bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies
Authors: Pal Dilipkumar , Raj Khushboo , Nandi Shyam Sundar , Sinha Surajit , Mishra Abhishek , Mondal Arijit , Lagoa Ricardo , Burcher Jack T. , Bishayee Anupam
Published: May 2023

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor cells by the immune system, thereby diminishing tumor immunity. The argument for employing epigenetic drugs in the treatment of acute myeloid leukemia (AML) patients is supported by evidence that both epigenetic changes and mutations in the epigenetic machinery contribute to AML etiology. Although hypomethylating drugs have been licensed for use in AML, additional epigenetic inhibitors, such as HDACis, are now being tested in humans. Preclinical studies evaluating the efficacy of HDACis against AML have shown the ability of specific agents, such as anobinostat, vorinostat, and tricostatin A, to induce growth arrest, apoptosis, autophagy and cell death. However, these inhibitors do not seem to be successful as monotherapies, but instead achieve results when used in conjunction with other medications. In this article, we discuss the mounting evidence that HDACis promote extensive histone acetylation, as well as substantial increases in reactive oxygen species and DNA damage in hematological malignant cells. We also evaluate the potential of various natural product-based HDACis as therapeutic agents to combat hematological malignancies.
Risk Factors for Palbociclib-Induced Early Developing Neutropenia in Patients with Hormone Receptor-Positive Metastatic Breast Cancer
Authors: Lee Yeonhong , Lee Dayae , Seo Inyoung , Chae Heejung , Sim Sung Hoon , Lee Keun Seok , Gwak Hye Sun
Published: May 2023

Purpose: This study aimed to determine the risk factors for palbociclib-induced grade 4 or grade 3 neutropenia (NP) requiring dose reduction or delayed treatment in patients with HR+/HER2−metastatic breast cancer in the first 3 cycles (early grade 3/4 NP) and whether the early developing grade 3/4 NP affects progression-free survival. Methods: A retrospective study using electronic medical records was conducted on patients who received palbociclib for metastatic breast cancer between January 2018 and August 2022. The early grade 3/4 NP risk factors were evaluated with univariate and multivariable logistic regression analyses. In addition, the Kaplan-Meier method was used to estimate the median progression-free survival (PFS) to analyze the effect of early grade 3/4 NP on treatment. Results: Out of the 264 patients included in this study, 173 (65.6%) experienced early grade 3/4 NP. A total of four models were applied for multivariable analysis to identify early grade 3/4 NP-developing factors. Low baseline ANC, WBC, PLT, and BSA were significant risk factors for early grade 3/4 NP; baseline ANC < 3700/mm3, WBC < 6.30 × 109/mm3, PLT < 230 × 109/mm3, and BSA < 1.58 m2 increased the risk by approximately 4.0-fold, 3.7–4.0-fold, 2.1-fold, and 2.0-fold, respectively. Early grade 3/4 NP did not affect PFS (p = 0.710), although patients with early grade 3/4 NP had more frequent dose reductions or treatment delays. Conclusions: Based on the results, low baseline ANC, WBC, PLT, and BSA were associated with early grade 3/4 NP. Patients with risk factors require careful monitoring, and this study is expected to help predict NP, which may appear in early treatment.
Cross-Resistance between Platinum-Based Chemotherapy and PARP Inhibitors in Castration-Resistant Prostate Cancer
Authors: Slootbeek Peter H. J. , Kloots Iris S. H. , van Oort Inge M. , Kroeze Leonie I. , Schalken Jack A. , Bloemendal Haiko J. , Mehra Niven
Published: May 2023

Patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring homologous recombination repair-related gene aberrations (HRRm) can derive meaningful benefits from both platinum-based chemotherapy (PlCh) and PARP inhibitors (PARPi). Cross-resistance between these agents is well-recognised in other tumour types but data on prostate cancer is lacking. In this retrospective pre-planned study, we assessed 28 HRRm mCRPC patients who received PlCh and PARPi. Progression-free survival (PFS) on initial therapy was longer than on subsequent therapy (median 5.3 vs. 3.4 months, p = 0.016). The median PFS of PlCh was influenced by the order of agents, with 3.6 months shorter PFS after PARPi than when administered first. The median PFS of PARPi was less influenced, with 0.9 months shorter PFS after PlCh than before. In the PARPi-first subgroup, six out of 16 evaluable patients (37.5%) had a >50% PSA decline to PlCh, and two of eight (25.0%) had a radiographic response to PlCh. In the PlCh-first subgroup, 6/10 (60.0%) had a >50% PSA decline, and 5/9 (55.6%) had a radiographic response to PARPi. These data show >40% of the cohort is sensitive to a subsequent HRR-targeting agent. PlCh appears to induce less cross-resistance than PARPi. Additional data on resistance mechanisms will be crucial in defining an optimal treatment sequence in HRRm mCRPC patients.
Chemoradiotherapy for Head and Neck Cancer
Authors: D’Onofrio Ida , Nardone Valerio , Reginelli Alfonso , Cappabianca Salvatore
Published: May 2023

Head and neck squamous cell carcinoma (HNSCC) is a highly challenging cancer [...]
Genomic and Epigenetic Changes Drive Aberrant Skeletal Muscle Differentiation in Rhabdomyosarcoma
Authors: Pomella Silvia , Danielli Sara G. , Alaggio Rita , Breunis Willemijn B. , Hamed Ebrahem , Selfe Joanna , Wachtel Marco , Walters Zoe S. , Schäfer Beat W. , Rota Rossella , Shipley Janet M. , Hettmer Simone
Published: May 2023

Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children and adolescents, represents an aberrant form of skeletal muscle differentiation. Both skeletal muscle development, as well as regeneration of adult skeletal muscle are governed by members of the myogenic family of regulatory transcription factors (MRFs), which are deployed in a highly controlled, multi-step, bidirectional process. Many aspects of this complex process are deregulated in RMS and contribute to tumorigenesis. Interconnected loops of super-enhancers, called core regulatory circuitries (CRCs), define aberrant muscle differentiation in RMS cells. The transcriptional regulation of MRF expression/activity takes a central role in the CRCs active in skeletal muscle and RMS. In PAX3::FOXO1 fusion-positive (PF+) RMS, CRCs maintain expression of the disease-driving fusion oncogene. Recent single-cell studies have revealed hierarchically organized subsets of cells within the RMS cell pool, which recapitulate developmental myogenesis and appear to drive malignancy. There is a large interest in exploiting the causes of aberrant muscle development in RMS to allow for terminal differentiation as a therapeutic strategy, for example, by interrupting MEK/ERK signaling or by interfering with the epigenetic machinery controlling CRCs. In this review, we provide an overview of the genetic and epigenetic framework of abnormal muscle differentiation in RMS, as it provides insights into fundamental mechanisms of RMS malignancy, its remarkable phenotypic diversity and, ultimately, opportunities for therapeutic intervention.
Effective Circulating Tumor Cell Isolation Using Epithelial and Mesenchymal Markers in Prostate and Pancreatic Cancer Patients
Authors: Cha Jiwon , Cho Hyungseok , Chung Jae-Seung , Park Joon Seong , Han Ki-Ho
Published: May 2023

Circulating tumor cells (CTCs) display antigenic heterogeneity between epithelial and mesenchymal phenotypes. However, most current CTC isolation methods rely on EpCAM (epithelial cell adhesion molecule) antibodies. This study introduces a more efficient CTC isolation technique utilizing both EpCAM and vimentin (mesenchymal cell marker) antibodies, alongside a lateral magnetophoretic microseparator. The effectiveness of this approach was assessed by isolating CTCs from prostate (n = 17) and pancreatic (n = 5) cancer patients using EpCAM alone, vimentin alone, and both antibodies together. Prostate cancer patients showed an average of 13.29, 11.13, and 27.95 CTCs/mL isolated using EpCAM alone, vimentin alone, and both antibodies, respectively. For pancreatic cancer patients, the averages were 1.50, 3.44, and 10.82 CTCs/mL with EpCAM alone, vimentin alone, and both antibodies, respectively. Combining antibodies more than doubled CTC isolation compared to single antibodies. Interestingly, EpCAM antibodies were more effective for localized prostate cancer, while vimentin antibodies excelled in metastatic prostate cancer isolation. Moreover, vimentin antibodies outperformed EpCAM antibodies for all pancreatic cancer patients. These results highlight that using both epithelial and mesenchymal antibodies with the lateral magnetophoretic microseparator significantly enhances CTC isolation efficiency, and that antibody choice may vary depending on cancer type and stage.
Characterization of Skeletal Muscle Biopsy and Derived Myoblasts in a Patient Carrying Arg14del Mutation in Phospholamban Gene
Authors: Zanotti Simona , Ripolone Michela , Napoli Laura , Velardo Daniele , Salani Sabrina , Ciscato Patrizia , Priori Silvia , Kukavica Deni , Mazzanti Andrea , Diamanti Luca , Vegezzi Elisa , Moggio Maurizio , Corti Stefania , Comi Giacomo , Sciacco Monica
Published: May 2023

