bluuebunny/crossref_metadata_2025 huggingface dataset:
AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew
Authors: Auyez Almira , Sayan A. Emre , Kriajevska Marina , Tulchinsky Eugene
Published: September 2021

The TAM proteins TYRO3, AXL, and MER are receptor tyrosine kinases implicated in the clearance of apoptotic debris and negative regulation of innate immune responses. AXL contributes to immunosuppression by terminating the Toll-like receptor signaling in dendritic cells, and suppressing natural killer cell activity. In recent years, AXL has been intensively studied in the context of cancer. Both molecules, the receptor, and its ligand GAS6, are commonly expressed in cancer cells, as well as stromal and infiltrating immune cells. In cancer cells, the activation of AXL signaling stimulates cell survival and increases migratory and invasive potential. In cells of the tumour microenvironment, AXL pathway potentiates immune evasion. AXL has been broadly implicated in the epithelial-mesenchymal plasticity of cancer cells, a key factor in drug resistance and metastasis. Several antibody-based and small molecule AXL inhibitors have been developed and used in preclinical studies. AXL inhibition in various mouse cancer models reduced metastatic spread and improved the survival of the animals. AXL inhibitors are currently being tested in several clinical trials as monotherapy or in combination with other drugs. Here, we give a brief overview of AXL structure and regulation and discuss the normal physiological functions of TAM receptors, focusing on AXL. We present a theory of how epithelial cancers exploit AXL signaling to resist cytotoxic insults, in order to disseminate and relapse.
1.5T Magnetic Resonance-Guided Stereotactic Body Radiotherapy for Localized Prostate Cancer: Preliminary Clinical Results of Clinician- and Patient-Reported Outcomes
Authors: Poon Darren M. C. , Yuan Jing , Wong Oi-Lei , Yang Bin , Chiu Sin-Ting , Cheung Kin-Yin , Chiu George , Yu Siu-Ki
Published: September 2021

Background: Magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) offers the potential for achieving better prostate cancer (PC) treatment outcomes. This study reports the preliminary clinical results of 1.5T MRgSBRT in localized PC, based on both clinician-reported outcome measurement (CROM) and patient-reported outcome measurement (PROM). Methods: Fifty-one consecutive localized PC patients were prospectively enrolled with a median follow-up of 199 days. MRgSBRT was delivered in five fractions of 7.25–8 Gy with daily online adaptation. Clinician-reported gastrointestinal (GI) and genitourinary (GU) adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) Scale v. 5.0 were assessed. The Expanded Prostate Cancer Index Composite Questionnaire was collected at baseline, 1 month, and every 3 months thereafter. Serial prostate-specific antigen measurements were longitudinally recorded. Results: The maximum cumulative clinician-reported grade ≥ 2 acute GU and GI toxicities were 11.8% (6/51) and 2.0% (1/51), respectively, while grade ≥ 2 subacute GU and GI toxicities were 2.3% (1/43) each. Patient-reported urinary, bowel, and hormonal domain summary scores were reduced at 1 month, then gradually returned to baseline levels, with the exception of the sexual domain. Domain-specific subscale scores showed similar longitudinal changes. All patients had early post-MRgSBRT biochemical responses. Conclusions: The finding of low toxicity supports the accumulation of clinical evidence for 1.5T MRgSBRT in localized PC.
The Burden of Late Effects and Related Risk Factors in Adolescent and Young Adult Cancer Survivors: A Scoping Review
Authors: Ryder-Burbidge Charlotte , Diaz Ruth L. , Barr Ronald D. , Gupta Sumit , Nathan Paul C. , McKillop Sarah J. , Fidler-Benaoudia Miranda M.
Published: September 2021

Risk factors associated with late effects in survivors of adolescent and young adult (AYA) cancer are poorly understood. We conducted a systematic scoping review to identify cohort studies published in English from 2010–2020 that included: (1) cancer survivors who were AYAs (age 15–39 years) at diagnosis and (2) outcomes of subsequent malignant neoplasms (SMNs), chronic conditions, and/or late mortality (>5 years postdiagnosis). There were 652 abstracts identified and, ultimately, 106 unique studies were included, of which 23, 34, and 54 studies related to the risk of SMNs, chronic conditions, and mortality, respectively. Studies investigating late effects among survivors of any primary cancer reported that AYA cancer survivors were at higher risk of SMN, chronic conditions, and all-cause mortality compared to controls. There was an indication that the following factors increased risk: radiation exposure (n = 3) for SMNs; younger attained age (n = 4) and earlier calendar period of diagnosis (n = 3) for chronic conditions; and non-Hispanic Black or Hispanic (n = 5), low socioeconomic status (n = 3), and earlier calendar period of diagnosis (n = 4) for late mortality. More studies including the full AYA age spectrum, treatment data, and results stratified by age, sex, and cancer type are needed to advance knowledge about late effects in AYA cancer survivors.
Gamma Carbonic Anhydrases from Hydrothermal Vent Bacteria: Cases of Alternating Active Site Due to a Long Loop with Proton Shuttle Residue
Authors: Manyumwa Colleen Varaidzo , Tastan Bishop Özlem
Published: September 2021

