bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Familial Hypercholesterolemia with Special Emphasis on Evinacumab
Authors: Krzemińska Julia , Młynarska Ewelina , Radzioch Ewa , Wronka Magdalena , Rysz Jacek , Franczyk Beata
Published: December 2022

Familial hypercholesterolemia (FH) is an underdiagnosed disease that contributes to a significant number of cardiovascular incidents through high serum Low-Density Lipoprotein Cholesterol (LDL-C) values. Its treatment primarily requires healthy lifestyle and therapy based on statins, ezetimibe and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); however, there are also new treatment options that can be used in patients who do not respond to therapy, among which we highlight evinacumab. Elevated LDL-C values, together with clinical manifestations associated with cholesterol deposition (e.g., tendon xanthomas, xanthelasma and arcus cornealis) and family history are the main elements in the diagnosis of FH. Pathognomonic signs of FH include extensor tendon xanthomas; however, their absence does not exclude the diagnosis. Elevated LDL-C levels lead to premature Atherosclerotic Cardiovascular Disease (ASCVD), which is why early diagnosis and treatment of FH is essential. Evinacumab, a novelty in pharmacological practice, having a complex mechanism of action, causes desirable changes in lipid parameters in patients with homozygous form of familial hypercholesterolemia (HoFH). This review collects and summarizes the most important aspects of the new drug, especially being a discovery in the treatment of HoFH, giving these patients hope for a longer and more comfortable life.
Development and Characterization of Phage-Display-Derived Novel Human Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2
Authors: Kim Ji Woong , Min Sung Won , Lee Jichul , Shin Ha Gyeong , Choi Hye Lim , Yang Ha Rim , Lee Ji Hyun , Cho Yea Bin , Shim Hyunbo , Lee Sukmook
Published: December 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic crisis, caused by the life-threatening illness coronavirus disease 2019 (COVID-19). Thus, the rapid development of monoclonal antibodies (mAbs) to cope with COVID-19 is urgently necessary. In this study, we used phage display to develop four human mAbs specific to the receptor-binding domain (RBD) of SARS-CoV-2. Our intensive in vitro functional analyses demonstrated that K102.1, an anti-SARS-CoV-2 RBD-specific mAb, exerted potent neutralizing activity against pseudoviral and live viral infection and the interaction between SARS-CoV-2 RBD and human angiotensin-converting enzyme 2. Monotherapy with K102.1 also revealed the therapeutic potential against SARS-CoV-2 infection in vivo. Further, this study developed a sandwich enzyme-linked immunosorbent assay with a non-competing mAb pair, K102.1 and K102.2, that accurately detected the RBDs of SARS-CoV-2 wild-type and variants with high sensitivity in the picomolar range. These findings suggest that the phage-display-based mAb selection from an established antibody library may be an effective strategy for the rapid development of mAbs against the constantly evolving SARS-CoV-2.
Oxaliplatin-Related Hypersensitivity Reactions: A Single Institution Series and Literature Review
Authors: Barbin Francesca , Ghidini Michele , Panichi Alessandra , Tomasello Gianluca , Bareggi Claudia , Galassi Barbara , Denaro Nerina , Ruatta Fiorella , Cauchi Carolina , Rossino Maria Grazia , Garrone Ornella
Published: December 2022

Oxaliplatin-based chemotherapy is extensively used for the treatment of gastrointestinal tumors and other malignancies. Oxaliplatin-related hypersensitivity reactions (HSRs) are common during antitumor treatment. Several studies have been conducted to identify predictive risk factors for oxaliplatin-related HSRs, but findings remain controversial. No definitive approach has been identified to reduce the risk of developing HSRs. The aim of this article is to provide an overview of oxaliplatin-related HSRs, and to report our institution’s experience. With our work, we reviewed available data from the literature and described our case series. A total of 153 patients were treated with oxaliplatin and 17 developed an HSR. On the whole, 70.6% of reactions were Grade 3, mostly with respiratory and cutaneous symptoms. Steroids and antihistamines were administered to reduce hypersensitivity symptoms and prevent further reactions. A stronger premedication and prolonged time of infusion resulted in milder reactions or absence of subsequent reactions. We did not find any clear predictive factor for the development of HSRs. Although it is not possible to cancel the risk of oxaliplatin-based HSRs, strategies to reduce the risk of occurrence could be stronger premedication and prolonged time of infusion.
Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective
Authors: Cavallaro Dalila , Guerrieri Marco , Cattelan Stefano , Fabbri Gaia , Croce Sara , Armati Martina , Bennett David , Fossi Antonella , Voltolini Luca , Luzzi Luca , Salvicchi Alberto , Paladini Piero , Peris Adriano , d’Alessandro Miriana , Cameli Paolo , Bargagli Elena , Tuscany Transplant Group  , Bergantini Laura
Published: December 2022