Phospholamban is involved in the regulation of the activity and storage of calcium in cardiac muscle. Several mutations have been identified in the PLN gene causing cardiac disease associated with arrhythmogenic and dilated cardiomyopathy. The patho-mechanism underlying PLN mutations is not fully understood and a specific therapy is not yet available. PLN mutated patients have been deeply investigated in cardiac muscle, but very little is known about the effect of PLN mutations in skeletal muscle. In this study, we investigated both histological and functional features in skeletal muscle tissue and muscle-derived myoblasts from an Italian patient carrying the Arg14del mutation in PLN. The patient has a cardiac phenotype, but he also reported lower limb fatigability, cramps and fasciculations. The evaluation of a skeletal muscle biopsy showed histological, immunohistochemical and ultrastructural alterations. In particular, we detected an increase in the number of centronucleated fibers and a reduction in the fiber cross sectional area, an alteration in p62, LC3 and VCP proteins and the formation of perinuclear aggresomes. Furthermore, the patient’s myoblasts showed a greater propensity to form aggresomes, even more marked after proteasome inhibition compared with control cells. Further genetic and functional studies are necessary to understand whether a definition of PLN myopathy, or cardiomyopathy plus, can be introduced for selected cases with clinical evidence of skeletal muscle involvement. Including skeletal muscle examination in the diagnostic process of PLN-mutated patients can help clarify this issue.
Role of Coactivator Associated Arginine Methyltransferase 1 (CARM1) in the Regulation of the Biological Function of 1,25-Dihydroxyvitamin D3
Authors: Mady Leila J. , Zhong Yan , Dhawan Puneet , Christakos Sylvia
Published: May 2023

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D, activates the nuclear vitamin D receptor (VDR) to mediate the transcription of target genes involved in calcium homeostasis as well as in non-classical 1,25(OH)2D3 actions. In this study, CARM1, an arginine methyltransferase, was found to mediate coactivator synergy in the presence of GRIP1 (a primary coactivator) and to cooperate with G9a, a lysine methyltransferase, in 1,25(OH)2D3 induced transcription of Cyp24a1 (the gene involved in the metabolic inactivation of 1,25(OH)2D3). In mouse proximal renal tubule (MPCT) cells and in mouse kidney, chromatin immunoprecipitation analysis demonstrated that dimethylation of histone H3 at arginine 17, which is mediated by CARM1, occurs at Cyp24a1 vitamin D response elements in a 1,25(OH)2D3 dependent manner. Treatment with TBBD, an inhibitor of CARM1, repressed 1,25(OH)2D3 induced Cyp24a1 expression in MPCT cells, further suggesting that CARM1 is a significant coactivator of 1,25(OH)2D3 induction of renal Cyp24a1 expression. CARM1 was found to act as a repressor of second messenger-mediated induction of the transcription of CYP27B1 (involved in the synthesis of 1,25(OH)2D3), supporting the role of CARM1 as a dual function coregulator. Our findings indicate a key role for CARM1 in the regulation of the biological function of 1,25(OH)2D3.
Resistance to Gemcitabine in Pancreatic Cancer Is Connected to Methylglyoxal Stress and Heat Shock Response
Authors: Crake Rebekah , Gasmi Imène , Dehaye Jordan , Lardinois Fanny , Peiffer Raphaël , Maloujahmoum Naïma , Agirman Ferman , Koopmansch Benjamin , D’Haene Nicky , Azurmendi Senar Oier , Arsenijevic Tatjana , Lambert Frédéric , Peulen Olivier , Van Laethem Jean-Luc , Bellahcène Akeila
Published: May 2023