Accelerated CO2 sequestration uses carbonic anhydrases (CAs) as catalysts; thus, there is much research on these enzymes. The γ-CA from Escherichia coli (EcoCA-γ) was the first γ-CA to display an active site that switches between “open” and “closed” states through Zn2+ coordination by the proton-shuttling His residue. Here, we explored this occurrence in γ-CAs from hydrothermal vent bacteria and also the γ-CA from Methanosarcina thermophila (Cam) using molecular dynamics. Ten sequences were analyzed through multiple sequence alignment and motif analysis, along with three others from a previous study. Conservation of residues and motifs was high, and phylogeny indicated a close relationship amongst the sequences. All structures, like EcoCA-γ, had a long loop harboring the proton-shuttling residue. Trimeric structures were modeled and simulated for 100 ns at 423 K, with all the structures displaying thermostability. A shift between “open” and “closed” active sites was observed in the 10 models simulated through monitoring the behavior of the His proton-shuttling residue. Cam, which has two Glu proton shuttling residues on long loops (Glu62 and Glu84), also showed an active site switch affected by the first Glu proton shuttle, Glu62. This switch was thus concluded to be common amongst γ-CAs and not an isolated occurrence.
Pd/Alumina Catalysts for Beneficial Transformation of Harmful Freon R-22
Authors: Radlik Monika , Juszczyk Wojciech , Kemnitz Erhard , Karpiński Zbigniew
Published: September 2021

Chlorodifluoromethane (R-22), the most abundant freon in the atmosphere, was subjected to successful hydrodechlorination in the presence of palladium supported on γ-alumina, at a relatively low reaction temperature (180 °C). The combination of catalytic actions of alumina (performing freon dismutation) and Pd nanoparticles (catalyzing C–Cl bond splitting in the presence of hydrogen) results in the transformation of freon into valuable, chlorine-free products: methane and fluoroform, the mixture of which is used in plasma etching of silicon and silicon nitride. Very highly metal dispersed Pt/Al2O3 catalysts, with metal particles of ~1.3 nm in size, are not as effective as Pd/Al2O3, resulting in only partial dechlorination. A long-term dechlorination screening (3–4 days) showed good catalytic stability of Pd/alumina catalysts.
Zonula occludens 2 and Cell-Cell Contacts Are Required for Normal Nuclear Shape in Epithelia
Authors: Hernández-Guzmán Christian , Gallego-Gutiérrez Helios , Chávez-Munguía Bibiana , Martín-Tapia Dolores , González-Mariscal Lorenza
Published: September 2021

MAGUK protein ZO-2 is present at tight junctions (TJs) and nuclei. In MDCK ZO-2 knockdown (KD) cells, nuclei exhibit an irregular shape with lobules and indentations. This condition correlates with an increase in DNA double strand breaks, however cells are not senescent and instead become resistant to UV-induced senescence. The irregular nuclear shape is also observed in isolated cells and in those without TJs, due to the lack of extracellular calcium. The aberrant nuclear shape of ZO-2 KD cells is not accompanied by a reduced expression of lamins A/C and B and lamin B receptors. Instead, it involves a decrease in constitutive and facultative heterochromatin, and microtubule instability that is restored with docetaxel. ZO-2 KD cells over-express SUN-1 that crosses the inner nuclear membrane and connects the nucleoskeleton of lamin A to nesprins, which traverse the outer nuclear membrane. Nesprins-3 and -4 that indirectly bind on their cytoplasmic face to vimentin and microtubules, respectively, are also over-expressed in ZO-2 KD cells, whereas vimentin is depleted. SUN-1 and lamin B1 co-immunoprecipitate with ZO-2, and SUN-1 associates to ZO-2 in a pull-down assay. Our results suggest that ZO-2 forms a complex with SUN-1 and lamin B1 at the inner nuclear membrane, and that ZO-2 and cell–cell contacts are required for a normal nuclear shape.
Viroids, and the Legacy of Ricardo Flores (1947–2020)
Authors: Hadidi Ahmed , Randles John W.
Published: September 2021

Viroids were discovered by Diener in 1971 [...]
Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels
Authors: Vaiciuleviciute Raminta , Bironaite Daiva , Uzieliene Ilona , Mobasheri Ali , Bernotiene Eiva
Published: September 2021

Osteoarthritis (OA) and cardiovascular diseases (CVD) share many similar features, including similar risk factors and molecular mechanisms. A great number of cardiovascular drugs act via different ion channels and change ion balance, thus modulating cell metabolism, osmotic responses, turnover of cartilage extracellular matrix and inflammation. These drugs are consumed by patients with CVD for many years; however, information about their effects on the joint tissues has not been fully clarified. Nevertheless, it is becoming increasingly likely that different cardiovascular drugs may have an impact on articular tissues in OA. Here, we discuss the potential effects of direct and indirect ion channel modulating drugs, including inhibitors of voltage gated calcium and sodium channels, hyperpolarization-activated cyclic nucleotide-gated channels, β-adrenoreceptor inhibitors and angiotensin-aldosterone system affecting drugs. The aim of this review was to summarize the information about activities of cardiovascular drugs on cartilage and subchondral bone and to discuss their possible consequences on the progression of OA, focusing on the modulation of ion channels in chondrocytes and other joint cells, pain control and regulation of inflammation. The implication of cardiovascular drug consumption in aetiopathogenesis of OA should be considered when prescribing ion channel modulators, particularly in long-term therapy protocols.
Investigation of Neurodevelopmental Deficits of 22 q11.2 Deletion Syndrome with a Patient-iPSC-Derived Blood–Brain Barrier Model
Authors: Li Yunfei , Xia Yifan , Zhu Huixiang , Luu Eric , Huang Guangyao , Sun Yan , Sun Kevin , Markx Sander , Leong Kam W. , Xu Bin , Fu Bingmei M.
Published: September 2021