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40–70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.
Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression
Authors: Esposito Mauro , Gualandi Nicolò , Spirito Giovanni , Ansaloni Federico , Gustincich Stefano , Sanges Remo
Published: December 2022

LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, they could have been positively selected for beneficial cellular functions. Nonetheless, L1 deregulation can be detrimental to the cell, causing diseases such as cancer. The activity of miRNAs represents a fundamental mechanism for controlling transcript levels in somatic cells. These are a class of small non-coding RNAs that cause degradation or translational inhibition of their target transcripts. Beyond this, competitive endogenous RNAs (ceRNAs), mostly made by circular and non-coding RNAs, have been seen to compete for the binding of the same set of miRNAs targeting protein coding genes. In this study, we have investigated whether autonomously transcribed L1s may act as ceRNAs by analyzing public dataset in-silico. We observed that genes sharing miRNA target sites with L1 have a tendency to be upregulated when L1 are overexpressed, suggesting the possibility that L1 might act as ceRNAs. This finding will help in the interpretation of transcriptomic responses in contexts characterized by the specific activation of transposons.
Seventy Years of Treating Delusional Disorder with Antipsychotics: A Historical Perspective
Authors: González-Rodríguez Alexandre , Monreal José A. , Natividad Mentxu , Seeman Mary V.
Published: December 2022

For many decades, delusional disorder (DD) has been considered a treatment-resistant disorder, with antipsychotics acknowledged as the best, though imperfect, treatment. It is possible that the discovery of the right drug could turn treatment resistance into treatment response. The goal of this narrative review is to provide a historical perspective of the treatment of DD since the introduction of antipsychotics 70 years ago. The following search terms were used to scan the literature: antipsychotics AND “delusional disorder”. Findings were that therapy for DD symptoms has changed over time. Initial reports suggested that the drug of choice was the antipsychotic pimozide, and that this drug was especially effective for the somatic subtype of DD. Subsequent studies demonstrated that other antipsychotics, for instance, risperidone and olanzapine, were also highly effective. Treatment response may vary according to the presence or absence of specific symptoms, such as cognitive defect and depression. Clozapine, partial D2 agonists, and long-acting injectable drugs may be more effective than other drugs, but the evidence is not yet in. Because of the absence of robust evidence, treatment guidelines for the optimal management of DD are not yet available.
Investigating the Antibacterial Properties of Prospective Scabicides
Authors: Taylor Sara , Walther Deonne , Fernando Deepani D. , Swe-Kay Pearl , Fischer Katja
Published: December 2022

Scabies is a dermatological disease found worldwide. Mainly in tropical regions, it is also the cause of significant morbidity and mortality due to its association with potentially severe secondary bacterial infections. Current treatment strategies for scabies do not consider the role of opportunistic bacteria, and here we investigate whether current and emerging scabicides can offer any anti-bacterial protection. Using the broth microdilution method, we examined antimicrobial potential of the current scabicide ivermectin and emerging scabies treatments: abametapir, mānuka oil, and its individual β-triketones. Our results demonstrate that the two novel scabicides abametapir and mānuka oil have antimicrobial properties against common scabies-associated bacteria, specifically Staphylococcus aureus, Streptococcus pyogenes, Streptococcus dysgalactiae subsp. equisimilis and Acinetobacter baumannii. The current scabicide ivermectin offers some antimicrobial activity and is capable of inhibiting the growth aforementioned bacteria. This research is important as it could help to inform future best treatment options of scabies, and scabies-related impetigo.
What Are the Roles of Proprotein Convertases in the Immune Escape of Tumors?
Authors: Mehranzadeh Elham , Crende Olatz , Badiola Iker , Garcia-Gallastegi Patricia
Published: December 2022

Protein convertases (PCs) play a significant role in post-translational procedures by transforming inactive precursor proteins into their active forms. The role of PCs is crucial for cellular homeostasis because they are involved in cell signaling. They have also been described in many diseases such as Alzheimer’s and cancer. Cancer cells are secretory cells that send signals to the tumor microenvironment (TME), remodeling the surrounding space for their own benefits. One of the most important components of the TME is the immune system of the tumor. In this review, we describe recent discoveries that link PCs to the immune escape of tumors. Among PCs, many findings have determined the role of Furin (PC3) as a paramount enzyme causing the TME to induce tumor immune evasion. The overexpression of various cytokines and proteins, for instance, IL10 and TGF-B, moves the TME towards the presence of Tregs and, consequently, immune tolerance. Furthermore, Furin is implicated in the regulation of macrophage activity that contributes to the increased impairment of DCs (dendritic cells) and T effector cells. Moreover, Furin interferes in the MHC Class_1 proteolytic cleavage in the trans-Golgi network. In tumors, the T cytotoxic lymphocytes (CTLs) response is impeded by the PD1 receptor (PD1-R) located on CTLs and its ligand, PDL1, located on cancer cells. The inhibition of Furin is a subtle means of enhancing the antitumor response by repressing PD-1 expression in tumors or macrophage cells. The impacts of other PCs in tumor immune escape have not yet been clarified to the extent that Furin has. Accordingly, the influence of other types of PCs in tumor immune escape is a promising topic for further consideration.
New Insights into the Use of Empagliflozin—A Comprehensive Review
Authors: Forycka Joanna , Hajdys Joanna , Krzemińska Julia , Wilczopolski Piotr , Wronka Magdalena , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: December 2022

