) is a critical stem cell niche adhesion molecule at various epithelial stem cell niches; however, conflicting observations were reported on the presence of P-cad in the limbal region. To explore this issue, we assessed the location and phenotype of P-cad+ cells by confocal microscopy of human corneoscleral tissue. In subsequent fluorescence-activated cell sorting (FACS) experiments, we used antibodies against P-cad along with CD90 and CD117 for the enrichment of LEPC, LMSC and LM, respectively. The sorted cells were characterized by immunophenotyping and the repopulation of decellularized limbal scaffolds was evaluated. Our findings demonstrate that P-cad is expressed by epithelial progenitor cells as well as melanocytes in the human limbal epithelial stem cell niche. The modified flow sorting addressing P-cad as well as CD90 and CD117 yielded enriched LEPC (CD90−CD117−P-cad+) and pure populations of LMSC (CD90+CD117−P-cad−) and LM (CD90−CD117+P-cad+). The enriched LEPC showed the expression of epithelial progenitor markers and better colony-forming ability than their P-cad− counterparts. The cultured LEPC and LM exhibited P-cad expression at intercellular junctions and successfully repopulated decellularized limbal scaffolds. These data suggest that P-cad is a critical cell–cell adhesion molecule, connecting LEPC and LM, which may play an important role in the long-term maintenance of LEPC at the limbal stem cell niche; moreover, these findings led to further improvement of cell enrichment protocols to enhance the yield of LEPC.
Age-Related Lysosomal Dysfunctions
Authors: Guerrero-Navarro Lena , Jansen-Dürr Pidder , Cavinato Maria
Published: June 2022

Organismal aging is normally accompanied by an increase in the number of senescent cells, growth-arrested metabolic active cells that affect normal tissue function. These cells present a series of characteristics that have been studied over the last few decades. The damage in cellular organelles disbalances the cellular homeostatic processes, altering the behavior of these cells. Lysosomal dysfunction is emerging as an important factor that could regulate the production of inflammatory molecules, metabolic cellular state, or mitochondrial function.
Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity
Authors: Niedźwiedzka-Rystwej Paulina , Majchrzak Adam , Aksak-Wąs Bogusz , Serwin Karol , Czajkowski Zenon , Grywalska Ewelina , Korona-Głowniak Izabela , Roliński Jacek , Parczewski Miłosz
Published: June 2022

Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.
Relationship Aspects of Mothers and Their Adolescents with Intellectual Disability as Expressed through the Joint Painting Procedure
Authors: Gavron Tami , Feniger-Schaal Rinat , Peretz Adi
Published: June 2022

The quality of the interaction between mothers and their children with an Intellectual Disability (ID) plays a crucial role in their development and in particular during adolescence. This qualitative study was designed to provide a better understanding of aspects of the relationships between mothers and their adolescents with ID through an art-based tool, the Joint Painting Procedure. The qualitative analysis of six dyads of mothers and adolescents with severe, moderate and mild ID was based on the principles of narrative and phenomenological inquiry. The findings yielded three key themes that emerged from the relational dynamics during the JPP: (1) from dependency to autonomy, (2) the joint painting as a way to foster verbal communication, and (3) playfulness and enjoyment. The JPP appeared to serve as a meaningful art-based assessment of the implicit and explicit aspects of the relationships which evolved during the interaction. The findings underscore the potential of the JPP as a non-verbal, art-based tool that allows researchers and clinicians to learn more about the dynamics of relationships between mothers and their adolescents with ID. It also enables a context where the expression of relational issues can be communicated and even transformed.
Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells
Authors: Zhang Zhewen , Yi Juan , Xie Bei , Chen Jing , Zhang Xueyan , Wang Li , Wang Jingyu , Hou Jinxia , Wei Hulai
Published: June 2022

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant (Parkin C431S) HeLa cell models to ascertain whether Parkin-mediated mitophagy participates in ATO-induced apoptosis/cell death. Our data showed that the overexpression of Parkin significantly sensitized HeLa cells to ATO-initiated proliferation inhibition and apoptosis; however, the mutation of Parkin C431S significantly weakened this Parkin-mediated responsiveness. Our further investigation found that ATO significantly downregulated two fusion proteins (Mfn1/2) and upregulated fission-related protein (Drp1). Autophagy was also activated as evidenced by the formation of autophagic vacuoles and mitophagosomes, increased expression of PINK1, and recruitment of Parkin to impaired mitochondria followed by their degradation, accompanied by the increased transformation of LC3-I to LC3-II, increased expression of Beclin1 and decreased expression of P62 in YFP-Parkin HeLa cells. Enhanced mitochondrial fragmentation and autophagy indicated that mitophagy was activated. Furthermore, during the process of mitophagy, the overproduction of ROS implied that ROS might represent a key factor that initiates mitophagy following Parkin recruitment to mitochondria. In conclusion, our findings indicate that Parkin is critically involved in ATO-triggered mitophagy and functions as a potential antiproliferative target in cancer cells.