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is the first-line therapy for PDAC, but gemcitabine resistance is a major impediment to achieving satisfactory clinical outcomes. This study investigated whether methylglyoxal (MG), an oncometabolite spontaneously formed as a by-product of glycolysis, notably favors PDAC resistance to gemcitabine. We observed that human PDAC tumors expressing elevated levels of glycolytic enzymes together with high levels of glyoxalase 1 (GLO1), the major MG-detoxifying enzyme, present with a poor prognosis. Next, we showed that glycolysis and subsequent MG stress are triggered in PDAC cells rendered resistant to gemcitabine when compared with parental cells. In fact, acquired resistance, following short and long-term gemcitabine challenges, correlated with the upregulation of GLUT1, LDHA, GLO1, and the accumulation of MG protein adducts. We showed that MG-mediated activation of heat shock response is, at least in part, the molecular mechanism underlying survival in gemcitabine-treated PDAC cells. This novel adverse effect of gemcitabine, i.e., induction of MG stress and HSR activation, is efficiently reversed using potent MG scavengers such as metformin and aminoguanidine. We propose that the MG blockade could be exploited to resensitize resistant PDAC tumors and to improve patient outcomes using gemcitabine therapy.
Current Strategies for Exosome Cargo Loading and Targeting Delivery
Authors: Zeng Haifeng , Guo Shaoshen , Ren Xuancheng , Wu Zhenkun , Liu Shuwen , Yao Xingang
Published: May 2023

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes.
Organotypic Hippocampal Slice Cultures from Adult Tauopathy Mice and Theragnostic Evaluation of Nanomaterial Phospho-TAU Antibody-Conjugates
Authors: Kemppainen Susanna , Huber Nadine , Willman Roosa-Maria , Zamora Ana , Mäkinen Petra , Martiskainen Henna , Takalo Mari , Haapasalo Annakaisa , Sobrino Tomás , González Gómez Manuel Antonio , Piñeiro Yolanda , Rivas José , Himmelreich Uwe , Hiltunen Mikko
Published: May 2023

Organotypic slice culture models surpass conventional in vitro methods in many aspects. They retain all tissue-resident cell types and tissue hierarchy. For studying multifactorial neurodegenerative diseases such as tauopathies, it is crucial to maintain cellular crosstalk in an accessible model system. Organotypic slice cultures from postnatal tissue are an established research tool, but adult tissue-originating systems are missing, yet necessary, as young tissue-originating systems cannot fully model adult or senescent brains. To establish an adult-originating slice culture system for tauopathy studies, we made hippocampal slice cultures from transgenic 5-month-old hTau.P301S mice. In addition to the comprehensive characterization, we set out to test a novel antibody for hyperphosphorylated TAU (pTAU, B6), with and without a nanomaterial conjugate. Adult hippocampal slices retained intact hippocampal layers, astrocytes, and functional microglia during culturing. The P301S-slice neurons expressed pTAU throughout the granular cell layer and secreted pTAU to the culture medium, whereas the wildtype slices did not. Additionally, cytotoxicity and inflammation-related determinants were increased in the P301S slices. Using fluorescence microscopy, we showed target engagement of the B6 antibody to pTAU-expressing neurons and a subtle but consistent decrease in intracellular pTAU with the B6 treatment. Collectively, this tauopathy slice culture model enables measuring the extracellular and intracellular effects of different mechanistic or therapeutic manipulations on TAU pathology in adult tissue without the hindrance of the blood–brain barrier.
Acute and Chronic Ethanol Effects during Adolescence on Neuroimmune Responses: Consequences and Potential Pharmacologic Interventions
Authors: Nwachukwu Kala N. , Mohammed Hassan E. , Mebane DaQuan R. , Barber Andrew W. , Swartzwelder H. Scott , Marshall S. Alex
Published: May 2023