Empagliflozin is a relatively new drug that, as an inhibitor of the sodium–glucose cotransporter 2 (SGLT2), causes increased urinary glucose excretion and thus contributes to improved glycemic control, better glucose metabolism, reduced glucotoxicity and insulin resistance. Although its original use was to induce a hypoglycemic effect in patients with type 2 diabetes mellitus (T2DM), empagliflozin has also shown a number of other beneficial effects by demonstrating a nephroprotective effect, and it has proven to be a breakthrough in the treatment of heart failure (HF). Empagliflozin has been shown to reduce hospitalizations for HF and the number of deaths from cardiovascular causes. Empagliflozin treatment also reduces the incidence of renal events, including death from renal causes, as well as the risk of end-stage renal failure. Empagliflozin appears to be a fairly well-tolerated and safe drug. In patients with inadequate glycemic control, empagliflozin used in monotherapy or as an adjunct to therapy effectively lowers fasting blood glucose, postprandial blood glucose, average daily glucose levels, glycated hemoglobin A1C (HbA1C) and also leads to significant weight reduction in patients with T2DM. Unfortunately, there are some limitations, e.g., severe hypersensitivity reaction to the drug and a glomerular filtration rate (GFR) < 30 mL/min/1.73 m2. As with any drug, empagliflozin is also characterized by several side effects among which symptomatic hypotension, troublesome genital fungal infections, urinary tract infections and rare ketoacidosis are characteristic.
Re-Analysis of Single-Nucleus Transcriptomics Reveals Diverse Dorsal Root Ganglia Macrophage Responses Following Peripheral Nerve Injury
Authors: Korvenlaita Nea , Louhivuori Lauri
Published: December 2022

An increasing amount of evidence points to an important role of macrophages in peripheral nerve injury (PNI) and associated pain. Peripheral nerve macrophages facilitate the regeneration, while dorsal root ganglia (DRG) macrophages might propagate the injury after a PNI. These differences might be explained by various in vivo models of PNIs or non-uniform methodologies to phenotype the macrophages. Unbiased methods to phenotype macrophages using single whole cell or nucleus transcriptomics have been rarely applied on PNIs outside the nerves themselves. Here, we compare the effects of the transection or crush of the sciatic nerve and spinal nerve transection on the DRG macrophage phenotypes utilizing a publicly available single-nucleus transcriptomic DRG dataset. Our results demonstrate that unique and time-dependent DRG macrophage gene expression profiles were produced by the three PNI models with particular macrophage clusters being enriched that were dependent on the severity of the neuronal injury score. PNI associated DRG macrophages were not purely anti- or pro-inflammatory. These results suggest that various functions of DRG macrophage subtypes are carefully orchestrated upon a PNI. These findings open a new avenue for studying the DRG macrophage subtypes in PNIs and encourage further unbiased phenotyping efforts to better understand their relevance in neuropathic pain.
A Conductance-Based Silicon Synapse Circuit
Authors: Gautam Ashish , Kohno Takashi
Published: December 2022

Neuron, synapse, and learning circuits inspired by the brain comprise the key components of a neuromorphic chip. In this study, we present a conductance-based analog silicon synapse circuit suitable for the implementation of reduced or multi-compartment neuron models. Compartmental models are more bio-realistic. They are implemented in neuromorphic chips aiming to mimic the electrical activities of the neuronal networks in the brain and incorporate biomimetic soma and synapse circuits. Most contemporary low-power analog synapse circuits implement bioinspired “current-based” synaptic models suited for the implementation of single-compartment point neuron models. They emulate the exponential decay profile of the synaptic current, but ignore the effect of the postsynaptic membrane potential on the synaptic current. This dependence is necessary to emulate shunting inhibition, which is thought to play important roles in information processing in the brain. The proposed circuit uses an oscillator-based resistor-type element at its output stage to incorporate this effect. This circuit is used to demonstrate the shunting inhibition phenomenon. Next, to demonstrate that the oscillatory nature of the induced synaptic current has no unforeseen effects, the synapse circuit is employed in a spatiotemporal spike pattern detection task. The task employs the adaptive spike-timing-dependent plasticity (STDP) learning rule, a bio-inspired learning rule introduced in a previous study. The mixed-signal chip is designed in a Taiwan Manufacturing Semiconductor Company 250 nm complementary metal oxide semiconductor technology node. It comprises a biomimetic soma circuit and 256 synapse circuits, along with their learning circuitries.
Effect of Segment Types on Characterization of Soft Sensing Textile Actuators for Soft Wearable Robots
Authors: Yilmaz Ayse Feyza , Khalilbayli Fidan , Ozlem Kadir , Elmoughni Hend M. , Kalaoglu Fatma , Atalay Asli Tuncay , Ince Gökhan , Atalay Ozgur
Published: December 2022

