bluuebunny/crossref_metadata_2025 huggingface dataset:
The Behavior Avoidance Test: Association With Symptom Severity and Treatment Outcome in Obsessive-Compulsive Disorder
Authors: Hansmeier Jana , Haberkamp Anke , Glombiewski Julia A. , Exner Cornelia
Published: December 2021

Behavior therapy of obsessive-compulsive disorder (OCD) aims to reduce avoidance, rituals, and discomfort in OCD-relevant situations. The Behavioral Avoidance Test (BAT) measures these behavior-related outcomes in individually challenging OCD-related situations. The association of the BAT with OCD severity measures and its relevance for treatment outcome is, however, still unclear. The current study investigates with a retrospective analysis of a subsample of a pilot study, (1) if reactions on the BAT are related to OCD severity measures in an OCD sample (n = 28), (2) if treatment with two variants of cognitive-behavior therapy (exposure and response prevention vs. metacognitive therapy) changes the BAT scores and (3) if these changes as well as pretreatment BAT avoidance are relevant for OCD treatment outcome as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Participants rated avoidance, ritual, and discomfort in three individually challenging OCD-related situations before and after therapy. For one of these situations, BAT dimensions were rated by the therapist and an independent rater in addition to the patients' ratings. Correlational analyses found significant correlations between BAT discomfort and OCD severity measures like the Y-BOCS. A repeated measures ANOVA with pre- and posttest scores showed that all three BAT dimensions significantly decreased during both treatments. Hierarchical regression analyses (controlling for Y-BOCS pretest scores) revealed that changes in BAT discomfort as well as pretreatment BAT avoidance scores predicted the Y-BOCS posttest score. These findings suggest that the BAT is a distinct measure of behavior-related outcomes partly being relevant for OCD treatment outcome.
Dancing With Parkinson's Disease: The SI-ROBOTICS Study Protocol
Authors: Bevilacqua Roberta , Benadduci Marco , Bonfigli Anna Rita , Riccardi Giovanni Renato , Melone Giovanni , La Forgia Angela , Macchiarulo Nicola , Rossetti Luca , Marzorati Mauro , Rizzo Giovanna , Di Bitonto Pierpaolo , Potenza Ada , Fiorini Laura , Cortellessa Loizzo Federica Gabriella , La Viola Carlo , Cavallo Filippo , Leone Alessandro , Rescio Gabriele , Caroppo Andrea , Manni Andrea , Cesta Amedeo , Cortellessa Gabriella , Fracasso Francesca , Orlandini Andrea , Umbrico Alessandro , Rossi Lorena , Maranesi Elvira
Published: December 2021

Introduction: Parkinson's disease (PD) is one of the most frequent causes of disability among older people, characterized by motor disorders, rigidity, and balance problems. Recently, dance has started to be considered an effective exercise for people with PD. In particular, Irish dancing, along with tango and different forms of modern dance, may be a valid strategy to motivate people with PD to perform physical activity. The present protocol aims to implement and evaluate a rehabilitation program based on a new system called “SI-ROBOTICS,” composed of multiple technological components, such as a social robotic platform embedded with an artificial vision setting, a dance-based game, environmental and wearable sensors, and an advanced AI reasoner module.

Methods and Analysis: For this study, 20 patients with PD will be recruited. Sixteen therapy sessions of 50 min will be conducted (two training sessions per week, for 8 weeks), involving two patients at a time. Evaluation will be primarily focused on the acceptability of the SI-ROBOTICS system. Moreover, the analysis of the impact on the patients' functional status, gait, balance, fear of falling, cardio-respiratory performance, motor symptoms related to PD, and quality of life, will be considered as secondary outcomes. The trial will start in November 2021 and is expected to end by April 2022.

Discussions: The study aims to propose and evaluate a new approach in PD rehabilitation, focused on the use of Irish dancing, together with a new technological system focused on helping the patient perform the dance steps and on collecting kinematic and performance parameters used both by the physiotherapist (for the evaluation and planning of the subsequent sessions) and by the system (to outline the levels of difficulty of the exercise).

Ethics and Dissemination: The study was approved by the Ethics Committee of the IRCCS INRCA. It was recorded in ClinicalTrials.gov on the number NCT05005208. The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.
A Multi-Directional and Agile Academic Knowledge Transfer Strategy for Healthcare Technology
Authors: Klemme Isabel , Richter Birte , De Sabbata Kevin , Wrede Britta , Vollmer Anna-Lisa
Published: December 2021

