bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of an Antibiotic Loaded Ceramic-Based Bone Graft Substitute for the Treatment of Infected Non-Unions
Authors: Freischmidt Holger , Armbruster Jonas , Rothhaas Catharina , Titze Nadine , Guehring Thorsten , Nurjadi Dennis , Kretzer Jan Philippe , Schmidmaier Gerhard , Grützner Paul Alfred , Helbig Lars
Published: October 2022

The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, and anti-infective effect of HACaS+G has already been demonstrated in clinical studies on patients with chronic osteomyelitis. However, especially for the treatment of infected non-unions with segmental bone defects by HACaS+G, reliable clinical testing is difficult and sufficient experimental data are lacking. We used an already established sequential animal model in infected and non-infected rat femora to investigate the osteoinductive, osteoconductive, and anti-infective efficacy of HACaS+G for the treatment of infected non-unions. In biomechanical testing, bone consolidation could not be observed under infected and non-infected conditions. Only a prophylactic effect against infections, but no eradication, could be verified in the microbiological analysis. Using µ-CT scans and histology, osteoinduction was detected in both the infected and non-infected bone, whereas osteoconduction occurred only in the non-infected setting. Our data showed that HACaS+G is osteoinductive, but does not have added benefits in infected non-unions in terms of osteoconduction and mechanical bone stability, especially in those with segmental bone defects.
Therapeutic Antiaging Strategies
Authors: Mishra Shailendra Kumar , Balendra Vyshnavy , Esposto Josephine , Obaid Ahmad A. , Maccioni Ricardo B. , Jha Niraj Kumar , Perry George , Moustafa Mahmoud , Al-Shehri Mohammed , Singh Mahendra P. , Khan Anmar Anwar , Vamanu Emanuel , Singh Sandeep Kumar
Published: October 2022

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.
Simple Microcontact Printing Technique to Obtain Cell Patterns by Lithography Using Grayscale, Photopolymer Flexographic Mold, and PDMS
Authors: Gimenez Rocio , Pérez-Sosa Camilo , Bourguignon Natalia , Miriuka Santiago , Bhansali Shekhar , Arroyo Carlos R. , Debut Alexis , Lerner Betiana , Pérez Maximiliano S.
Published: October 2022

Microcontact printing using PDMS embossing tools and its variations have aroused the interest of a wide spectrum of research fields, hence the feasibility of defining micro and nanoscale patterns. In this work, we have proposed and demonstrated a novel lithography method based on grayscale patterns printed in a flexographic photopolymer mold and transferred to epoxy resin and a single PDMS stamp to obtain different microprint pattern structures. The geometry of the patterns can be modified by adjusting the layout and grayscale of the stamp patterns. The functionality of this contact printing methodology was validated by generating human induced pluripotent stem cells (hiPSC) patterns. These specific micropatterns can be very useful for achieving complex differentiation in cell lines such as hiPSC. Microfabrication through the new technique provides a promising alternative to conventional lithography for constructing complex aligned surfaces; these structures could be used as components of biological patterns or microfluidic devices.
Virtual Quartz Crystal Microbalance: Bioinspired Resonant Frequency Tracking
Authors: Burda Ioan
Published: October 2022

The reference acoustic properties of the quartz crystal used as a resonator are ensured by its high-quality factor (Q-factor). The microbalance of the quartz crystal (QCM) exploits the bulk acoustic properties of the quartz crystal. Turning a network analyzer or impedance analyzer into a QCM with a decent measurement rate is a challenge. The use of a virtual instrument to implement an impedance analyzer (VIA) provides greater flexibility to the virtual QCM. In this paper, VIA’s flexibility is exploited for the experimental evaluation of conventional scanning procedures and the influence of associated parameters, in order to identify elements that can lead to a limitation of the performance of a virtual QCM. The results of the experimental investigation justify the use of an innovative and optimized bioinspired scanning procedure to effectively track the serial resonance frequency of the QCM sensor. Variable-resolution spatial sampling of the human retina and the ability of the eye to refocus on the area of interest is the source of bioinspiration for achieving an adaptive virtual QCM. The design methodology and physics are described in detail, and the experimental investigations demonstrate the effectiveness of the proposed bioinspired scanning procedure.
Combined Traction Force–Atomic Force Microscopy Measurements of Neuronal Cells
Authors: Kumarasinghe Udathari , Fox Lucian N. , Staii Cristian
Published: October 2022