Heavy ethanol consumption during adolescence has been linked to neuroimmune response dysregulation and cognitive deficits in the developing adolescent brain. During adolescence, the brain is particularly susceptible to the pharmacological effects of ethanol that are induced by acute and chronic bouts of exposure. Numerous preclinical rodent model studies have used different ethanol administration techniques, such as intragastric gavage, self-administration, vapor, intraperitoneal, and free access, and while most models indicated proinflammatory neuroimmune responses in the adolescent brain, there are various factors that appear to influence this observation. This review synthesizes the most recent findings of the effects of adolescent alcohol use on toll-like receptors, cytokines, and chemokines, as well as the activation of astrocytes and microglia with an emphasis on differences associated with the duration of ethanol exposure (acute vs. chronic), the amount of exposure (e.g., dose or blood ethanol concentrations), sex differences, and the timing of the neuroimmune observation (immediate vs. persistent). Finally, this review discusses new therapeutics and interventions that may ameliorate the dysregulation of neuroimmune maladaptations after ethanol exposure.
Hafnium-Zirconium Carbonitride (Hf,Zr)(C,N) by One Step Mechanically Induced Self-Sustaining Reaction: Powder Synthesis and Spark Plasma Sintering
Authors: Khadyrova Irina , Suvorova Veronika , Nepapushev Andrey , Suvorov Dmitrii , Kuskov Kirill , Moskovskikh Dmitry
Published: May 2023

Nanostructured single-phase hafnium-zirconium carbonitride powders were synthesized using a simple and fast mechanochemical synthesis approach. The critical milling duration, after which a (Hf,Zr)(C,N) solid solution formation inside a jar occurred via mechanically induced self-sustained reaction (MSR), was 10 min. After 30 min of treatment, a solid-gas reaction was completed, and as a result, a homogeneous (Hf,Zr)(C,N) powder consisting of 10–500 nm submicron particles was obtained. The phase and structure evolution of the powders after different treatment durations allowed for the establishment of possible reaction mechanisms, which included the formation of Hf/Zr/C-layered composite particles, their interaction via MSR, and further grinding and nitridization. Spark plasma sintering (SPS) was used to produce bulk hafnium-zirconium carbonitride ceramics from nanostructured powder. The sample had higher values of relative density, hardness, and fracture toughness than those for binary compounds of a similar composition.
Obtaining Foamed Glass-Ceramics from Diamond Concentration Tailings
Authors: Suvorova Olga V. , Manakova Nadezhda K. , Novikov Andrey I. , Makarov Dmitriy V.
Published: May 2023

The possibility of obtaining building foamed glass-ceramic using the diamond concentration tailings of the Lomonosov deposit in Arkhangelsk Region, Russia, is demonstrated here. The effect of the tailings’ particle size distribution, feed temperature, the addition of a foaming agent, and the content of oxidizer on the feed charge foaming is established. The process conditions for obtaining foamed glass-ceramic materials are described. The specifications of the materials with the optimal composition (tailings 50 wt.%, glass waste 50 wt.%, SiC 0.5 wt.%, Fe2O3 1 wt.%) foamed at 1020–1050 °C were as follows: apparent density 0.23–0.51 g/cm3, compression strength 0.58–2.40 MPa, water absorption (by volume) 8.7–19.0%. Based on the combination of the measured properties when used in dry conditions, the obtained materials can be considered heat-insulating foam materials. The thermal conductivity was 0.060–0.066 W/m·K.
Bitcoin Is Full of Surprises
Authors: Rudd Murray A.
Published: May 2023

Bitcoin has been embraced by many individuals with strong right-leaning views on freedom, property rights, and self-sovereignty. Among left-leaning progressives, Bitcoin is often quickly dismissed as irrelevant or a major source of carbon emissions. Bitcoin seems, however, to be full of surprises. A rapidly advancing body of anecdotal evidence suggests that its adoption may affect causes important to progressives, mitigating greenhouse gas emissions, accelerating electrification of economies, alleviating poverty, and supporting human rights for people living under political repression, even though scientific confirmation is lagging. In this paper, I highlight how a Pragmatist perspective can be applied to Bitcoin, a technological and financial innovation that may well reshape how humans perceive and use money, preserve wealth, and structure governance. I first cover Bitcoin’s technological and financial fundamentals and some core concepts of Pragmatism, before outlining how Bitcoin might surprise progressives. Pragmatism offers a philosophical and political grounding for left-leaning “progressive Bitcoiners” who prioritize environmental and social well-being and view inclusive deliberative democracy as the preferred form of governance.
Investigation of the Properties of Mo/ZSM-5 Catalysts Based on Zeolites with Microporous and Micro–Mesoporous Structures
Authors: Stepanov Andrey A. , Korobitsyna Ludmila L. , Vosmerikov Alexander V.
Published: May 2023