Technology, especially cognitive agents and robots, has significant potential to improve the healthcare system and patient care. However, innovation within academia seldomly finds its way into practice. At least in Germany, there is still a digitalization gap between academia and healthcare practice and little understanding of how healthcare facilities can successfully purchase, implement, and adopt new knowledge and technology. Therefore, the aim of this study is to develop a successful academic knowledge transfer strategy for healthcare technology. We conducted a qualitative study with academic staff working in higher education in Germany and professionals in their practice partner organizations. In 15 semi-structured interviews, we aimed to assess interviewees experiences with knowledge transfer, to identify perceived influencing factors, and to understand the key aspects of a successful knowledge transfer strategy. The Dynamic Knowledge Transfer Model by Wehn and Montalvo, 2018 was used for data analysis. Based on our findings, we suggest that a successful transfer strategy between academia and practice needs to be multi-directional and agile. Moreover, partners within the transfer need to be on equal terms about expected knowledge transfer project outcomes. Our proposed measures focus particularly on regular consultations and communication during and after the project proposal phase.
DMSO Concentrations up to 1% are Safe to be Used in the Zebrafish Embryo Developmental Toxicity Assay
Authors: Hoyberghs Jente , Bars Chloé , Ayuso Miriam , Van Ginneken Chris , Foubert Kenn , Van Cruchten Steven
Published: December 2021

Dimethyl sulfoxide (DMSO) is a popular solvent for developmental toxicity testing of chemicals and pharmaceuticals in zebrafish embryos. In general, it is recommended to keep the final DMSO concentration as low as possible for zebrafish embryos, preferably not exceeding 100 μL/L (0.01%). However, higher concentrations of DMSO are often required to dissolve compounds in an aqueous medium. The aim of this study was to determine the highest concentration of DMSO that can be safely used in our standardized Zebrafish Embryo Developmental Toxicity Assay (ZEDTA). In the first part of this study, zebrafish embryos were exposed to different concentrations (0–2%) of DMSO. No increase in lethality or malformations was observed when using DMSO concentrations up to 1%. In a follow-up experiment, we assessed whether compounds that cause no developmental toxicity in the ZEDTA remain negative when dissolved in 1% DMSO, as false positive results due to physiological disturbances by DMSO should be avoided. To this end, zebrafish embryos were exposed to ascorbic acid and hydrochlorothiazide dissolved in 1% DMSO. Negative control groups were also included. No significant increase in malformations or lethality was observed in any of the groups. In conclusion, DMSO concentrations up to 1% can be safely used to dissolve compounds in the ZEDTA.
Chinese Comma Disambiguation in Math Word Problems Using SMOTE and Random Forests
Authors: Huang Jingxiu , Liu Qingtang , Zheng Yunxiang , Wu Linjing
Published: December 2021

Natural language understanding technologies play an essential role in automatically solving math word problems. In the process of machine understanding Chinese math word problems, comma disambiguation, which is associated with a class imbalance binary learning problem, is addressed as a valuable instrument to transform the problem statement of math word problems into structured representation. Aiming to resolve this problem, we employed the synthetic minority oversampling technique (SMOTE) and random forests to comma classification after their hyperparameters were jointly optimized. We propose a strict measure to evaluate the performance of deployed comma classification models on comma disambiguation in math word problems. To verify the effectiveness of random forest classifiers with SMOTE on comma disambiguation, we conducted two-stage experiments on two datasets with a collection of evaluation measures. Experimental results showed that random forest classifiers were significantly superior to baseline methods in Chinese comma disambiguation. The SMOTE algorithm with optimized hyperparameter settings based on the categorical distribution of different datasets is preferable, instead of with its default values. For practitioners, we suggest that hyperparameters of a classification models be optimized again after parameter settings of SMOTE have been changed.
Welcome to Anatomia: A New Open Access Journal
Authors: Fornai Francesco
Published: December 2021

As the Editor-in-Chief, I am honored and pleased to introduce Anatomia (ISSN: 2813-0545) [...]
Correlations among Ultrasonographic, Physicochemical and Sensory Characteristics of Pectoralis Major Muscles in Turkeys Reared in a Sustainable Farming System
Authors: Schwarz Tomasz , Węglarz Andrzej , Andres Krzysztof , Wojtysiak Dorota , Murawski Maciej , Ahmadi Behnaz , Bartlewski Pawel M. , Ahmadi Bahareh
Published: December 2021

This study set out to examine associations among echotextural, physicochemical and sensory attributes of the pectoralis major muscles in 17-week-old organic turkeys (B.U.T. Big-6) varying in the amount of wheat and oat grain in daily feed rations (Group C: complete feed only; Group Exp1: 5–30% of wheat and 0–20% of oat; and Group Exp2: 5–50% of wheat and 0–50% of oat; n = 15 turkeys/group). Digital ultrasonograms of the left pectoral muscle in four different planes (longitudinal-L, transverse-T, and two oblique planes-O1 and O2) were obtained with a 5.0-MHz linear-array transducer just before slaughter. Mean numerical pixel intensity (MPI) and pixel heterogeneity (MPH) of the muscle parenchyma were computed using the ImageProPlus® analytical software. Ten significant correlations between echotextural attributes and various meat characteristics were recorded in Group C, one in Group Exp1, and eight in Group Exp2. When data were pooled for all birds studied, there were twelve significant correlations (p < 0.05); all but one correlation (between MPH and moisture) were for physical and sensory characteristics of meat samples. Computer-assisted analysis is a potential method to determine moisture as well as physical (e.g., coloration) and sensory (e.g., aroma) characteristics of pectoralis major muscles in organic turkeys.
Abortion and Lamb Mortality between Pregnancy Scanning and Lamb Marking for Maiden Ewes in Southern Australia
Authors: Clune Thomas , Lockwood Amy , Hancock Serina , Thompson Andrew N. , Beetson Sue , Campbell Angus J. D. , Glanville Elsa , Brookes Daniel , Trengove Colin , O’Handley Ryan , Kearney Gavin , Jacobson Caroline
Published: December 2021