In the course of the development of the nervous system, neuronal cells extend (grow) axons, which navigate over distances of the order of many cell diameters to reach target dendrites from other neurons and establish neuronal circuits. Some of the central challenges in biophysics today are to develop a quantitative model of axonal growth, which includes the interactions between the neurons and their growth environment, and to describe the complex architecture of neuronal networks in terms of a small number of physical variables. To address these challenges, researchers need new experimental techniques for measuring biomechanical interactions with very high force and spatiotemporal resolutions. Here we report a unique experimental approach that integrates three different high-resolution techniques on the same platform—traction force microscopy (TFM), atomic force microscopy (AFM) and fluorescence microscopy (FM)—to measure biomechanical properties of cortical neurons. To our knowledge, this is the first literature report of combined TFM/AFM/FM measurements performed for any type of cell. Using this combination of powerful experimental techniques, we perform high-resolution measurements of the elastic modulus for cortical neurons and relate these values with traction forces exerted by the cells on the growth substrate (poly acrylamide hydrogels, or PAA, coated with poly D-lysine). We obtain values for the traction stresses exerted by the cortical neurons in the range 30–70 Pa, and traction forces in the range 5–11 nN. Our results demonstrate that neuronal cells stiffen when axons exert forces on the PAA substrate, and that neuronal growth is governed by a contact guidance mechanism, in which axons are guided by external mechanical cues. This work provides new insights for bioengineering novel biomimetic platforms that closely model neuronal growth in vivo, and it has significant impact for creating neuroprosthetic interfaces and devices for neuronal growth and regeneration.
Sensitivity Enhancement of Hybrid Two-Dimensional Nanomaterials-Based Surface Plasmon Resonance Biosensor
Authors: Zakirov Nurzad , Zhu Shaodi , Bruyant Aurélien , Lérondel Gilles , Bachelot Renaud , Zeng Shuwen
Published: October 2022

In this work, we designed structures based on copper nanosubstrate with graphene and two-dimensional transition metal dichalcogenides (TMDC) in order to achieve an ultrasensitive surface plasmon resonance biosensor. This system contains seven components: SF11 triangular prism, BK-7 glass, Chromium (Cr) adhesion layer, thin copper film, layers of one of the types of transition metal dichalcogenides: MoS2, MoSe2, WS2 or WSe2 (defined as MX2), graphene, sensing layer with biomolecular analyte. Copper was chosen as a plasmonic material because it has a higher conductivity than gold which is commonly used in plasmonic sensors. Moreover, copper is a cheap and widespread material that is easy to produce on a large scale. We have carried out both theoretical and numerical sensitivity calculations of these kinds of structures using the Goos–Hänchen (GH) shift method. GH shift is lateral position displacement of the p-polarized reflected beam from a boundary of two media having different indices of refraction under total internal reflection condition and its value can be retrieved from the phase change of the beam. The SPR signal based on the GH shift is much more sensitive compared to other methods, including angular and wavelength scanning, due to much more abrupt phase change of the SPR reflected light than its intensity ones. By optimizing the parameters of the SPR sensing substrate, such as thickness of copper, number of layers of 2D materials and excitation wavelength, we theoretically showed an enhanced sensitivity with a detection limit 10−9 refractive index unit (RIU).
Emotion Recognition: Photoplethysmography and Electrocardiography in Comparison
Authors: Rinella Sergio , Massimino Simona , Fallica Piero Giorgio , Giacobbe Alberto , Donato Nicola , Coco Marinella , Neri Giovanni , Parenti Rosalba , Perciavalle Vincenzo , Conoci Sabrina
Published: October 2022

Automatically recognizing negative emotions, such as anger or stress, and also positive ones, such as euphoria, can contribute to improving well-being. In real-life, emotion recognition is a difficult task since many of the technologies used for this purpose in both laboratory and clinic environments, such as electroencephalography (EEG) and electrocardiography (ECG), cannot realistically be used. Photoplethysmography (PPG) is a non-invasive technology that can be easily integrated into wearable sensors. This paper focuses on the comparison between PPG and ECG concerning their efficacy in detecting the psychophysical and affective states of the subjects. It has been confirmed that the levels of accuracy in the recognition of affective variables obtained by PPG technology are comparable to those achievable with the more traditional ECG technology. Moreover, the affective psychological condition of the participants (anxiety and mood levels) may influence the psychophysiological responses recorded during the experimental tests.
Investigation of Spatiotemporal Profiles of Single-Pulse TMS-Evoked Potentials with Active Stimulation Compared with a Novel Sham Condition
Authors: Takano Mayuko , Wada Masataka , Zomorrodi Reza , Taniguchi Keita , Li Xuemei , Honda Shiori , Tobari Yui , Mimura Yu , Nakajima Shinichiro , Kitahata Ryosuke , Mimura Masaru , Daskalakis Zafiris J. , Blumberger Daniel M. , Noda Yoshihiro
Published: October 2022