The use of textiles in soft robotics is gaining popularity because of the advantages textiles offer over other materials in terms of weight, conformability, and ease of manufacture. The purpose of this research is to examine the stitching process used to construct fabric-based pneumatic bending actuators as well as the effect of segment types on the actuators’ properties when used in soft robotic glove applications. To impart bending motion to actuators, two techniques have been used: asymmetry between weave and weft knit fabric layers and mechanical anisotropy between these two textiles. The impacts of various segment types on the actuators’ grip force and bending angle were investigated further. According to experiments, segmenting the actuator with a sewing technique increases the bending angle. It was discovered that actuators with high anisotropy differences in their fabric combinations have high gripping forces. Textile-based capacitive strain sensors are also added to selected segmented actuator types, which possess desirable properties such as increased grip force, increased bending angle, and reduced radial expansion. The sensors were used to demonstrate the controllability of a soft robotic glove using a closed-loop system. Finally, we demonstrated that actuators integrated into a soft wearable glove are capable of grasping a variety of items and performing various grasp types.
Overview on Adjunct Ingredients Used in Hydroxyapatite-Based Oral Care Products
Authors: Enax Joachim , Amaechi Bennett T. , Schulze zur Wiesche Erik , Meyer Frederic
Published: December 2022

Hydroxyapatite, Ca5(PO4)3(OH), is a biomimetic active ingredient, which is used in commercial oral care products such as toothpastes and mouthwashes worldwide. Clinical studies (in vivo) as well as in situ and in vitro studies have shown the preventive effects of hydroxyapatite in various field of oral care. In some products, hydroxyapatite is combined with other active ingredients, to achieve an additional antibacterial effect or to promote gum health. This review analyzes the efficacy of six selected natural and nature-inspired ingredients that are commonly used together with hydroxyapatite. These additional actives are either antibacterial (lactoferrin, xylitol, and zinc) or promote gum health (allantoin, bisabolol, and hyaluronic acid). A systematic literature search was performed, and all studies found on each ingredient were analyzed. In summary, all analyzed ingredients mentioned in this review are well described in scientific studies on their beneficial effect for oral health and can be used to expand the preventive effect of hydroxyapatite in oral care products.
A Novel Detachable, Reusable, and Versatile Acoustic Tweezer Manipulation Platform for Biochemical Analysis and Detection Systems
Authors: Liu Yukai , Ji Miaomiao , Zhang Yichi , Qiao Xiaojun , Yu Nanxin , Ding Chenxi , Yang Lingxiao , Feng Rui , Chou Xiujian , Geng Wenping
Published: December 2022

Multifunctional, integrated, and reusable operating platforms are highly sought after in biochemical analysis and detection systems. In this study, we demonstrated a novel detachable, reusable acoustic tweezer manipulation platform that is flexible and versatile. The free interchangeability of different detachable microchannel devices on the acoustic tweezer platform was achieved by adding a waveguide layer (glass) and a coupling layer (polydimethylsiloxane (PDMS) polymer film). We designed and demonstrated the detachable multifunctional acoustic tweezer platform with three cell manipulation capabilities. In Demo I, the detachable acoustic tweezer platform is demonstrated to have the capability for parallel processing and enrichment of the sample. In Demo II, the detachable acoustic tweezer platform with capability for precise cell alignment is demonstrated. In Demo III, it was demonstrated that the detachable acoustic tweezer platform has the capability for the separation and purification of cells. Through experiments, our acoustic tweezer platform has good acoustic retention ability, reusability, and stability. More capabilities can be expanded in the future. It provides a simple, economical, and multifunctional reusable operating platform solution for biochemical analysis and detection systems.
Recent Development of Fluorescent Nanodiamonds for Optical Biosensing and Disease Diagnosis
Authors: Qureshi Shahzad Ahmad , Hsiao Wesley Wei-Wen , Hussain Lal , Aman Haroon , Le Trong-Nghia , Rafique Muhammad
Published: December 2022