The blood–brain barrier (BBB) is important in the normal functioning of the central nervous system. An altered BBB has been described in various neuropsychiatric disorders, including schizophrenia. However, the cellular and molecular mechanisms of such alterations remain unclear. Here, we investigate if BBB integrity is compromised in 22q11.2 deletion syndrome (also called DiGeorge syndrome), which is one of the validated genetic risk factors for schizophrenia. We utilized a set of human brain microvascular endothelial cells (HBMECs) derived from the induced pluripotent stem cell (iPSC) lines of patients with 22q11.2-deletion-syndrome-associated schizophrenia. We found that the solute permeability of the BBB formed from patient HBMECs increases by ~1.3–1.4-fold, while the trans-endothelial electrical resistance decreases to ~62% of the control values. Correspondingly, tight junction proteins and the endothelial glycocalyx that determine the integrity of the BBB are significantly disrupted. A transcriptome study also suggests that the transcriptional network related to the cell–cell junctions in the compromised BBB is substantially altered. An enrichment analysis further suggests that the genes within the altered gene expression network also contribute to neurodevelopmental disorders. Our findings suggest that neurovascular coupling can be targeted in developing novel therapeutical strategies for the treatment of 22q11.2 deletion syndrome.
NanoHIV: A Bioinformatics Pipeline for Producing Accurate, Near Full-Length HIV Proviral Genomes Sequenced Using the Oxford Nanopore Technology
Authors: Wright Imogen A. , Delaney Kayla E. , Katusiime Mary Grace K. , Botha Johannes C. , Engelbrecht Susan , Kearney Mary F. , van Zyl Gert U.
Published: September 2021

HIV-1 proviral single-genome sequencing by limiting-dilution polymerase chain reaction (PCR) amplification is important for differentiating the sequence-intact from defective proviruses that persist during antiretroviral therapy (ART). Intact proviruses may rebound if ART is interrupted and are the barrier to an HIV cure. Oxford Nanopore Technologies (ONT) sequencing offers a promising, cost-effective approach to the sequencing of long amplicons such as near full-length HIV-1 proviruses, but the high diversity of HIV-1 and the ONT sequencing error render analysis of the generated data difficult. NanoHIV is a new tool that uses an iterative consensus generation approach to construct accurate, near full-length HIV-1 proviral single-genome sequences from ONT data. To validate the approach, single-genome sequences generated using NanoHIV consensus building were compared to Illumina® consensus building of the same nine single-genome near full-length amplicons and an average agreement of 99.4% was found between the two sequencing approaches.
Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers
Authors: Lin Chia-Ni , Shiao Ming-Shi , Cheng Mei-Ling , Chen Chiung-Mei , Kuo Hung-Chou
Published: September 2021

This study aims to present the serum metabolite profiles of patients with acute intermittent porphyria (AIP) and identify specific metabolites that could potentially discriminate between AIP, asymptomatic HMBS mutation carriers, and healthy individuals. The study cohort included 46 female participants: 21 AIP patients, 5 asymptomatic carriers, and 20 ‘normal’ participants (without HMBS gene mutation). Serum samples were analyzed for 157 selected metabolites or clinical variables using an assay combining liquid chromatography MS/MS and direct flow injection. AUC analysis was used to distinguish unique variables between the three groups. A total of 15 variables differed significantly between the AIP and normal control group (VIP score > 1.0 and p < 0.05 with FDR correction). In AIP patients, the levels tyrosine, valine, and eGFR were significantly lower, and the levels of sphingomyelin C16:0, C24:0, C24:1, phosphatidylcholine diacyl C32:1, C36:1, C36:3, ornithine, sarcosine, citrulline, blood urea nitrogen AST, and ALT were significantly higher. The AUC of these 15 variables in discriminating between normal and AIP patients ranged between 0.73 and 0.94 (p < 0.05). In conclusion, serum metabolic profiles differ between normal individuals and patients carrying the HMBS mutation. The unique metabolites associated with AIP identified in this study may be useful for monitoring the development of AIP symptoms.
Experiences of Opening Up Communicative Spaces for Large-Scope Issues
Authors: Kalliola Satu , Heiskanen Tuula
Published: September 2021