Identifying genuine cortical stimulation-elicited electroencephalography (EEG) is crucial for improving the validity and reliability of neurophysiology using transcranial magnetic stimulation (TMS) combined with EEG. In this study, we evaluated the spatiotemporal profiles of single-pulse TMS-elicited EEG response administered to the left dorsal prefrontal cortex (DLPFC) in 28 healthy participants, employing active and sham stimulation conditions. We hypothesized that the early component of TEP would be activated in active stimulation compared with sham stimulation. We specifically analyzed the (1) stimulus response, (2) frequency modulation, and (3) phase synchronization of TMS–EEG data at the sensor level and the source level. Compared with the sham condition, the active condition induced a significant increase in TMS-elicited EEG power in the 30–60 ms time interval in the stimulation area at the sensor level. Furthermore, in the source-based analysis, the active condition induced significant increases in TMS-elicited response in the 30–60 ms compared with the sham condition. Collectively, we found that the active condition could specifically activate the early component of TEP compared with the sham condition. Thus, the TMS–EEG method that was applied to the DLPFC could detect the genuine neurophysiological cortical responses by properly handling potential confounding factors such as indirect response noises.
Polydopamine-Functionalized Copper Peroxide/ZIF-8 Nanoparticle-Based Fluorescence-Linked Immunosorbent Assay for the Sensitive Determination of Carcinoembryonic Antigen by Self-Supplied H2O2 Generation
Authors: Huang Juanjuan , Yao Yiyun , Chen Yanling , Lin Tianran , Hou Li , Tang Dianping
Published: October 2022

Copper peroxide/zeolitic imidazolate framework/polydopamine nanoparticles (CP/ZIF-8/PDA)-based fluorescence-linked immunosorbent assay (FLISA) was designed for the sensitive and high-throughput determination of carcinoembryonic antigen (CEA) by self-supplied H2O2 generation. Specifically, the CEA aptamer was modified on the surface of CP/ZIF-8/PDA to form an immunoprobe. The structures of CP and ZIF-8 could be broken under acidic conditions, and produced the Cu2+ and H2O2 due to the dissociation the CP. A subsequent Fenton-type reaction of Cu2+ and H2O2 generated hydroxyl radical (·OH). o-phenylenediamine (OPD) was oxidized by the ·OH to form 2, 3-diaminophenazine (DPA) with a significant fluorescence signal. CP/ZIF-8/PDA could be used as an efficient Fenton-type reactant to generate a large amount of ·OH to promote OPD oxidation. The sensitive detection of CEA could be realized. Under optimal conditions, the FLISA platform displayed a linear detection range from 0.01 to 20 ng mL−1 with a detection limit of 7.6 pg mL−1 for CEA. This strategy has great application potential for sensitive and high-throughput determination for other biomarkers in the field of biomedicine.
An Optimization Framework for Silicon Photonic Evanescent-Field Biosensors Using Sub-Wavelength Gratings
Authors: Puumala Lauren S. , Grist Samantha M. , Wickremasinghe Kithmin , Al-Qadasi Mohammed A. , Chowdhury Sheri Jahan , Liu Yifei , Mitchell Matthew , Chrostowski Lukas , Shekhar Sudip , Cheung Karen C.
Published: October 2022

Silicon photonic (SiP) evanescent-field biosensors aim to combine the information-rich readouts offered by lab-scale diagnostics, at a significantly lower cost, and with the portability and rapid time to result offered by paper-based assays. While SiP biosensors fabricated with conventional strip waveguides can offer good sensitivity for label-free detection in some applications, there is still opportunity for improvement. Efforts have been made to design higher-sensitivity SiP sensors with alternative waveguide geometries, including sub-wavelength gratings (SWGs). However, SWG-based devices are fragile and prone to damage, limiting their suitability for scalable and portable sensing. Here, we investigate SiP microring resonator sensors designed with SWG waveguides that contain a “fishbone” and highlight the improved robustness offered by this design. We present a framework for optimizing fishbone-style SWG waveguide geometries based on numerical simulations, then experimentally measure the performance of ring resonator sensors fabricated with the optimized waveguides, targeting operation in the O-band and C-band. For the O-band and C-band devices, we report bulk sensitivities up to 349 nm/RIU and 438 nm/RIU, respectively, and intrinsic limits of detection as low as 5.1 × 10−4 RIU and 7.1 × 10−4 RIU, respectively. This performance is comparable to the state of the art in SWG-based sensors, positioning fishbone SWG resonators as an attractive, more robust, alternative to conventional SWG designs.
A Biomass Based Photonic Crystal Hydrogel Made of Bletilla striata Polysaccharide
Authors: Sun Bo , Zhang Wenxin , Liu Yangyang , Xue Min , Qiu Lili , Meng Zihui
Published: October 2022