The ability to precisely monitor the intracellular temperature directly contributes to the essential understanding of biological metabolism, intracellular signaling, thermogenesis, and respiration. The intracellular heat generation and its measurement can also assist in the prediction of the pathogenesis of chronic diseases. However, intracellular thermometry without altering the biochemical reactions and cellular membrane damage is challenging, requiring appropriately biocompatible, nontoxic, and efficient biosensors. Bright, photostable, and functionalized fluorescent nanodiamonds (FNDs) have emerged as excellent probes for intracellular thermometry and magnetometry with the spatial resolution on a nanometer scale. The temperature and magnetic field-dependent luminescence of naturally occurring defects in diamonds are key to high-sensitivity biosensing applications. Alterations in the surface chemistry of FNDs and conjugation with polymer, metallic, and magnetic nanoparticles have opened vast possibilities for drug delivery, diagnosis, nanomedicine, and magnetic hyperthermia. This study covers some recently reported research focusing on intracellular thermometry, magnetic sensing, and emerging applications of artificial intelligence (AI) in biomedical imaging. We extend the application of FNDs as biosensors toward disease diagnosis by using intracellular, stationary, and time-dependent information. Furthermore, the potential of machine learning (ML) and AI algorithms for developing biosensors can revolutionize any future outbreak.
Review of the Treatments for Central Neuropathic Pain
Authors: Sheldon Breanna L. , Olmsted Zachary T. , Sabourin Shelby , Heydari Ehsaun , Harland Tessa A. , Pilitsis Julie G.
Published: December 2022

Central neuropathic pain (CNP) affects millions worldwide, with an estimated prevalence of around 10% globally. Although there are a wide variety of treatment options available, due to the complex and multidimensional nature in which CNP arises and presents symptomatically, many patients still experience painful symptoms. Pharmaceutical, surgical, non-invasive, cognitive and combination treatment options offer a generalized starting point for alleviating symptoms; however, a more customized approach may provide greater benefit. Here, we comment on the current treatment options that exist for CNP and further suggest the need for additional research regarding the use of biomarkers to help individualize treatment options for patients.
Aβ42 as a Biomarker of Alzheimer’s Disease: Is Saliva a Viable Alternative to Cerebrospinal Fluid?
Authors: Boschi Silvia , Roveta Fausto , Grassini Alberto , Marcinnò Andrea , Cermelli Aurora , Ferrandes Fabio , Rainero Innocenzo , Rubino Elisa
Published: December 2022

The identification of reliable biomarkers in biological fluids is paramount to optimizing the diagnosis of Alzheimer’s disease (AD). Measurement of Aβ42, t-tau, and p-tau in cerebrospinal fluid (CSF) is the most accepted method to support the diagnosis of AD. However, lumbar puncture represents an invasive investigation, whereas saliva is one of the most accessible body fluids. The aim of our study was to investigate salivary concentrations in AD and evaluate the correlation between salivary and CSF Aβ42 concentrations in AD patients, patients with non-AD dementias, and controls. We recruited 100 subjects: 18 AD patients, 64 patients with non-AD dementias, and 18 controls. The mean saliva Aβ42 concentrations in AD patients were higher than in controls (p < 0.001), and to patients with non-AD dementias (p = 0.001). A significant negative correlation between salivary and CSF Aβ42 concentrations was found in the overall group (r = −0.562, p < 0.001) and in non-AD patients (r = −0.443, p < 0.001). Salivary Aβ42 concentrations positively correlated with CSF t-tau (r = 0.321, p = 0.001) and p-tau (r = 0.297, p = 0.001). Our study showed that in AD patients’ saliva, Aβ42 concentrations are specifically increased, and we found an interesting negative correlation between CSF and salivary Aβ42 concentrations that warrants further investigation.
Telemedicine in the Management of Parkinson’s Disease: Achievements, Challenges, and Future Perspectives
Authors: Cubo Esther , Delgado-López Pedro David
Published: December 2022

Background: As the global population grows, there is an increasing demand for neurologic consultation that prompts new ways to reach more patients. Telemedicine can provide an accessible, cost-effective, and high-quality healthcare services. Objectives: In this article, we highlight recent developments, achievements, and challenges regarding outcomes, clinical care, tele-education, teletreatment, teleresearch, and cybersecurity for telemedicine applied to Parkinson´s disease (PD) and other neurological conditions. Results: A growing body of evidence supports the feasibility and effectiveness of telemedicine tools for PD and other movement disorders. Outcome variables regarding satisfaction and efficacy in clinical care and specific issues about education, research, and treatment are reviewed. Additionally, a specific legal framework for teleconsultation has been developed in some centers worldwide. Yet, the implementation of telemedicine is conditioned by the limitations inherent to remote neurological examination, the variable computer usage literacy among patients, and the availability of a reliable internet connection. At present, telemedicine can be considered an additional tool in the clinical management of PD patients. Conclusions: There is an increasing use of remote clinical practice regarding the management of PD and other neurological conditions. Telemedicine is a new and promising tool aimed at special settings and subpopulations.
A Novel Path Generation Approach for Robotic Spatial Printing of Branching Geometry
Authors: Shi Xinyu , Liang Yuan , Phillips Tyson Keen , Zhou Haining , Wan Da , Cui Weijiu , Gao Weijun
Published: December 2022