The continuously changing world creates new challenges, large-scope issues, both at the community and the organizational level. Currently, sustainable development is among the key issues demanding organizational learning and new ways of operation. The paper looks for the potential of Scandinavian communicative-oriented action research (AR), applied in dialogue forums, to enhance learning and planning of integrative solutions to meet the needs of various actor groups. The paper links two intertwined AR lines of a Finnish work research institute to the contexts of classic and current AR discussion and their original social conditions in the early 1990s, when they were challenged by a severe recession. The characteristics of communicative spaces applied in the two cases are analysed qualitatively. The data, consisting of case reports, are reread and interpreted in a framework that concretizes Habermasian ideals of free communication. The elements of organisational learning and power embedded in the organisational positions of the participants dealing with large-scope societal issues are made explicit. Free communication and joint agreements of concrete plans require active agency that can be learned in a psychologically and socially safe communicative space where Habermasian lifeworld and system interact. The research shows the malleability of dialogue-based communicative spaces that can be applied in versatile social and organizational conditions. A future option would be a continuous dialogue applied in permanent dialogue structures.
Management of Infectious Lymphadenitis in Children
Authors: Pecora Francesco , Abate Luciana , Scavone Sara , Petrucci Irene , Costa Federico , Caminiti Caterina , Argentiero Alberto , Esposito Susanna
Published: September 2021

Lymphadenopathy is an irregularity in the size and texture of the lymph nodes, which is quite common in childhood. When the enlargement of lymph nodes is caused by inflammatory and infectious processes, it is called lymphadenitis. The main objective of this manuscript is to summarize the common infectious etiologies and presentations of lymphadenitis in children providing a management guide for clinical practice. PubMed was used to search for all of the studies published up to April 2021 using keywords such as “lymphadenitis” and “children”. Literature analysis showed that the differential diagnosis for lymphadenitis in pediatrics is broad. Although lymph node enlargement in children is usually benign and self-limited, it is important to exclude malignant etiology. In most cases, history and physical examination allow to identify the correct diagnosis and start a proper treatment with a prompt resolution of the lymphadenopathy. However, particularly in the case of persistent lymphadenitis, determining the cause of lymph node enlargement may be difficult, and the exact etiology may not be identified despite extensive investigations. Further studies should develop and validate an algorithm to assist pediatricians in the diagnosis and timely treatment of lymphadenitis, suggesting situations in which a watchful waiting may be considered a safe approach, those in which empiric antibiotic therapy should be administered, and those requiring a timely diagnostic work-up.
Human Milk, More Than Simple Nourishment
Authors: Vizzari Giulia , Morniroli Daniela , Ceroni Federica , Verduci Elvira , Consales Alessandra , Colombo Lorenzo , Cerasani Jacopo , Mosca Fabio , Giannì Maria Lorella
Published: September 2021

Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant’s neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.
Characterization of MAO + Cu Composite Coatings on Aluminum Alloy
Authors: Wu Shang-Kun , Yang Wei , Gao Wei , Yao Yu-Hong , Zhang Yong , Chen Jian
Published: September 2021

Novel composite coatings were fabricated on 6061 aluminum alloy substrates by two steps combining micro-arc oxidation (MAO) plus electroless copper plating (Cu). Different MAO + Cu composite coatings were compared. Cu continuously and evenly covered an aluminum oxide surface during processing thus changing the surface topography. The adhesion of MAO + Cu composite coating was tested by the pull-out method. The best adhesion strength of the composite coating can reach industrial requirements. The effects of the composite coatings on friction were investigated using a ball-on-disc test method. It is found that copper in composite coatings plays a lubricating effect during the wear process under dry sliding. Furthermore, the mechanisms by which the observed advantages were produced are discussed.
Improved Adhesion and Tribological Properties of AlTiN-TiSiN Coatings Deposited by DCMS and HiPIMS on Nitrided Tool Steels
Authors: Claver Adrián , Randulfe Jesús J. , Palacio José F. , Fernández de Ara Jonathan , Almandoz Eluxka , Montalá Francesc , Colominas Carles , Cot Victor , García Jose A.
Published: September 2021

Hard coatings, such as AlTiN-TiSiN, deposited by Physical Vapor Deposition (PVD) techniques are widely used in industrial applications to protect and increase the lifetime of industrial components, such as cutting tools, dies, and forming tools. Despite their great properties, such as high hardness and wear and oxidation resistance, they are limited in cases of severe conditions due to the poor adhesion between the coating and the substrate. Duplex treatments have commonly been used to improve the adhesive properties of PVD coatings, especially those of the cathodic arc evaporation type. The purpose of this study is to achieve coatings with the good properties of the Magnetron Sputtering processes but with higher adhesion than that achieved with these techniques, thus achieving coatings that can be used under the most severe conditions. In this work, an AlTiN-TiSiN coating was deposited by a combination of DC Magnetron Sputtering (DCMS) and High-Power Impulse Magnetron Sputtering (HiPIMS) after a gas nitriding pretreatment on 1.2379 and Vanadis 4 tool steels. Mechanical (ultra-microhardness and scratch tests) and tribological tests were carried out to study the improvement in the properties of the coating. Duplex-treated samples showed improved adhesion between the coating and the substrate, with second critical load (Lc2) values greater than 100 N. Furthermore, they showed great toughness and wear resistance. These results show that this type of coating technique could be used in the most extreme applications and that they can compete with other techniques and coatings that to date they have not been able to compete with.
Correction: Jain et al. An In-Vitro Study to Evaluate the Effect of Denture Cleansing Agents on Color Stability of Denture Bases Fabricated Using CAD/CAM Milling, 3D-Printing and Conventional Techniques. Coatings 2021, 11, 962
Authors: Jain Saurabh , Sayed Mohammed , Ahmed Walaa Magdy , Halawi Amjad Hussain Asiri , Najmi Naif Mohammed Ahmed , Aggarwal Aparna , Bhandi Shilpa , Patil Shankargouda
Published: September 2021