Bletilla striata is an herb with a good medicinal value whose main active ingredient is Bletilla striata polysaccharide (BSP) in the tuber of Bletilla striata. In this study, a polysaccharide-based semi-interpenetrating network hydrogel was constructed by introducing BSP into polyacrylamide (PAM) hydrogel. The introduction of the BSP chain no only maintains the excellent mechanical properties of PAM, but also endows it with good biocompatibility. By implanting the colloidal crystal array into the above hydrogels, we obtained a novel biomass-based photonic crystal with good stimulus responsiveness that is sensitive to volatile organic compounds (VOCs), especially alcohol vapor. In addition, due to the scavenging ability of BSP to hydroxyl radicals, the photonic crystal hydrogel also has a good response to hydrogen peroxide (H2O2).
Advances in Novel Nanomaterial-Based Optical Fiber Biosensors—A Review
Authors: Li Muyang , Singh Ragini , Wang Yiran , Marques Carlos , Zhang Bingyuan , Kumar Santosh
Published: October 2022

This article presents a concise summary of current advancements in novel nanomaterial-based optical fiber biosensors. The beneficial optical and biological properties of nanomaterials, such as nanoparticle size-dependent signal amplification, plasmon resonance, and charge-transfer capabilities, are widely used in biosensing applications. Due to the biocompatibility and bioreceptor combination, the nanomaterials enhance the sensitivity, limit of detection, specificity, and response time of sensing probes, as well as the signal-to-noise ratio of fiber optic biosensing platforms. This has established a practical method for improving the performance of fiber optic biosensors. With the aforementioned outstanding nanomaterial properties, the development of fiber optic biosensors has been efficiently promoted. This paper reviews the application of numerous novel nanomaterials in the field of optical fiber biosensing and provides a brief explanation of the fiber sensing mechanism.
Rapid Quantitative Detection of Live Escherichia coli Based on Chronoamperometry
Authors: Cao Zhuosong , Li Chenyu , Yang Xiaobo , Wang Shang , Zhang Xi , Zhao Chen , Xue Bin , Gao Chao , Zhou Hongrui , Yang Yutong , Shen Zhiqiang , Sun Feilong , Wang Jingfeng , Qiu Zhigang
Published: October 2022

The rapid quantitative detection of Escherichia coli (E. coli) is of great significance for evaluating water and food safety. At present, the conventional bacteria detection methods cannot meet the requirements of rapid detection in water environments. Herein, we report a method based on chronoamperometry to rapidly and quantitatively detect live E. coli. In this study, the current indicator i0 and the electricity indicator A were used to record the cumulative effect of bacteria on an unmodified glassy carbon electrode (GCE) surface during chronoamperometric detection. Through the analysis of influencing factors and morphological characterization, it was proved that the changes of the two set electrochemical indicator signals had a good correlation with the concentration of E. coli; detection time was less than 5 min, the detection range of E. coli was 104–108 CFU/mL, and the error range was <30%. The results of parallel experiments and spiking experiments showed that this method had good repeatability, stability, and sensitivity. Humic acid and dead cells did not affect the detection results. This study not only developed a rapid quantitative detection method for E. coli in the laboratory, but also realized a bacterial detection scheme based on the theory of bacterial dissolution and adsorption for the first time, providing a new direction and theoretical basis for the development of electrochemical biosensors in the future.
Association between Arousals during Sleep and Subclinical Coronary Atherosclerosis in Patients with Obstructive Sleep Apnea
Authors: Lu Mi , Yu Wei , Wang Zhenjia , Huang Zhigang
Published: October 2022

(1) Aim: We aim to evaluate the association between arousals during sleep and subclinical coronary atherosclerosis detected by coronary computed tomography angiography (CTA) in patients with obstructive sleep apnea (OSA). (2) Methods: This was a cross-sectional study. Consecutive newly diagnosed OSA patients, who underwent coronary CTA examinations within 3 months of the sleep study, were eligible. We used the arousal index (ArI) derived from polysomnography to assess arousals during sleep and a semi-automated plaque quantification software to characterize and quantify the subclinical coronary atherosclerosis. Multiple regression models were used to evaluate the associations of the ArI with the coronary atherosclerotic plaque presence, volume, and composition. (3) Results: A total of 99 patients with OSA were included in the study. In the multivariable models, patients with a high ArI (ArI > 32.2 events/h) were more likely to have coronary plaques compared to those with a low ArI (ArI ≤ 32.2 events/h) (OR: 3.29 [95% CI: 1.284 to 8.427], p = 0.013). Furthermore, the ArI exhibited significant associations with total (β = 0.015), noncalcified (β = 0.015), and low-attenuation (β = 0.012) coronary plaque volume after accounting for established risk factors (p = 0.008, 0.004, and 0.002, respectively). However, no association between the ArI and calcified plaque volume was found. (4) Conclusion: Repetitive arousals during sleep are associated with an increased coronary plaque burden in patients with OSA, which remained robust after adjusting for multiple established cardiovascular risk factors.
White Button Mushroom (Agaricus bisporus) Supplementation Ameliorates Spatial Memory Deficits and Plaque Formation in an Amyloid Precursor Protein Mouse Model of Alzheimer’s Disease
Authors: Dimopoulos Thalia T. , Lippi Stephen L. P. , Davila Jorge Fernandez , Barkey Rachel E. , Doherty Erin N. , Flinn Jane M.
Published: October 2022