The contribution of abortions to the overall mortality of lambs born to maiden (primiparous) ewes in Australia remains unclear. This cohort study aimed to quantify abortion and lamb mortality for ewe lambs and maiden Merino two-tooth ewes. Lamb mortality from pregnancy scanning to marking were determined for 19 ewe lamb and 11 Merino two-tooth ewe flocks across southern Australia. Average lamb mortality from scanning to marking was 35.8% (range 14.3–71.1%) for the ewe lambs and 29.4% (range 19.7–52.7%) for the two-tooth ewes. Mid-pregnancy abortion was detected in 5.7% of ewes (range 0–50%) in the ewe lamb flocks and 0.9% of ewes (range 0–4.4%) in the two-tooth ewe flocks. Mid-pregnancy abortion affecting ≥2% of ewes was observed in 6/19 ewe lamb flocks and 2/11 two-tooth ewe flocks. Lamb mortality from birth to marking represented the greatest contributor to foetal and lamb mortality after scanning, but mid-pregnancy abortion was an important contributor to lamb mortality in some ewe lamb flocks. Variability between the flocks indicates scope to improve the overall reproductive performance for maiden ewes by reducing foetal and lamb losses. Addressing mid-pregnancy abortion may improve the reproductive performance in some flocks.
From Feather to Adsorbent: Keratin Extraction, Chemical Modification, and Fe(III) Removal from Aqueous Solution
Authors: Pan Sujuan , Wang Changqing , Wang Yibo , Wang Rongmin
Published: December 2021

In this work, feather keratin was extracted from the waste feather of chicken via alkyd pretreatment and reduction method, the extraction rate is above 85%. The molecular weight and aggregation morphology of feather keratin in an aqueous environment were characterized by 18-angle laser light scattering gel permeation chromatography and field emission transmission electron microscopy. The relationship between the structure and properties of feather keratin is discussed. The 1-(3-dimethylaminopropyl) -3-ethylcarbondiimide hydrochloride and N-hydroxysuccinimide were used as activation system and cross-linkage. The gallic acid was used as modification reagent and was bonded to feather keratin chains; meanwhile, feather keratin chains were cross-linked through covalent bonds obtained the novel adsorbent (named as GA-FK gel). The GA-FK gel was investigated by IR, SEM, TGA, XRD, and BET methods. The results indicated that GA molecules successfully bonded to feather keratin chains and cross-linked between feather keratin chains. The GA-FK gel was found to have a three-dimensional network structure with abundant mesopores. Its pore size range is 1.8~90 nm; average pore size is 19.6 nm. Its specific surface area is 7.17 m2·g−1. In addition, GA-FK gel was applied to remove Fe(III) in water. The maximum adsorption capacity was 319.0 mg·g−1. The adsorption process of GA-FK gel to Fe(III) presents a typical two-stage pattern accompanied with swelling. The adsorption kinetics of GA-FK gel to Fe(III) follows the quasi-second-order model, the adsorption isotherm follows the Freundlich model. Therefore, the adsorption mechanism is non-specific adsorption.
Incorporating Setup Effects into the Reliability Analysis of Driven Piles
Authors: Bian Xiaoya , Chen Jiawei , Bai Xixuan , Zheng Kunpeng
Published: December 2021

Driven-pile setup is referred to a phenomenon in which the bearing capacity of driven piles increases with time after the end of driving (EOD). The setup effect can significantly improve the bearing capacity (ultimate resistance) of driven piles after initial installation, especially the ultimate shaft resistance. Based on the reliability theory and considering the setup effects of driven piles, this article presents an increase factor (Msetup) for the ultimate resistance of driven piles to modify the reliability index calculation formula. At the same time, the correlation between R0 and Rsetup is comprehensively considered in the reliability index calculation. Next, the uncertainty analysis of load and resistance is conducted to determine the ranges of relevant parameters. Meanwhile, the influence of four critical parameters (factor of safety FOS, the ratio of dead load to live load ρ = QD/QL, Msetup, the correlation coefficient between R0 and Rsetup, and ρR0,Rsetup) on reliability index are analyzed. This parametric study indicates that ρ has a slight influence on the reliability index. However, the reliability index is significantly influenced by FOS, Msetup, and ρR0,Rsetup. Finally, by comparisons with the existing results, it is concluded that the formula proposed in this study is reasonable, and more uncertainties are considered to make the calculated reliability index closer to a practical engineering application. The presented formula clearly expresses the incorporation of the pile setup effect into reliability index calculation, and it is conducive to improving the prediction accuracy of the design capacity of driven piles. Therefore, the reliability analysis of driven piles considering setup effects will present a theoretical basis for the application of driven piles in engineering practice.
Computer-Aided Design of Traditional Jigs and Fixtures
Authors: Ibrahim Abdullah D. , Hussein Hussein M. A. , Ahmed Ibrahim , Nasr Emad Abouel , Kamrani Ali , Abdelwahab Sabreen A.
Published: December 2021