The authors have found three typing errors in their published paper and would like to make corrections in this paper [...]
Pavement Friction Prediction Using 3D Texture Parameters
Authors: Kováč Matúš , Brna Matej , Decký Martin
Published: September 2021

This article deals with the possibility of predicting skid resistance based on non-contact scanning of the road surface. The study is based on comparing pavement texture parameters with coefficients of friction measured on a wide variety of road surfaces, while other test conditions were the same and constant. The measurements of the coefficient of friction were performed using a pendulum tester. The pavement texture was measured using a static road scanner, and 85 different 3D texture parameters were calculated. The study shows that the determination of the friction using only single texture parameters is not sufficient. Based on this statement, the next part of the research analyzed the influence of the mutual combination of surface texture parameters. A linear regression model was chosen to determine the friction coefficient prediction formula based on the combination of texture parameters. Statistically, the most significant parameters in the prediction model proved to be the valley material portion, characterizing the microtexture, and the arithmetic mean curvature, characterizing the pavement macrotexture. The obtained regression model proved to be statistically significant with R2 = 0.81 for Pendulum Test Value prediction.
Hybrid Graphene-Based Photonic-Plasmonic Biochemical Sensor with a Photonic and Acoustic Cavity Structure
Authors: Yang Chan-Shan , Cheng Yi-Sheng , Hsu Young-Chou , Chung Yi-Cheng , Hung Jing-Ting , Liu Chien-Hao , Hsu Jin-Chen , Chen Cheng-Ying , Yang Chii-Rong , Li Yu-Tai , Huang Nan-Nong , Lin Tzy-Rong
Published: September 2021

In this study, we propose a biochemical sensor that features a photonic cavity integrated with graphene. The tunable hybrid plasmonic-photonic sensor can detect the molecular fingerprints of biochemicals with a small sample volume. The stacking sequence of the device is “ITO grating/graphene/TiO2/Au/Si substrate”, which composes a photonic band gap structure. A defect is created within the ITO gratings to form a resonant cavity. The plasmonic-photonic energy can be confined in the cavity to enhance the interaction between light and the analyte deposited in the cavity. The finite element simulation results indicated that the current sensor exhibits very high values in resonance shift and sensitivity. Moreover, the resonance spectrum with a broad resonance linewidth can identify the molecular vibration bands, which was exemplified by the fingerprint detections of protein and the chemical compound CBP. The sensor possesses an electrical tunability by including a graphene layer, which allowed us to tune the effective refractive index of the cavity to increase the sensor’s sensing performance. In addition, our device admits a phononic bandgap as well, which was exploited to sense the mechanical properties of two particular dried proteins based on the simplified elastic material model instead of using the more realistic viscoelastic model. The dual examinations of the optical and mechanical properties of analytes from a phoxonic sensor can improve the selectivity in analyte detections.
The Surgical Management of Proximal Femoral Metastases: A Narrative Review
Authors: Axelrod Daniel , Gazendam Aaron M. , Ghert Michelle
Published: September 2021

The proximal femur is a common location for the development of bony metastatic disease. Metastatic bone disease in this location can cause debilitating pain, pathologic fractures, reduced quality of life, anemia or hypercalcemia. A thorough history, physical examination and preoperative investigations are required to ensure accurate diagnosis and prognosis. The goals of surgical management is to provide pain relief and return to function with a construct that provides stability to allow for immediate weightbearing. Current surgical treatment options include intramedullary nailing, hemiarthroplasty or total hip arthroplasty and endoprosthetic reconstructions. Oligometastatic renal cell carcinoma must be given special consideration as tumor resection and reconstruction has survival benefit. Both tumor and patient characteristics must be taken into account before deciding on the appropriate surgical intervention.
Assessment of Risk of Bias in Osteosarcoma and Ewing’s Sarcoma Randomized Controlled Trials: A Systematic Review
Authors: Koucheki Robert , Gazendam Aaron M. , Perera Jonathan R. , Griffin Anthony , Ferguson Peter , Wunder Jay , Tsoi Kim
Published: September 2021