Alzheimer’s Disease (AD) is characterized by cognitive impairment and the presence of amyloid-β (Aβ) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aβ). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet. Morris water maze (MWM) was conducted at 14 and 32 weeks of age to assess spatial memory and Aβ plaque pathology in the hippocampus was analyzed. Our results showed that hAPP mice on the WBM diet were faster in reaching the platform in the MWM compared to hAPP mice on the control diet at 32 weeks (p < 0.05). Significantly fewer plaque deposits were found in the hippocampi of hAPP mice on the WBM diet compared to those on the control diet at 32 weeks (p < 0.05). Overall, hAPP mice on the WBM diet had improved spatial memory at 32 weeks of age compared to those on the control diet and exhibited fewer amyloid plaques.
Association between Motor Signs and Cognitive Performance in Cognitively Unimpaired Older Adults: A Cross-Sectional Study Using the NACC Database
Authors: Siokas Vasileios , Liampas Ioannis , Lyketsos Constantine G. , Dardiotis Efthimios
Published: October 2022

Aiming to examine whether specific motor signs are associated with worse performance in specific cognitive domains among cognitively unimpaired (CU) individuals, we performed a cross-sectional analysis of data from the baseline evaluations of older, CU participants from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. In total, 8149 CU (≥60 years) participants were included. Of these, 905 individuals scored ≥ 2 on at least one of the motor domains of the Unified Parkinson’s Disease Rating Scale part III (UPDRSIII). Cognitively impaired individuals, participants with psychiatric disorders and/or under treatment with antipsychotic, anxiolytic, sedative or hypnotic agents were excluded. Nine motor signs were examined: hypophonia, masked facies, resting tremor, action/postural tremor, rigidity, bradykinesia, impaired chair rise, impaired posture/gait and postural instability. Their association with performance on episodic memory, semantic memory, language, attention, processing speed or executive function was assessed using crude and adjusted linear regression models. Individuals with impaired chair rise had worse episodic memory, semantic memory, processing speed and executive function, while those with bradykinesia had worse language, processing speed and executive function. Sensitivity analyses, by excluding participants with cerebrovascular disease or PD, or other Parkinsonism, produced similar results with the exception of the relationship between bradykinesia and language performance.
Deriving Information on Play and Playfulness of 3–5-Year-Olds from Short Written Descriptions: Analyzing the Frequency of Usage of Indicators of Playfulness and Their Associations with Maternal Playfulness
Authors: Tandler Nancy , Proyer René T.
Published: October 2022

Playfulness is an individual differences variable that enables people to (re-)frame almost any situation into an entertaining, amusing, intellectually stimulating and/or personally interesting situation by interacting playfully with others, by resolving tension, by liking complexity over simplicity and/or by having a preference for unusual topics, persons and/or activities. We asked 208 German-speaking mothers of 3–5-year-olds to describe their child in 5–10 sentences. Using a list of criteria for playfulness (e.g., actively initiating humor, playful exchange with others or widespread interests), we found that mothers used, on average, two playful characteristics to describe their child (17% did not report any). Greater usage of playful descriptors in the written texts was positively related mainly to greater other-directed and intellectual playfulness of the mothers. The findings are encouraging and suggest that the list of playful criteria in descriptions of children could be used in the study of inter-individual differences in playfulness in young children.
A Fairer Renewable Energy Policy for Aged Care Communities: Data Driven Insights across Climate Zones
Authors: Liu Aaron , Miller Wendy , Yigitcanlar Tan , Zedan Sherif , Yang Yang , Chiou James , Mantis James , O’Sullivan Michael
Published: October 2022