Conventional design of jigs and fixtures has become unsuitable given the requirements of modern technology and complexity and diversity in the production with the rapid update of products. Computer-aided design (CAD) of jigs and fixtures is an effective solution in this direction. The current paper focuses on a computer-aided design of the traditional jigs and fixtures and developed a system containing tailor-made software, created using the Visual Basic programming language and installed on it the viewer screen to show the part. The developed system has been built by connecting Visual Basic programming language to the SolidWorks software on which the part is drawn and saved as STEP AP-203 file format, and the system reads and extracts the data from the STEP AP-203 file. Heuristic rules of feature recognition are pre-prepared for checking the extracted geometric data and deciding which data shape will represent the machining feature; then, the system provides the optimum design of the traditional jigs and fixtures for a group of hollow cylindrical parts that contain a group of cross-holes on the cylinder body, whether perpendicular or offset from the cylinder’s axis, (inclined or inclined offset, or blind or through, by applying pre-prepared heuristic rules for the design of traditional jigs and fixtures.
Life-Cycle Oriented Risk Assessment Using a Monte Carlo Simulation
Authors: Züst Simon , Huonder Michael , West Shaun , Stoll Oliver
Published: December 2021

State of the art mechatronic systems are complex assemblies of various parts and sub-systems. In such an interconnected system, even relatively cheap parts can have a major impact on the overall performance due to unexpected failure. Hence, lifecycle management has major implications on the successful modification of existing products. Potential savings due to changes in production and procurement must be compared to the implied risk of products failing in the field due to these changes. This work documents a generic approach for risk assessment based on the distribution of the expected savings and incident costs over the whole lifecycle. To do so, a stochastic model is introduced to quantify the expected savings and costs given a non-risk-free product modification. Using a Monte Carlo simulation, the effects of uncertainty are incorporated into the risk management. The model and simulation are deployed within an industrial use case. The application demonstrates both the appropriateness of the tool and its useability.
Magnetically Deployable Robots Using Layered Lamina Emergent Mechanism
Authors: Giang Tran Nguyen Lam , Cai Catherine Jiayi , Ponraj Godwin , Ren Hongliang
Published: December 2021

The steady rise of deployable structures and mechanisms based on kirigami and origami principles has brought about design innovations that yield flexible and lightweight robots. These robots are designed based on desirable locomotion mechanisms and often incorporate additional materials to support their flexible structure to enable load-bearing applications and considerable efficient movement. One tetherless way to actuate these robots is via the use of magnets. This paper incorporates magnetic actuation and kirigami structures based on the lamina emergent mechanism (LEM). Three designs of magnetic-actuated LEMs (triangular prism, single LEM (SLEM), alternating mirror dual LEM (AMDLEM)) are proposed, and small permanent magnets are attached to the structures’ flaps or legs that rotate in response to an Actuating Permanent Magnet (APM) to yield stick-slip locomotion, enabling the robots to waddle and crawl on a frictional surface. For preliminary characterization, we actuate the three designs at a frequency of 0.6 Hz. We observed the triangular prism, SLEM, and AMDLEM prototypes to achieve horizontal speeds of 4.3 mm/s, 10.7 mm/s, and 12.5 mm/s on flat surfaces, respectively. We further explore how changing different parameters (actuation frequency, friction, leg length, stiffness, compressibility) affects the locomotion of the different mechanisms.
Circuit Breakers in Low- and Medium-Voltage DC Microgrids for Protection against Short-Circuit Electrical Faults: Evolution and Future Challenges
Authors: Perea-Mena Bayron , Valencia-Velasquez Jaime A. , López-Lezama Jesús M. , Cano-Quintero Juan B. , Muñoz-Galeano Nicolás
Published: December 2021

This paper deals with circuit breakers (CBs) used in direct current microgrids (DCMGs) for protection against electrical faults, focusing on their evolution and future challenges in low voltage (<1.5 kV) and medium voltage (between 1.5 kV and 20 kV). In recent years, proposals for new circuit-breaker features have grown. Therefore, a review on the evolution of circuit breakers for DCMGs is of utmost importance. In general terms, this paper presents a review concerning the evolution of circuit breakers used in DCMGs, focusing on fuses, mechanical circuit breakers (MCBs), solid-state circuit breakers (SSCBs), and hybrid circuit breakers (HCBs). Their evolution is presented highlighting the advantages and disadvantages of each device. It was found that although modern circuit breakers have begun to be commercially available, many of them are still under development; consequently, some traditional fuses and MCBs are still common in DCMGs, but under certain restrictions or limitations. Future challenges that would allow a successful and adequate implementation of circuit breakers in DCMGs are also presented.
Effects of Porcine Whole-Blood Protein Hydrolysate on Exercise Function and Skeletal Muscle Differentiation
Authors: Jin Sun Woo , Lee Gi Ho , Kim Ji Yeon , Kim Chae Yeon , Choo Young Moo , Cho Whajung , Choi Jae Ho , Han Eun Hee , Hwang Yong Pil , Jeong Hye Gwang
Published: December 2021