Aim: The aim of this study was to systematically assess the risk of bias in osteosarcoma and Ewing’s sarcoma (ES) randomized controlled trials (RCT) and to examine the relationships between bias and conflict of interest/industry sponsorship. Methods: An OVID-MEDLINE search was performed (1976–2019). Using the Cochrane Collaboration guidelines, two reviewers independently assessed the prevalence of risk of bias in different RCT design domains. The relationship between conflicts of interest and industry funding with the frequency of bias was examined. Results: 73 RCTs met inclusion criteria. Prevalence of low-risk bias domains was 47.3%, unclear-risk domains 47.8%, and 4.9% of the domains had a high-risk of bias. Domains with the highest risk of bias were blinding of participants/personnel and outcome assessors, followed by randomization and allocation concealment. Overtime, frequency of unclear-risk of bias domains decreased (χ2 = 5.32, p = 0.02), whilst low and high-risk domains increased (χ2 = 8.13, p = 0.004). Studies with conflicts of interest and industry sponsorships were 4.2 and 3.1 times more likely to have design domains with a high-risk of bias (p < 0.05). Conclusion: This study demonstrates that sources of potential bias are prevalent in both osteosarcoma and ES RCTs. Studies with financial conflicts of interest and industry sponsors were significantly more likely to have domains with a high-risk of bias. Improvements in reporting and adherence to proper methodology will reduce the risk of bias and improve the validity of the results of RCTs in osteosarcoma and ES.
Feasibility of Stereotactic Body Radiation Therapy on Unresectable Stage III NSCLC with Peripheral Primary Tumor: A Prospective Study (GFPC 01-14)
Authors: Martel-Lafay Isabelle , Monnet Isabelle , Lardy-Cleaud Audrey , Danhier Serge , Salem Naji , Gallocher Olivier , Fournel Pierre , Chouaid Christos , Bylicki Olivier ,   the GFPC 01-14 Investigators
Published: September 2021

Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase II trial in unresectable stage III NSCLC with peripheral primary tumor evaluated the feasibility of stereotactic body radiation therapy (SBRT) in peripheral tumor after concomitant radio-chemotherapy (RT-CT). Nineteen patients were included and analyzed (median age, 60.9 years; male, 78%; adenocarcinoma, 74%; median size of peripheral primary tumor, 19 mm). At 6 months, the disease control rate was 79% (15/19). SBRT toxicity was generally mild with one (5%) patient having grade 3 lung toxicity. Recruitment for this study was stopped prior to completion, firstly due to the approval of adjuvant durvalumab after RT-CT, which was not anticipated in the design, and secondly due to the small number of stage III NSCLC patients with a peripheral tumor that was accessible to SBRT. Nevertheless, the combination of RT-CT and SBRT appeared to be feasible and safe.
Fusarium casha sp. nov. and F. curculicola sp. nov. in the Fusarium fujikuroi Species Complex Isolated from Amaranthuscruentus and Three Weevil Species in South Africa
Authors: Vermeulen Marcele , Rothmann Lisa A. , Swart Wijnand J. , Gryzenhout Marieka
Published: September 2021

Trials are currently being conducted in South Africa to establish Amaranthus cruentus as a new pseudocereal crop. During recent surveys, Fusarium species were associated with weevil damage in A. cruentus fields. Preliminary studies showed that some of these Fusarium species grouped into two distinct clades within the F. fujikuroi species complex. The aim of this study was to characterize these isolates based on the morphology and phylogeny of the translation elongation factor 1α (TEF1α) gene region, ß-tubulin 2 (ßT) gene region and RNA polymerase II subunit (RPB2), and to determine if these isolates are pathogenic to A. cruentus. Phylogenetic and morphological studies showed that these two clades represent two novel species described here as F. casha and F. curculicola. Both species were shown to have the potential to be pathogenic to A. cruentus during routine greenhouse inoculation tests. While isolations indicate a possible association between these two species and weevils, further research is needed to understand this association and the role of weevils in disease development involving F. casha and F. curculicola in A. cruentus.
FMRP Levels in Human Peripheral Blood Leukocytes Correlates with Intellectual Disability
Authors: Roth Mark , Ronco Lucienne , Cadavid Diego , Durbin-Johnson Blythe , Hagerman Randi J. , Tassone Flora
Published: September 2021

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is an X-linked, neurodevelopmental disorder caused by a CGG trinucleotide repeat expansion in the 5′ untranslated region (UTR) of the Fragile X Mental Retardation gene, FMR1. Greater than 200 CGG repeats results in epigenetic silencing of the gene leading to the deficiency or absence of Fragile X mental retardation protein (FMRP). The loss of FMRP is considered the root cause of FXS. The relationship between neurological function and FMRP expression in peripheral blood mononuclear cells (PBMCs) has not been well established. Assays to detect and measure FMR1 and FMRP have been described; however, none are sufficiently sensitive, precise, or quantitative to properly characterize the relationships between cognitive ability and CGG repeat number, FMR1 mRNA expression, or FMRP expression measured in PBMCs. To address these limitations, two novel immunoassays were developed and optimized, an electro-chemiluminescence immunoassay and a multiparameter flow cytometry assay. Both assays were performed on PMBCs isolated from 27 study participants with FMR1 CGG repeats ranging from normal to full mutation. After correcting for methylation, a significant positive correlation between CGG repeat number and FMR1 mRNA expression levels and a significant negative correlation between FMRP levels and CGG repeat expansion was observed. Importantly, a high positive correlation was observed between intellectual quotient (IQ) and FMRP expression measured in PBMCs.
The Comparison and Interpretation of Machine-Learning Models in Post-Stroke Functional Outcome Prediction
Authors: Chang Shih-Chieh , Chu Chan-Lin , Chen Chih-Kuang , Chang Hsiang-Ning , Wong Alice M. K. , Chen Yueh-Peng , Pei Yu-Cheng
Published: September 2021