Although robotic spatial printing (RSP) has demonstrated a new way of fabricating building components with a good stiffness-to-weight ratio, the complexity of the applied geometries is still limited. Among them are branching geometries, which refer to the bio-inspired branching structures (BIBSs) in the building industry. This paper presents a cutting-edge approach to tackle this bottleneck problem, in which we propose an automated printing path generation (APPG) approach for the RSP of branching geometries, including an original hierarchical framework of printing node permutations and a linear workflow that incorporates five core algorithms: the heat method, graph generation, graph traversal, curve adjustment, and lattice generation. Through the execution of this workflow, a lattice structure and its corresponding printing path can be generated. This work is validated by the simulation of three prototypes: two-branch geometry, multi-branch geometry, and multi-level-branch geometry. Printing expenses are compared with each of the related algorithms to validate the efficiency of this proposed approach. Along with the appropriate APPG solutions, an analytical tool for topological type is also presented in this paper.
Shaking Table Test of a Base-Isolated Frame Structure under Near-Fault Ground Motions
Authors: Lyu Qing , Zhu Baijie , Lu Wensheng , Fu Bo , Liu Liangkun , Qian Wei , Zhou Ming , Zhang Zhenya
Published: December 2022

A five-story moment frame structural model with a base isolation system was tested on a shaking table. The isolation system comprised both linear natural rubber bearing (LNR) and nonlinear viscous dampers (NLVDs). Seven ground motions were employed: including three far-fault (FF) and four near-fault (NF) earthquake ground motions. The performance of the isolation system was evaluated by measuring the displacement and base shear of the isolation bearings. Furthermore, the axial force and displacement of the NLVDs were measured. The evolution of the fundamental dynamic frequency of the frame during the test was also determined. During strong earthquakes, NF ground motions caused larger story drifts and floor accelerations of the superstructure than FF ground motions. The displacement and base shear of the isolation base was very large when the isolated structure was subjected to Kobe_TAK000 and ChiChi_TCU102/278 pulse-like NF ground motions. Furthermore, the LNR s experienced tension and uplift when the PGA of input earthquake ground motions was larger than 0.80 g. Although the NLVDs performed very well in combination with the LNRs, the severe responses of the isolation bearings were caused by NF ground motion with a pulse period Tp neighboring the fundamental period of the isolated structure.
Is 24.9 °C Too Hot to Think? A Call to Raise Temperature Setpoints in Australian Offices
Authors: Marzban Samin , Candido Christhina , Brambilla Arianna , Gocer Ozgur , Vijapur Diksha , Jensen Christopher
Published: December 2022

The current +−0.5 PMV (Predicted Mean Vote) targets adopted by NABERS (National Australian Built Environment Rating System) is the practical range deemed acceptable for 90% acceptability for commercial buildings in Australia, however thermal comfort satisfaction scores measured in office buildings still show high percentages of dissatisfied occupants. This paper aims to demonstrate the potential of curbing energy consumption from commercial buildings in Australia by increasing summer temperature set-points. A 10-year NABERS dataset, along with objective and subjective thermal comfort and air quality data from NABERS-certified offices are investigated in this study. Furthermore, different simulation scenarios are tested to investigate the discomfort hours and energy consumption for various summer temperature setpoints. Result analysis shows that occupants’ satisfaction in NABERS-certified buildings was not within the 90% satisfaction, with being too cold/hot as the main source of dissatisfaction. Objective measurements also showed temperature was out of recommended range for several datapoints. Simulation results indicate that, within the average range of 21–24.9 °C, there is not a significant difference in discomfort hours that could drive the selection of one temperature set-point over the other. Challenging the current practices, results suggest that a cooling set point temperature on the upper limit of the range indicated by the Australian standard AS 1837–1976 may minimize the energy consumption without significantly increasing discomfort, or even increasing the perceived satisfaction with the indoor environment.
Similarity Law Study of Shaped Charges Penetrating a Concrete Target
Authors: Zhang Yi , Zhang Xiangru , Zhao Wenda , Hu Feng
Published: December 2022