A number of studies have utilized blood waste as a bioresource by enzymatic hydrolysis to obtain amino acids, such as branched-chain amino acids, which can increase muscle mass or prevent muscle loss during weight loss. Although a significantly high content of branched-chain amino acids has been reported in porcine whole-blood protein hydrolysate (PWBPH), the effects of PWBPH on skeletal muscle differentiation and exercise function remain unclear. In this study, we investigated the effects of PWBPH on exercise endurance in ICR mice and muscle differentiation in C2C12 mouse myoblasts and gastrocnemius (Gas) muscle of mice. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased the time to exhaustion on a treadmill. PWBPH also increased the Gas muscle weight to body weight ratio. In addition, PWBPH treatment increased skeletal muscle differentiation proteins and promoted the Akt/mTOR-dependent signaling pathway in vitro and in vivo. These results suggest that PWBPH can be utilized as a bioresource to enhance exercise function and skeletal muscle differentiation.
Promising Cr-Doped ZnO Nanorods for Photocatalytic Degradation Facing Pollution
Authors: H. Alkallas Fatemah. , Ben Gouider Trabelsi Amira , Nasser Ramzi , Fernandez Susana , Song Ji-Ming , Elhouichet Habib
Published: December 2021

Chromium (Cr)-doped zinc oxide (ZnO) nanorods with wurtzite hexagonal structure were prepared through a thermal decomposition technique. The concentration effect of the Cr doping on the structural, morphological, and optical properties of the ZnO nanorods was established by correlating various measurements: transmission electron microscopy (TEM), photoluminescence (PL), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and several UV-visible studies. The obtained nanorods were investigated as photocatalysts for the photodegradation process of methyl orange (MO), under UV-vis light illumination. Different weights and time intervals were studied. A 99.8% photodegradation of MO was obtained after 100 min in the presence of 1 wt.% Cr III acetate hydroxide and zinc acetate dehydrate “ZnO-Cr1”. The kinetic rate constant of the reaction was found to be equal to 4.451 × 10−2 min−1 via a pseudo-first order rate model. Scavenger radicals demonstrated the domination of OH• radicals by those of O2•− superoxide species during the photodegradation. The interstitial oxygen site Oi is proposed to play a key role in the generation of holes in the valence band under visible irradiation. The ZnO-Cr1 photocatalyst displayed good cycling stability and reusability.
Whole-Genome Transcript Expression Profiling Reveals Novel Insights into Transposon Genes and Non-Coding RNAs during Atlantic Salmon Seawater Adaptation
Authors: Valenzuela-Muñoz Valentina , Gallardo-Escárate Cristian , Benavente Bárbara P. , Valenzuela-Miranda Diego , Núñez-Acuña Gustavo , Escobar-Sepulveda Hugo , Váldes Juan Antonio
Published: December 2021

The growing amount of genome information and transcriptomes data available allows for a better understanding of biological processes. However, analysis of complex transcriptomic experimental designs involving different conditions, tissues, or times is relevant. This study proposes a novel approach to analyze complex data sets combining transcriptomes and miRNAs at the chromosome-level genome. Atlantic salmon smolts were transferred to seawater under two strategies: (i) fish group exposed to gradual salinity changes (GSC) and (ii) fish group exposed to a salinity shock (SS). Gills, intestine, and head kidney samples were used for total RNA extraction, followed by mRNA and small RNA illumina sequencing. Different expression patterns among the tissues and treatments were observed through a whole-genome transcriptomic approach. Chromosome regions highly expressed between experimental conditions included a great abundance of transposable elements. In addition, differential expression analysis showed a greater number of transcripts modulated in response to SS in gills and head kidney. miRNA expression analysis suggested a small number of miRNAs involved in the smoltification process. However, target analysis of these miRNAs showed a regulatory role in growth, stress response, and immunity. This study is the first to evidence the interplaying among mRNAs and miRNAs and the structural relationship at the genome level during Atlantic salmon smoltification.
Assessments of the Ecological and Health Risks of Potentially Toxic Metals in the Topsoils of Different Land Uses: A Case Study in Peninsular Malaysia
Authors: Yap Chee Kong , Chew Weiyun , Al-Mutairi Khalid Awadh , Nulit Rosimah , Ibrahim Mohd. Hafiz , Wong Koe Wei , Bakhtiari Alireza Riyahi , Sharifinia Moslem , Ismail Mohamad Saupi , Leong Wah June , Tan Wen Siang , Cheng Wan Hee , Okamura Hideo , You Chen Feng , Al-Shami Salman Abdo
Published: December 2021