Prediction of post-stroke functional outcomes is crucial for allocating medical resources. In this study, a total of 577 patients were enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) program, and 77 predictors were collected at admission. The outcome was whether a patient could achieve a Barthel Index (BI) score of >60 upon discharge. Eight machine-learning (ML) methods were applied, and their results were integrated by stacking method. The area under the curve (AUC) of the eight ML models ranged from 0.83 to 0.887, with random forest, stacking, logistic regression, and support vector machine demonstrating superior performance. The feature importance analysis indicated that the initial Berg Balance Test (BBS-I), initial BI (BI-I), and initial Concise Chinese Aphasia Test (CCAT-I) were the top three predictors of BI scores at discharge. The partial dependence plot (PDP) and individual conditional expectation (ICE) plot indicated that the predictors’ ability to predict outcomes was the most pronounced within a specific value range (e.g., BBS-I < 40 and BI-I < 60). BI at discharge could be predicted by information collected at admission with the aid of various ML models, and the PDP and ICE plots indicated that the predictors could predict outcomes at a certain value range.
Metabolomic Profiles of Men and Women Ischemic Stroke Patients
Authors: Poupore Nicolas , Chosed Renee , Arce Sergio , Rainer Robert , Goodwin Richard L. , Nathaniel Thomas I.
Published: September 2021

Background: Stroke is known to affect both men and women; however, incidence and outcomes differ between them. Therefore, the discovery of novel, sex-specific, blood-based biomarkers for acute ischemic stroke (AIS) patients has the potential to enhance the understanding of the etiology of this deadly disease in the content of sex. The objective of this study was to identify serum metabolites associated with male and female AIS patients. Methods: Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography-tandem mass spectrometry quantification from blood specimens collected from AIS patients. Samples were collected from 36 patients comprising each of 18 men and women with matched controls. Metabolic pathway analysis and principal component analysis (PCA) was used to differentiate metabolite profiles for male and female AIS patients from the control, while logistic regression was used to determine differences in metabolites between male and female AIS patients. Results: In female AIS patients, 14 distinct altered metabolic pathways and 49 corresponding metabolites were identified, while 39 metabolites and 5 metabolic pathways were identified in male patients. Metabolites that are predictive of ischemic stroke in female patients were 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4) (AUC = 0.914, 0.765–1.000), 1-(1-enyl-palmitoyl)-2-palmitoyl-GPC (P-16:0/16:0) (AUC = 0.840, 0.656–1.000), and 5,6-dihydrouracil (P-16:0/20:2) (AUC = 0.815, 0.601–1.000). Significant metabolites that were predictive of stroke in male patients were 5alpha-androstan-3alpha,17beta-diol disulfate (AUC = 0.951, 0.857–1.000), alpha-hydroxyisocaproate (AUC = 0.938, 0.832–1.000), threonate (AUC = 0.877, 0.716–1.000), and bilirubin (AUC = 0.817, 0.746–1.000). Conclusions: In the current study, the untargeted serum metabolomics platform identified multiple pathways and metabolites associated with male and female AIS patients. Further research is necessary to characterize how these metabolites are associated with the pathophysiology in male and female AIS patients.
Capsule Endoscopy for Gastric Evaluation
Authors: Kim Ji-Hyun , Nam Seung-Joo
Published: September 2021

Wireless capsule endoscopy was first developed to observe the small intestine. A small capsule can be swallowed and images of gastrointestinal tract are taken with natural movement of peristalsis. Application of capsule endoscopy for observing the stomach has also received much attention as a useful alternative to esophagogastroduodenoscopy, but anatomical characteristics of the stomach have demanded technical obstacles that need to be tackled: clear visualization and active movements that could be controlled. Different methods of controlling the capsule within stomach have been studied and magnetic manipulation is the only system that is currently used in clinical settings. Magnets within the capsule can be controlled with a hand-held magnet paddle, robotic arm, and electromagnetic coil system. Studies on healthy volunteers and patients with upper gastrointestinal symptoms have shown that it is a safe and effective alternative method of observing the stomach. This work reviews different magnetic locomotion systems that have been used for observation of the stomach as an emerging new application of wireless capsule endoscopy.
Multiple Chromatographic Analysis of Urine in the Detection of Bladder Cancer
Authors: Džubinská Daniela , Zvarík Milan , Kollárik Boris , Šikurová Libuša
Published: September 2021