In order to study the similarity law of penetration of concrete targets by shaped charges, penetration tests of concrete targets with different sizes of shaped-charge jets were carried out, and the prototype and the model projectiles met the similarity law with a simulation ratio of 1:1.5. LS-DYNA finite element software was used to simulate the tests, and the accuracy of the ALE algorithm, fluid–solid coupling algorithm, material model, equation of state, and corresponding material parameters was verified. Numerical simulations were further conducted for the different types of shaped-charge jets (jets, rod jets, and explosively formed projectiles) formed by different liner angles penetrating into the concrete target, and the results show that the shaped-charge jets basically meet the similarity law when penetrating concrete targets.
Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade
Authors: Larroquette Mathieu , Lefort Félix , Heraudet Luc , Bernhard Jean-Christophe , Ravaud Alain , Domblides Charlotte , Gross-Goupil Marine
Published: December 2022

Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival.
Metabolic Risk Factors for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease: A Prospective Study
Authors: Antwi Samuel O. , Craver Emily C. , Nartey Yvonne A. , Sartorius Kurt , Patel Tushar
Published: December 2022

Non-alcoholic fatty liver disease (NAFLD) is a fast-growing public health problem and predisposes to hepatocellular carcinoma (HCC) in a significant proportion of patients. Metabolic alterations might underlie the progression of NAFLD to HCC, but the magnitudes of risk and population-attributable risk fractions (PAFs) for various metabolic conditions that are associated with HCC risk in patients with NAFLD are unknown. We investigated the associations between metabolic conditions and HCC development in individuals with a prior history of NAFLD. The study included 11,245 participants in the SEER-Medicare database, comprising 1310 NAFLD-related HCC cases and 9835 NAFLD controls. We excluded individuals with competing liver diseases (e.g., alcoholic liver disease and chronic viral hepatitis). Baseline pre-existing diabetes mellitus, dyslipidemia, obesity, hypertension, hypothyroidism, and metabolic syndrome were assessed. Multivariable-adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). PAFs were also calculated for each metabolic condition. The results show that diabetes (OR = 2.39, 95% CI: 2.04–2.79), metabolic syndrome (OR = 1.73, 95% CI: 1.49–2.01), and obesity (OR = 1.62, 95% CI: 1.43–1.85) were associated with a higher HCC risk in individuals with NAFLD. The highest PAF for HCC was observed for pre-existing diabetes (42.1%, 95% CI: 35.7–48.5), followed by metabolic syndrome (28.8%, 95% CI: 21.7–35.9) and obesity (13.2%, 95% CI: 9.6–16.8). The major predisposing factors for HCC in individuals with NAFLD are diabetes mellitus, metabolic syndrome, and obesity, and their control would be critically important in mitigating the rising incidence of NAFLD-related HCC.
Pre-Existing Interstitial Lung Abnormalities Are Independent Risk Factors for Interstitial Lung Disease during Durvalumab Treatment after Chemoradiotherapy in Patients with Locally Advanced Non-Small-Cell Lung Cancer
Authors: Daido Wakako , Masuda Takeshi , Imano Nobuki , Matsumoto Naoko , Hamai Kosuke , Iwamoto Yasuo , Takayama Yusuke , Ueno Sayaka , Sumii Masahiko , Shoda Hiroyasu , Ishikawa Nobuhisa , Yamasaki Masahiro , Nishimura Yoshifumi , Kawase Shigeo , Shiota Naoki , Awaya Yoshikazu , Suzuki Tomoko , Kitaguchi Soichi , Fujitaka Kazunori , Nagata Yasushi , Hattori Noboru
Published: December 2022

Introduction/Background: Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments; however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients and Methods: Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. Results: A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70; 95% confidence interval, 1.69–7.72; p < 0.001). Conclusions: We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs.
Loco-Regional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancer Patients Undergoing Front-Line Chemotherapy
Authors: Tinterri Corrado , Sagona Andrea , Barbieri Erika , Di Maria Grimaldi Simone , Jacobs Flavia , Zambelli Alberto , Trimboli Rubina Manuela , Bernardi Daniela , Vinci Valeriano , Gentile Damiano
Published: December 2022

Background: Loco-regional therapy (LRT) in de novo metastatic breast cancer (MBC) has been investigated in several clinical trials, with heterogeneous and conflicting results. Methods: We conducted a retrospective study of de novo MBC patients treated with front-line chemotherapy (FLC) followed by LRT of the primary tumor. Our aims were to evaluate the characteristics, treatment, and oncological outcomes in terms of progression-free survival (PFS), distant progression-free survival (DPFS), and overall survival (OS) of de novo MBC. We also investigated possible subgroups of patients with better outcomes according to menopausal status, biological sub-type, location, number of metastases, and radiologic complete response after FLC. Results: We included 61 patients in the study. After a median follow-up of 55 months, disease progression occurred in 60.7% of patients and 49.2% died. There were no significant differences in PFS, DPFS, and OS between different subgroups of de novo MBC patients. A trend toward better PFS and DPFS was observed in triple-positive tumors, without a statistically significant difference in OS. Conclusions: No specific subgroup of de novo MBC patients showed a statistically significant survival advantage after FLC followed by LRT of the primary tumor.
High-Frequency Nanosecond Bleomycin Electrochemotherapy and its Effects on Changes in the Immune System and Survival
Authors: Balevičiūtė Austėja , Radzevičiūtė Eivina , Želvys Augustinas , Malyško-Ptašinskė Veronika , Novickij Jurij , Zinkevičienė Auksė , Kašėta Vytautas , Novickij Vitalij , Girkontaitė Irutė
Published: December 2022