Communal living for older people exists in many different forms, such as suburban communities, lifestyle communities, retirement villages and residential aged care communities (RAC) where electricity is supplied via a main gate meter to the whole community. Australia’s Small-scale Renewable Energy Scheme incentivizes individuals and businesses to install renewable energy systems up to 100 kW peak. A system of this size, however, may not meet a community’s energy needs or sustainability goals. In contrast, other residential dwellings are allowed to install a minimum solar inverter of 5 kW. Therefore, this paper investigates small-scale renewable energy targets on a per bed basis for RACs and the impact of a change from the current 100 kW peak small-scale renewable energy policy. A data driven clustering-based method has been implemented to identify financially optimal photovoltaic (PV) system ratings for ten RACs across four climate zones. Explored are 100 kW peak PV and net zero electricity scenarios. Results show RACs with 5 kW PV per bed can move closer to a net zero electricity goal and generate 800 to 1400 GWh of renewable electricity each year with significant financial savings. A fairer renewable policy, based on kilowatts per bed, is advocated to improve communities’ energy resilience, financial sustainability, and environmental sustainability.
Applications of Focused Ultrasound for the Treatment of Glioblastoma: A New Frontier
Authors: Hersh Andrew M. , Bhimreddy Meghana , Weber-Levine Carly , Jiang Kelly , Alomari Safwan , Theodore Nicholas , Manbachi Amir , Tyler Betty M.
Published: October 2022

Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood–brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.
Spatial Profiling of the Prostate Cancer Tumor Microenvironment Reveals Multiple Differences in Gene Expression and Correlation with Recurrence Risk
Authors: Kumar Vinay , Randhawa Pavneet , Bilodeau Robert , Mercola Dan , McClelland Michael , Agrawal Anshu , Nguyen James , Castro Patricia , Ittmann Michael M. , Rahmatpanah Farah
Published: October 2022

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.
Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells
Authors: Loubaki Lionel , Rouabhia Mahmoud , Zahrani Mohamed Al , Amri Abdullah Al , Semlali Abdelhabib
Published: October 2022

Cannabinoids, the active components of cannabis exert palliative effects in cancer patients by preventing nausea, vomiting and pain as well as by stimulating appetite. Recent studies indicated that cannabinoids could be helpful in treating certain rare forms of cancer and other inflammatory diseases. The objective of this study was to investigate the cytotoxic effect of a cannabinoid mixture (CM) in oral cells. Thus, normal and cancer gingival cells were treated with different concentrations of CM to evaluate their proliferation by MTT assay, cytotoxicity by using LDH assay, colony formation with crystal violet and migration by the scratch method. In addition, apoptosis, autophagy, oxidative stress, antioxidant level, DNA damage and the mitochondrial membrane potential (ΔΨm) generated by proton pumps were measured by flow cytometry. Furthermore, deactivation of the key signaling pathways involved in cancer progression such as NF-κB, ERK1/2, p38, STAT1, STAT3, STAT5 was also evaluated by this technique. These outcomes indicate that CM, at a concentration higher than 0.1 µg/mL, provokes high cytotoxicity in Ca9-22 oral cancer cells but not in GMSM-K gingival normal cells. Apoptosis, autophagy, antioxidant levels and mitochondrial stress as well as DNA damage in oral cells were increased following exposure to low concentration (1 µg/mL). In addition, major signaling pathways that are involved such as MAPKase, STATs and NF-κB pathways were inhibited by CM as well as cell migration. Our results suggest that cannabinoids could potentially have a beneficial effect on oral cancer therapy.
The Role of MARCKS in Metastasis and Treatment Resistance of Solid Tumors
Authors: Chiu Chun-Lung , Zhao Hongjuan , Chen Ching-Hsien , Wu Reen , Brooks James D.
Published: October 2022

The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells. MARCKS plays important roles in multiple cellular processes, including cell adhesion and motility, mucin secretion, exocytosis, and inflammatory response. Aberrant MARCKS signaling has been observed in the development and progression of multiple cancer types. In addition, MARCKS facilitates cancer metastasis through modulating cancer cell migration and invasion. Moreover, MARCKS contributes to treatment resistance, likely by promoting cancer stem cell renewal as well as immunosuppression. In this review, we describe MARCKS protein structure, cellular localization, and biological functions. We then discuss the role of MARCKS in cancer metastasis as well as its mechanisms of action in solid tumors. Finally, we review recent advances in targeting MARCKS as a new therapeutic strategy in cancer management.
Presumed Roles of APRO Family Proteins in Cancer Invasiveness
Authors: Ikeda Yuka , Taniguchi Kurumi , Sawamura Haruka , Yoshikawa Sayuri , Tsuji Ai , Matsuda Satoru
Published: October 2022

The APRO family members may be involved in the regulation of cell growth, migration, and/or invasion. Although an APRO protein could suppress the invasiveness of several cancer cells, it has been reported that overexpression of the same APRO protein could also promote the invasiveness and/or metastasis of the same cancer cells. In general, the invasiveness of cancer cells might be associated with the function of matrix metalloproteinases (MMPs) as well as with the function of certain exosomes. However, it has been shown that exosomes involving particular APRO proteins, MMPs, and/or microRNA could contribute to the regulation of invasiveness. Here, we discuss contradictory reports on invasiveness in relation to APRO family proteins on the basis of understanding the function of MMPs and/or various exosomes. A better understanding of those mechanisms could be of use to bring about innovative strategies for cancer treatment.
Risk of Presenting with Poor-Prognosis Metastatic Cancer in Adolescents and Young Adults: A Population-Based Study
Authors: Bhutada Jessica K. Sheth , Hwang Amie E. , Liu Lihua , Tsai Kai-Ya , Deapen Dennis , Freyer David R.
Published: October 2022