Bladder cancer (BC) is the most common type of carcinoma of the urological system. Recently, there has been an increasing interest in non-invasive diagnostic tumor markers due to the invasive attribute of cystoscopy, which is still considered the gold standard diagnostic method. However, markers published in the literature so far do not meet expectations for replacing cystoscopy due to their low specificity and excessively high false-positive results, which can be mainly caused by frequently occurring hematuria also in benign cases. No reliable non-invasive method has yet been identified that can distinguish patients with bladder cancer and non-malignant hematuria patients. Our work examined the possibilities of non-targeted biomarkers of urine to distinguish patients with malignant and non-malignant diseases of the bladder using 3D HPLC in combination with computer processing of multiple datasets. Urine samples from 47 patients, 23 patients with bladder cancer (BC) and 24 patients with non-malignant hematuria (NMHU), were enrolled in clinical trials. For the separation and subsequent analysis of a large number of urine components, 3D HPLC (high-performance liquid chromatography) with an absorption and fluorescence detector was used. The obtained dataset was further subjected to various uni- and multi-dimensional statistical analyses and mathematical modeling. We found 334 chromatographic peaks, of which 18 peaks were identified as significantly different for BC and NMHU patients. Using receiver operating characteristic (ROC) analysis, we assessed the informative ability of significant chromatographic peaks (90% sensitivity and 74% specificity). By logistic regression, we identified the optimal and simplified set of seven chromatographic peaks (5 absorptions plus 2 fluorescence) with strong classification power (100% sensitivity and 100% specificity) for distinguishing patients with bladder cancer and those with non-malignant hematuria. Partial least square discriminant analysis (PLS-DA) model and orthogonal projection to latent structure discriminant analysis (OPLS-DA) with 100% sensitivity and 96% specificity were used to distinguish BC and NMHU patients. Multivariate statistical analysis of urinary metabolomic profiles of patients revealed that BC patients can be discriminated from NMHU patients and the results can likely contribute to an early and non-invasive diagnosis of BC.
Empowering Melatonin Therapeutics with Drosophila Models
Authors: Millet-Boureima Cassandra , Ennis Caroline C. , Jamison Jurnee , McSweeney Shana , Park Anna , Gamberi Chiara
Published: September 2021

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.
An Extended Entropic Model for Cohesive Sediment Flocculation in a Piecewise Varied Shear Environment
Authors: Zhu Zhongfan , Dou Jie
Published: September 2021

In this study, an extended model for describing the temporal evolution of a characteristic floc size of cohesive sediment particles when the flocculation system is subject to a piecewise varied turbulent shear rate was derived by the probability methods based on the Shannon entropy theory following Zhu (2018). This model only contained three important parameters: initial and steady-state values of floc size, and a parameter characterizing the maximum capacity for floc size increase (or decay), and it can be adopted to capture well a monotonic pattern in which floc size increases (or decays) with flocculation time. Comparison with 13 literature experimental data sets regarding floc size variation to a varied shear rate showed the validity of the entropic model with a high correlation coefficient and few errors. Furthermore, for the case of tapered shear flocculation, it was found that there was a power decay of the capacity parameter with the shear rate, which is similar to the dependence of the steady-state floc size on the shear rate. The entropic model was further parameterized by introducing these two empirical relations into it, and the finally obtained model was found to be more sensitive to two empirical coefficients that have been incorporated into the capacity parameter than those in the steady-state floc size. The proposed entropic model could have the potential, as an addition to existing flocculation models, to be coupled into present mature hydrodynamic models to model the cohesive sediment transport in estuarine and coastal regions.
How Financial Performance and State-Owned Enterprise (SOE) Values Are Affected by Good Corporate Governance and Intellectual Capital Perspectives
Authors: Hermanto Yustinus Budi , Lusy Lusy , Widyastuti Maria
Published: September 2021

The implementation of good governance and attention to resources will affect company survival. The purpose of this study was to examine the effect of good corporate governance and intellectual capital on financial performance and company value through statistical and econometrical tests on SOEs in Indonesia. This is quantitative research with state-owned enterprises (SOEs) listed on the Indonesia Stock Exchange. The total study population was 16 SOEs. This study used a saturated sample. Furthermore, the exogenous variables in this study were good corporate governance (GCG) and intellectual capital, whereas the endogenous variables were the company and financial performance. This study used the statistical analysis inferential because the variables used indicators and were formative. The results indicated that GCG and financial performance have positive effects on firm value, intellectual capital does not affect company value, and GCG and intellectual capital have positive effects on financial performance. The evaluation of indirect effects in this study showed that financial performance mediates the effect of intellectual capital and GCG on company value.
Psychological Factors Explaining Perceived Impact of COVID-19 on Travel
Authors: Magano José , Vidal Diogo Guedes , Sousa Hélder Fernando Pedrosa e , Dinis Maria Alzira Pimenta , Leite Ângela
Published: September 2021

This cross-sectional study aims to determine the psychological factors that contribute to the perceived impact of COVID-19 on travel using a convenience sample (N = 1122) from the general population to whom instruments assessing the perception of the COVID-19 pandemic’s impact on travel, anxiety, fear, phobia, risk perception, and stress were applied. The participants were mainly female (65.6%), had not attended university, and who were professionally active, with a mean age of around 30-years-old (M = 31.91, SD = 13.76, Min = 18, Max = 81). The perceived impact of COVID-19 on travel correlates with all of the psychological variables, mainly in terms of the emotional fear of COVID-19. Together with the perceived risk of COVID-19, social phobia due to COVID-19, and COVID-19 stress contamination, these variables explain 20% of the perceived impact of COVID-19 on travel variance. The relationship between COVID-19 stress socio-economic consequences and the perception of the pandemic’s impact on travel is moderated by the emotional perceived risk of COVID-19. Fear and perception of this risk explain the impact of the COVID-19 on travel in pandemic times, suggesting that the psychological impact of fear and anxiety induced by the pandemic needs to be handled as a public health priority.