In this work, a time-dependent and time-independent study on bleomycin-based high-frequency nsECT (3.5 kV/cm × 200 pulses) for the elimination of LLC1 tumours in C57BL/6J mice is performed. We show the efficiency of nsECT (200 ns and 700 ns delivered at 1 kHz and 1 MHz) for the elimination of tumours in mice and increase of their survival. The dynamics of the immunomodulatory effects were observed after electrochemotherapy by investigating immune cell populations and antitumour antibodies at different timepoints after the treatment. ECT treatment resulted in an increased percentage of CD4+ T, splenic memory B and tumour-associated dendritic cell subsets. Moreover, increased levels of antitumour IgG antibodies after ECT treatment were detected. Based on the time-dependent study results, nsECT treatment upregulated PD 1 expression on splenic CD4+ Tr1 cells, increased the expansion of splenic CD8+ T, CD4+CD8+ T, plasma cells and the proportion of tumour-associated pro inflammatory macrophages. The Lin− population of immune cells that was increased in the spleens and tumour after nsECT was identified. It was shown that nsECT prolonged survival of the treated mice and induced significant changes in the immune system, which shows a promising alliance of nanosecond electrochemotherapy and immunotherapy.
Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises
Authors: Skorda Aikaterini , Bay Marie Lund , Hautaniemi Sampsa , Lahtinen Alexandra , Kallunki Tuula
Published: December 2022

Ovarian cancer is the deadliest gynecological cancer, the high-grade serous ovarian carcinoma (HGSC) being its most common and most aggressive form. Despite the latest therapeutical advancements following the introduction of vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors and poly-ADP-ribose-polymerase (PARP) inhibitors to supplement the standard platinum- and taxane-based chemotherapy, the expected overall survival of HGSC patients has not improved significantly from the five-year rate of 42%. This calls for the development and testing of more efficient treatment options. Many oncogenic kinase-signaling pathways are dysregulated in HGSC. Since small-molecule kinase inhibitors have revolutionized the treatment of many solid cancers due to the generality of the increased activation of protein kinases in carcinomas, it is reasonable to evaluate their potential against HGSC. Here, we present the latest concluded and on-going clinical trials on kinase inhibitors in HGSC, as well as the recent work concerning ovarian cancer patient organoids and xenograft models. We discuss the potential of kinase inhibitors as personalized treatments, which would require comprehensive assessment of the biological mechanisms underlying tumor spread and chemoresistance in individual patients, and their connection to tumor genome and transcriptome to establish identifiable subgroups of patients who are most likely to benefit from a given therapy.
Integration of Clinical and CT-Based Radiomic Features for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Systemic Therapy in Breast Cancer
Authors: Tsai Huei-Yi , Tsai Tsung-Yu , Wu Chia-Hui , Chung Wei-Shiuan , Wang Jo-Ching , Hsu Jui-Sheng , Hou Ming-Feng , Chou Ming-Chung
Published: December 2022

The purpose of the present study was to examine the potential of a machine learning model with integrated clinical and CT-based radiomics features in predicting pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) in breast cancer. Contrast-enhanced CT was performed in 329 patients with breast tumors (n = 331) before NST. Pyradiomics was used for feature extraction, and 107 features of seven classes were extracted. Feature selection was performed on the basis of the intraclass correlation coefficient (ICC), and six ICC thresholds (0.7–0.95) were examined to identify the feature set resulting in optimal model performance. Clinical factors, such as age, clinical stage, cancer cell type, and cell surface receptors, were used for prediction. We tried six machine learning algorithms, and clinical, radiomics, and clinical–radiomics models were trained for each algorithm. Radiomics and clinical–radiomics models with gray level co-occurrence matrix (GLCM) features only were also built for comparison. The linear support vector machine (SVM) regression model trained with radiomics features of ICC ≥0.85 in combination with clinical factors performed the best (AUC = 0.87). The performance of the clinical and radiomics linear SVM models showed statistically significant difference after correction for multiple comparisons (AUC = 0.69 vs. 0.78; p < 0.001). The AUC of the radiomics model trained with GLCM features was significantly lower than that of the radiomics model trained with all seven classes of radiomics features (AUC = 0.85 vs. 0.87; p = 0.011). Integration of clinical and CT-based radiomics features was helpful in the pretreatment prediction of pCR to NST in breast cancer.