The dehydroaromatization of methane (MDA) is of great interest as a promising process for processing natural and associated petroleum gases, the main component of which is methane. The rapid loss of catalyst activity because of coke formation hinders the introduction of the DHA methane process into the industry. Therefore, the aim of this research was to find ways to improve Mo/ZSM-5 catalysts for MDA. The paper presents the results of the synthesis of high-silica zeolites of the ZSM-5 type with microporous and micro–mesoporous structures, the preparation of Mo/ZSM-5 catalysts based on them, and the study of the physicochemical and catalytic properties of the obtained samples during the non-oxidative conversion of methane into aromatic hydrocarbons. Zeolite catalysts were investigated using IR spectroscopy, X-ray diffraction, TPD-NH3, SEM, HR-TEM, and N2 adsorption. It was found that the addition of carbon black in the stage of the synthesis of zeolite type ZSM-5 did not lead to structural changes, and the obtained samples had a crystallinity degree equal to 100%. The creation of the micro–mesoporous structure in Mo/ZSM-5 catalysts led to an increase in their activity and stability in the process of methane dehydroaromatization. The highest conversion of methane was observed on a 4.0%Mo/ZSM-5 catalyst prepared based on zeolite synthesized using 1.0% carbon black and was 13.0% after 20 min of reaction, while the benzene yield reached 7.0%. It was shown using HR-TEM that a more uniform distribution of the active metal component was observed in a zeolite catalyst with a micro–mesoporous structure than in a microporous zeolite.
Heart Failure Post-SARS-CoV-2 Infection in Children with Duchenne Muscular Dystrophy: The Additive Value of Cardiovascular Magnetic Resonance
Authors: Markousis-Mavrogenis George , Belegrinos Antonios , Giannakopoulou Aikaterini , Karanasios Evangelos , Vartela Vasiliki , Patsilinakou Elephtheria , Samantis Paul , Pons Roser-Marie , Papavasiliou Antigoni , Mavrogeni Sophie I.
Published: May 2023

In this case series, we describe the diagnosis of post-COVID-19 myocarditis in asymptomatic patients with Duchenne Muscular Dystrophy (DMD) and a mild COVID-19 disease course. These patients were referred for CMR due to electrocardiographic and echocardiographic alterations, which did not exist before COVID-19 infection. CMR identified the presence of severe myocardial inflammation in all patients based on abnormally elevated myocardial T2 ratio, late gadolinium enhancement, native T1 mapping, T2 mapping, and extracellular volume fraction. This was paired with concurrent impairment of left ventricular function. Appropriate treatment was initiated in all cases. Two of the four patients developed episodes of ventricular tachycardia during the following 6 months, and a defibrillator was implanted. Despite the mild clinical presentation, this case series demonstrates the diagnostic strength of CMR in the diagnosis and evaluation of post-COVID-19 myocarditis and serves to increase awareness of this potential complication amongst treating physicians.
Dentists’ Perspective on the Impact of COVID-19 on the Utilization of Emergency Dental Services in Kuwait: A Cross-Sectional Study
Authors: Alonaizi Nour , Alharran Sarah , Baskaradoss Jagan Kumar
Published: May 2023