Having metastatic disease at diagnosis poses the great risk of death among AYAs with cancer from all sociodemographic subgroups. This “landscape” study utilized United States Surveillance, Epidemiology, and End Results Program data from 2000–2016 to identify subgroups of AYAs at highest risk for presenting with metastases across twelve cancer sites having a poor-prognosis (5-year survival <50% with metastases). Adjusted odds ratios for risk of metastatic disease presentation were compared for AYAs in aggregate and by sociodemographic subgroup (race/ethnicity, sex, socioeconomic status [SES]). In general, AYAs who were male, racial/ethnic minorities, or low SES were at consistently greatest risk of metastases. Strikingly, having metastatic melanoma was independently associated with multiple AYA sociodemographic subgroups, including males (aOR 3.11 [95% CI 2.64–3.66]), non-Hispanic Blacks (4.04 [2.32–7.04]), Asian Pacific Islanders (2.99 [1.75–5.12]), Hispanics (2.37 [1.85–3.04]), and low SES (2.30 [1.89–2.80]). Non-Hispanic Blacks were more likely to present with metastatic cancer in all sites, except for bone, rhabdomyosarcoma, and stomach. Low SES AYAs are more likely to present with metastatic melanoma, bone tumors, soft tissue sarcomas, breast, cervical, lung, and stomach carcinomas. Building on these results, future cancer-specific studies should investigate the connection between sociodemographic risk factors and biological drivers of metastases. This line of research has potential to inform targeted public health and screening efforts to facilitate risk reduction and earlier detection of these deadly diseases.
Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer
Authors: Jehanno Charly , Le Goff Pascale , Habauzit Denis , Le Page Yann , Lecomte Sylvain , Lecluze Estelle , Percevault Frédéric , Avner Stéphane , Métivier Raphaël , Michel Denis , Flouriot Gilles
Published: October 2022

Estrogen receptor-alpha (ERα) is the driving transcription factor in 70% of breast cancers and its activity is associated with hormone dependent tumor cell proliferation and survival. Given the recurrence of hormone resistant relapses, understanding the etiological factors fueling resistance is of major clinical interest. Hypoxia, a frequent feature of the solid tumor microenvironment, has been described to promote endocrine resistance by triggering ERα down-regulation in both in vitro and in vivo models. Yet, the consequences of hypoxia on ERα genomic activity remain largely elusive. In the present study, transcriptomic analysis shows that hypoxia regulates a fraction of ERα target genes, underlying an important regulatory overlap between hypoxic and estrogenic signaling. This gene expression reprogramming is associated with a massive reorganization of ERα cistrome, highlighted by a massive loss of ERα binding sites. Profiling of enhancer acetylation revealed a hormone independent enhancer activation at the vicinity of genes harboring hypoxia inducible factor (HIFα) binding sites, the major transcription factors governing hypoxic adaptation. This activation counterbalances the loss of ERα and sustains hormone-independent gene expression. We describe hypoxia in luminal ERα (+) breast cancer as a key factor interfering with endocrine therapies, associated with poor clinical prognosis in breast cancer patients.
Machine Learning-Based Genome-Wide Salivary DNA Methylation Analysis for Identification of Noninvasive Biomarkers in Oral Cancer Diagnosis
Authors: Adeoye John , Wan Chi Ching Joan , Zheng Li-Wu , Thomson Peter , Choi Siu-Wai , Su Yu-Xiong
Published: October 2022

This study aims to examine the feasibility of ML-assisted salivary-liquid-biopsy platforms using genome-wide methylation analysis at the base-pair and regional resolution for delineating oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A nested cohort of patients with OSCC and OPMDs was randomly selected from among patients with oral mucosal diseases. Saliva samples were collected, and DNA extracted from cell pellets was processed for reduced-representation bisulfite sequencing. Reads with a minimum of 10× coverage were used to identify differentially methylated CpG sites (DMCs) and 100 bp regions (DMRs). The performance of eight ML models and three feature-selection methods (ANOVA, MRMR, and LASSO) were then compared to determine the optimal biomarker models based on DMCs and DMRs. A total of 1745 DMCs and 105 DMRs were identified for detecting OSCC. The proportion of hypomethylated and hypermethylated DMCs was similar (51% vs. 49%), while most DMRs were hypermethylated (62.9%). Furthermore, more DMRs than DMCs were annotated to promoter regions (36% vs. 16%) and more DMCs than DMRs were annotated to intergenic regions (50% vs. 36%). Of all the ML models compared, the linear SVM model based on 11 optimal DMRs selected by LASSO had a perfect AUC, recall, specificity, and calibration (1.00) for OSCC detection. Overall, genome-wide DNA methylation techniques can be applied directly to saliva samples for biomarker discovery and ML-based platforms may be useful in stratifying OSCC during disease screening and monitoring.
Hepcidin in Children and Adults with Acute Leukemia or Undergoing Hematopoietic Cell Transplantation: A Systematic Review
Authors: Słomka Artur , Łęcka Monika , Styczyński Jan
Published: October 2022