Human activities due to different land uses are being studied widely in many countries. This study aimed to determine the ecological risks and human health risk assessments (HHRA) of Cd, Pb, Ni, Cu, and Zn in the topsoils of six land uses in Peninsular Malaysia. The ranges of the potentially toxic metals (PTMs) in the soils (mg/kg, dry weight) of this study were 0.24–12.43 for Cd (mean: 1.94), 4.66–2363 for Cu (mean: 228), 2576–116,344 for Fe (mean: 32,618), 2.38–75.67 for Ni (mean: 16.04), 7.22–969 for Pb (mean: 115) and 11.03–3820 for Zn (mean: 512). For the ecological risk assessments, the potential ecological risk index (PERI) for single metals indicated that the severity of pollution of the five metals decreased in the following sequence: Cd > Cu > Pb > Zn > Ni. It was found that industry, landfill, rubbish heap, and mining areas were categorized as “very high ecological risk”. For HHRA, the land uses of industry, landfill and rubbish heap were found to have higher hazard quotient (HQ) values for the three pathways (with the order: ingestion > dermal contact > inhalation ingestion) of the five metals for children and adults, when compared to the mining, plantation, and residential areas. The values for both the non-carcinogenic (Cd, Cu, Ni, and Zn), and carcinogenic risks (CR) for inhalation (Cd and Ni) obtained for children and adults in this study showed no serious adverse health impacts on their health. However, of public concern, the hazard index (HI), for Pb of children at the landfill (L-3) and the rubbish heap (RH-3) sites exceeded 1.0, indicating non-carcinogenic risk (NCR) for children. Therefore, these PERI and HHRA results provided fundamental data for PTMs pollution mitigation and environmental management in areas of different land uses in Peninsular Malaysia.
Emerging Nanoparticle Strategies for Modulating Tumor-Associated Macrophage Polarization
Authors: Shi Lu , Gu Hongchen
Published: December 2021

Immunotherapy has made great progress in recent years, yet the efficacy of solid tumors remains far less than expected. One of the main hurdles is to overcome the immune-suppressive tumor microenvironment (TME). Among all cells in TME, tumor-associated macrophages (TAMs) play pivotal roles because of their abundance, multifaceted interactions to adaptive and host immune systems, as well as their context-dependent plasticity. Underlying the highly plastic characteristic, lots of research interests are focused on repolarizing TAMs from M2-like pro-tumor phenotype towards M1-like antitumoral ones. Nanotechnology offers great opportunities for targeting and modulating TAM polarization to mount the therapeutic efficacy in cancer immunotherapy. Here, this mini-review highlights those emerging nano-approaches for TAM repolarization in the last three years.
TRP Channels as Molecular Targets to Relieve Cancer Pain
Authors: Duitama Milena , Moreno Yurany , Santander Sandra Paola , Casas Zulma , Sutachan Jhon Jairo , Torres Yolima P. , Albarracín Sonia L.
Published: December 2021

Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.
Role of IL-10-Producing Natural Killer Cells in the Regulatory Mechanisms of Inflammation during Systemic Infection
Authors: Martinez-Espinosa Israel , Serrato José A. , Ortiz-Quintero Blanca
Published: December 2021

Natural killer (NK) cells have the dual ability to produce pro-inflammatory (IFNγ) and anti-inflammatory (IL-10) cytokines during systemic infection, which points to their crucial role both as inflammatory effectors for infection clearance and as regulators to counterbalance inflammation to limit immune-mediated damage to the host. In particular, immunosuppressive IL-10 secretion by NK cells has been described to occur in systemic, but not local, infections as a recent immunoregulatory mechanism of inflammation that may be detrimental or beneficial, depending on the timing of release, type of disease, or the infection model. Understanding the factors that drive the production of IL-10 by NK cells and their impact during dualistic inflammatory states, such as sepsis and other non-controlled inflammatory diseases, is relevant for achieving effective therapeutic advancements. In this review, the evidence regarding the immunoregulatory role of IL-10-producing NK cells in systemic infection is summarized and discussed in detail, and the potential molecular mechanisms that drive IL-10 production by NK cells are considered.
Diagnostic and Therapeutic Values of Angiogenic Factors in Endometrial Cancer
Authors: Roškar Luka , Roškar Irena , Rižner Tea Lanišnik , Smrkolj Špela
Published: December 2021

Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and requires a relatively invasive diagnostic evaluation and operative therapy as the primary therapeutic approach. Angiogenesis is one of the main processes needed for cancer growth and spread. The production of angiogenic factors (AFs) appears early in the process of carcinogenesis. The detection of AFs in plasma and tissue and a better understanding of the angiogenic properties of EC may contribute not only to earlier but also more specific diagnosis and consequently tailored and individual therapeutic approaches. AFs and their receptors also have high potential as binding sites for targeted cancer therapy. In this review, we discuss angiogenesis in EC and the characteristics of the AFs that most contribute to angiogenesis in EC. We also highlight therapeutic strategies that target angiogenesis as potential EC therapy.
Chitin- and Chitosan-Based Composite Materials
Authors: Aranaz Inmaculada , Acosta Niuris
Published: December 2021

Chitin and its deacetylated derivative chitosan are amino polysaccharides of great interest due to their biological and technological properties [...]
Neural Correlates of Letter and Semantic Fluency in Primary Progressive Aphasia
Authors: Riello Marianna , Frangakis Constantine E. , Ficek Bronte , Webster Kimberly T. , Desmond John E. , Faria Andreia V. , Hillis Argye E. , Tsapkini Kyrana
Published: December 2021

Verbal fluency (VF) is an informative cognitive task. Lesion and functional imaging studies implicate distinct cerebral areas that support letter versus semantic fluency and the understanding of neural and cognitive mechanisms underlying task performance. Most lesion studies include chronic stroke patients. People with primary progressive aphasia (PPA) provide complementary evidence for lesion-deficit associations, as different brain areas are affected in stroke versus PPA. In the present study we sought to determine imaging, clinical and demographic correlates of VF in PPA. Thirty-five patients with PPA underwent an assessment with letter and category VF tasks, evaluation of clinical features and an MRI scan for volumetric analysis. We used stepwise regression models to determine which brain areas are associated with VF performance while acknowledging the independent contribution of clinical and demographic factors. Letter fluency was predominantly associated with language severity (R2 = 38%), and correlated with the volume of the left superior temporal regions (R2 = 12%) and the right dorsolateral prefrontal area (R2 = 5%). Semantic fluency was predominantly associated with dementia severity (R2 = 47%) and correlated with the volume of the left inferior temporal gyrus (R2 = 7%). No other variables were significantly associated with performance in the two VF tasks. We concluded that, independently of disease severity, letter fluency is significantly associated with the volume of frontal and temporal areas whereas semantic fluency is associated mainly with the volume of temporal areas. Furthermore, our findings indicated that clinical severity plays a critical role in explaining VF performance in PPA, compared to the other clinical and demographic factors.
From Shunt to Recovery: A Multidisciplinary Approach to Hydrocephalus Treatment in Severe Acquired Brain Injury Rehabilitation
Authors: Castellani Giovanna B. , Miccoli Giovanni , Cava Francesca C. , Salucci Pamela , Colombo Valentina , Maietti Elisa , Palandri Giorgio
Published: December 2021

Background: Hydrocephalus among Severe Acquired Brain Injury (SABI) patients remains overlooked during rehabilitation. Methods: A retrospective cohort study was carried out of traumatic and non-traumatic SABI patients with hydrocephalus, consecutively admitted over 9 years in a tertiary referral specialized rehabilitation hospital. Patients were treated with ventriculoperitoneal shunt before or during inpatient rehabilitation and assessed using the Level of Cognitive Functioning Scale and Disability Rating Scale. Logistic regression models were used to identify predictors of post-surgical complications. Linear regression models were used to investigate predictors of hospital length of stay (LOS), disability, and cognitive function. Results: Of the 82 patients, 15 had post-surgical complications and 16 underwent cranioplasty. Shunt placement complication risk was higher when fixed vs. when programmable pressure valves were used. A total of 56.3% achieved functional improvement at discharge and 88.7% improved in cognitive function; of the 82 patients, 56% were discharged home. In multiple regression analyses, higher disability at discharge was related to cranioplasty and longer LOS, while poorer cognitive function was associated with cranioplasty. Increase in LOS was associated with increasing time to shunt and decreasing age. Conclusions: A significant improvement in cognitive and functional outcomes can be achieved. Cranioplasty increased LOS, and fixed pressure valves were related to poorer outcomes.
Systemic Triple Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Ready for Prime Time or Still to Be Explored?
Authors: Thomas Christian , Baunacke Martin , Erb Holger H. H. , Füssel Susanne , Erdmann Kati , Putz Juliane , Borkowetz Angelika
Published: December 2021

For decades, mono androgen deprivation therapy (ADT) has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last seven years demonstrating a significant survival advantage by combination treatment with standard ADT plus docetaxel or androgen receptor-axis-targeted therapy (ARAT) compared to ADT monotherapy. As a result, overall survival can be prolonged by at least 18 months. Recently published congress data of the PEACE-1 study suggests that in the future, triple therapy might be the new gold standard. In addition to this study, which has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel, several other phase III triple therapy studies are currently ongoing. The different modes of action that are investigated reach from AR-targeting over mitotic inhibition and immunotherapy to PARP and AKT inhibition. In this review we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.
Prognostic Impact of the SARC-F Score in Gastrointestinal Advanced Cancers
Authors: Matsui Masahiro , Nishikawa Hiroki , Goto Masahiro , Asai Akira , Ushiro Kosuke , Ogura Takeshi , Takeuchi Toshihisa , Nakamura Shiro , Kakimoto Kazuki , Miyazaki Takako , Fukunishi Shinya , Ohama Hideko , Yokohama Keisuke , Yasuoka Hidetaka , Higuchi Kazuhide
Published: December 2021