Objectives: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies. Methods: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines. Results: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient’s age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT. Conclusions: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.
Flow Cytometric Analysis of Bone Marrow Particle Cells for Measuring Minimal Residual Disease in Multiple Myeloma
Authors: Jiang Duanfeng , Zhang Yanan , Tan Shiming , Liu Jing , Li Xin , Zhang Congming
Published: October 2022

Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM). However, the hemodilution of bone marrow (BM) aspirates, the most common preanalytical problem, is known to affect MRD detection. In the present study, we analyzed a preanalytical method for routine BM aspirates and a bone marrow particle cell (BMPL) enrichment assay and validated it as a reliable preanalytical method for flow cytometric MRD determination. A total of 120 BM samples were taken from 103 MM patients consecutively recruited; 77 BM samples had BMPL enrichment analysis and 99 BM samples were routinely analyzed. Then, the two different samples from patients with MM were sent for MRD detection using an eight-color flow cytometry. Our data showed that assessment of the BMPL enrichment samples attenuated the overestimation of MRD-negative assessed in the routine BM samples, which was mainly caused by hemodilution. In conclusion, the BMPL enrichment assay is a functional and practical preanalytical method for flow cytometric MRD analysis.
Nitrogen-Doped Pitch-Based Activated Carbon Fibers with Multi-Dimensional Metal Nanoparticle Distribution for the Effective Removal of NO
Authors: Chang Shengkai , Han Zhuo , Yang Jianxiao , Chen Xuli , Liu Jiahao , Liu Yue , Li Jun
Published: October 2022

The design of catalytic materials for NOX removal by the selective catalytic reduction with NH3 (NH3-SCR) has been a focus of research in the field of waste gas treatment. In this work, pitch-based activated carbon fibers (ACFs) were impregnated with copper nitrate and cerium nitrate, and then the ACFs that were loaded with bimetallic nanoparticles (ACF@Cu/Ce) were obtained after the pyrolyzation and reduction were performed. Moreover, the ACF@Cu/Ce were furtherly treated through the chemical vapor deposition and NH3 activation, through which the N-doped carbon nanofibers (N-CNFs) were grown on the surface of the ACFs. Thus, the catalytic material with a multi-dimensional metal nanoparticle distribution and nitrogen-rich network structure, namely the N-CNF/ACF@Cu/Ce, was constructed. In the NH3-SCR reaction, the NO conversion of the N-CNF/ACF@Cu/Ce could be maintained at about 72~81% in a wide temperature window of 295~495 °C, which enabled the N-CNF/ACF@Cu/Ce to meet the requirements of the practical applications.
Improved the Light Adsorption and Separation of Charge Carriers to Boost Photocatalytic Conversion of CO2 by Using Silver Doped ZnO Photocatalyst
Authors: Hoai Pham Thi Thu , Huong Nguyen Thi Mai , Huong Pham Thi , Viet Nguyen Minh
Published: October 2022

This work developed a strategy to enhance the photocatalytic activity of ZnO by doping it with silver nanoparticles (Ag) to improve the light adsorption and separation of charge carriers, which further increases the conversion of CO2. The loading of Ag over ZnO (Ag-ZnO) was confirmed by characterization methods (SEM, XRD, and XPS), and the photocatalytic activities of Ag-ZnO were significantly enhanced. As the result, the production rates of CO and CH4 by doped Ag-ZnO were 9.8 and 2.4 µmol g−1 h−1, respectively. The ZnO that had the production rate of CO was 3.2 µmol g−1 h−1 and it is relatively low for the production of CH4 at around 0.56 µmol g−1 h−1. The doping of Ag over ZnO displayed a high conversion rate for both CO and CH4, which were 3 and 4.2 times higher than that of ZnO. The doped Ag-ZnO photocatalyst also had high stability up to 10 cycles with less than 11% loss in the production of CO and CH4. The improvement of photocatalytic activities of Ag-ZnO was due to the Ag doping, which enhanced the light adsorption (400–500 nm) and narrowed band gap energy (2.5 eV), preventing the charge carrier separation. This work brings an efficient photocatalyst for CO2 conversion in order to reduce carbon dioxide concentration as well as greenhouse gas emissions.