We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0–2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.
Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53WT Uterine Leiomyosarcoma
Authors: Chamberlain Victoria , Drew Yvette , Lunec John
Published: December 2021

As there is no optimal therapeutic strategy defined for women with advanced or recurrent uLMS, there is an urgent need for the discovery of novel, targeted approaches. One such area of interest is the pharmacological inhibition of the MDM2-p53 interaction with small-molecular-weight MDM2 inhibitors. Growth inhibition and cytotoxic assays were used to evaluate uLMS cell line responses to MDM2 inhibitors as single agents and in combination, qRT-PCR to assess transcriptional changes and Caspase-Glo 3/7 assay to detect apoptosis. RG7388 and HDM201 are potent, selective antagonists of the MDM2-p53 interaction that can effectively stabilise and activate p53 in a dose-dependent manner. GSK2830371, a potent and selective WIP1 phosphatase inhibitor, was shown to significantly potentiate the growth inhibitory effects of RG7388 and HDM201, and significantly increase the mRNA expression of p53 transcriptional target genes in a p53WT cell line at a concentration that has no growth inhibitory effects as a single agent. RG7388, HDM201 and GSK2830371 failed to induce apoptosis as single agents; however, a combination treatment tipped cells into apoptosis from senescence. These data present the possibility of MDM2 and WIP1 inhibitor combinations as a potential treatment option for p53WT uLMS patients that warrants further investigation.
Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study
Authors: Kang Chung-Jan , Wen Yu-Wen , Lee Shu-Ru , Lee Li-Yu , Hsueh Chuen , Lin Chien-Yu , Fan Kang-Hsing , Wang Hung-Ming , Hsieh Chia-Hsun , Ng Shu-Hang , Yeh Chih-Hua , Lin Chih-Hung , Tsao Chung-Kan , Fang Tuan-Jen , Huang Shiang-Fu , Lee Li-Ang , Fang Ku-Hao , Yen Tzu-Chen , Cheng Nai-Ming , Tsai Tsung-You , Tai Shiao-Fwu , Tsai Chi-Ying
Published: December 2021

(1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1–4 and > 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1–4 mm) were significantly lower than those observed in patients with clear margins (> 4 mm; all p values < 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins (>4 mm) should be considered a key surgical goal to improve outcomes in this patient group.
IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells
Authors: Domagala Marcin , Ysebaert Loïc , Ligat Laetitia , Lopez Frederic , Fournié Jean-Jacques , Laurent Camille , Poupot Mary
Published: December 2021

Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an “M1-like phenotype”. We show here that their reprogramming towards an M2-like phenotype (tumor-supportive) with IL-10 leads to an increase in leukemic cell survival. Inflammatory cytokines, such as TNF, are also able to depolarize M2-type protective NLC (decreasing CLL cell viability), an effect which is countered by IL-10 or blocking antibodies. Interestingly, both IL-10 and TNF are implied in the pathophysiology of CLL and their elevated level is associated with bad prognosis. We propose that the molecular balance between these two cytokines in CLL niches plays an important role in the maintenance of the protective phenotype of NLCs, and therefore in the survival of CLL cells.
Identification of Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer by Fourier-Transform Infrared Micro-Imaging
Authors: Mazza Camille , Gaydou Vincent , Eymard Jean-Christophe , Birembaut Philippe , Untereiner Valérie , Côté Jean-François , Brocheriou Isabelle , Coeffic David , Villena Philippe , Larré Stéphane , Vuiblet Vincent , Piot Olivier
Published: December 2021

Background: Neoadjuvant chemotherapy (NAC) improves survival in responder patients. However, for non-responders, the treatment represents an ineffective exposure to chemotherapy and its potential adverse events. Predicting the response to treatment is a major issue in the therapeutic management of patients, particularly for patients with muscle-invasive bladder cancer. Methods: Tissue samples of trans-urethral resection of bladder tumor collected at the diagnosis time, were analyzed by mid-infrared imaging. A sequence of spectral data processing was implemented for automatic recognition of informative pixels and scoring each pixel according to a continuous scale (from 0 to 10) associated with the response to NAC. The ground truth status of the responder or non-responder was based on histopathological examination of the samples. Results: Although the TMA spots of tumors appeared histologically homogeneous, the infrared approach highlighted spectral heterogeneity. Both the quantification of this heterogeneity and the scoring of the NAC response at the pixel level were used to construct sensitivity and specificity maps from which decision criteria can be extracted to classify cancerous samples. Conclusions: This proof-of-concept appears as the first to evaluate the potential of the mid-infrared approach for the prediction of response to neoadjuvant chemotherapy in MIBC tissues.