This cross-sectional study intends to evaluate dentists’ perceptions of COVID-19’s effects on the use of emergency dental care both during and after Kuwait’s lockdown periods. A convenience sample of dentists employed by the Ministry of Health’s various emergency dental clinics and School Oral Health Programs (SOHP) throughout Kuwait’s six governorates were invited to take part in this study. To determine the impact of various demographic and occupational characteristics on the mean perception score of the dentist, a multi-variable model was developed. The study was conducted between June–September 2021, and a total of 268 dentists (61% males and 39% females) participated in this study. When compared to pre-lockdown periods, the overall number of patients seen by dentists had significantly decreased after the lockdown period. After lockdown, there were significantly more cases of acute pulpitis with apical periodontitis, abscesses, and pericoronitis than there were before lockdown (p < 0.05). After the lockdown, a significantly higher percentage of dentists (p < 0.05) reported using fewer droplets-generating procedures to manage patients with dental emergencies. After correcting for the other variables in the model, female dentists (β = 0.146; 95% CI = 0.071 to 1.451) and non-Kuwaiti dentist (β = 0.012; 95% CI = 0.234 to 1.854) had a significantly (p < 0.05) more positive perception of the utilization of dental services than others after adjusting for the other variables in the model. The majority of dentists perceive that the COVID-19 pandemic has had a negative impact on Kuwait’s use of emergency dental services.
Salicylic-Zinc Nanocomposites with Enhanced Antibacterial Activity
Authors: Kang Sang Gu , Lee Kyung Eun , Singh Mahendra , Vinayagam Ramachandran
Published: May 2023

Numerous infectious diseases and microorganisms with high drug resistance have motivated researchers to develop nanocomposite particles as antimicrobial agents. Herein, we report on nanocomposites of salicylic acid (SA) and 5-sulfosalicylic acid (5-SSA) with zinc oxide (ZnO), namely SA-ZnO and 5-SSA-ZnO nanoparticles (NPs), with antibacterial and cytotoxic properties. Ultraviolet-visible and Fourier-transform infrared spectroscopy of the synthesized SA-ZnO and 5-SSA-ZnO NPs indicated the functionalization of ZnO with SA and 5-SSA. X-ray diffraction revealed the crystalline structures of the synthesized NPs. The zeta potentials of the SA-ZnO, 5-SSA-ZnO, and ZnO NPs were 1.42, −5.98, and −0.172, respectively. The SA-ZnO and 5-SSA-ZnO NPs were spherical. Besides, the results of the antimicrobial assay indicated a significant reduction (p < 0.05) in the growth of Escherichia coli and Bacillus cereus by SA-ZnO and 5-SSA-ZnO NPs (0.1%). Scanning electron microscopy of NP-treated bacteria revealed cell death. Moreover, SA-ZnO and 5-SSA-ZnO NPs did not exhibit substantial toxicity against human HaCaT cells even at a high concentration (200 µg/mL). Overall, SA-ZnO and 5-SSA-ZnO NPs exhibited antibiotic-mimicking activity against bacteria with no cytotoxicity.
Correction: Tong et al. Effect of Micro-Textures on the Surface Interaction of WC+Co Alloy Composite Coatings. Coatings 2022, 12, 1242
Authors: Tong Xin , Zhang Yu , Yu Xiaoyang
Published: May 2023

Affiliation Correction [...]
Social Learning and the Exploration-Exploitation Tradeoff
Authors: Mintz Brian , Fu Feng
Published: May 2023

Cultures around the world show varying levels of conservatism. While maintaining traditional ideas prevents wrong ones from being embraced, it also slows or prevents adaptation to new times. Without exploration there can be no improvement, but often this effort is wasted as it fails to produce better results, making it better to exploit the best known option. This tension is known as the exploration/exploitation issue, and it occurs at the individual and group levels, whenever decisions are made. As such, it is has been investigated across many disciplines. We extend previous work by approximating a continuum of traits under local exploration, employing the method of adaptive dynamics, and studying multiple fitness functions. In this work, we ask how nature would solve the exploration/exploitation issue, by allowing natural selection to operate on an exploration parameter in a variety of contexts, thinking of exploration as mutation in a trait space with a varying fitness function. Specifically, we study how exploration rates evolve by applying adaptive dynamics to the replicator-mutator equation, under two types of fitness functions. For the first, payoffs are accrued from playing a two-player, two-action symmetric game, we consider representatives of all games in this class, including the Prisoner’s Dilemma, Hawk-Dove, and Stag Hunt games, finding exploration rates often evolve downwards, but can also undergo neutral selection as well depending on the games parameters or initial conditions. Second, we study time dependent fitness with a function having a single oscillating peak. By increasing the period, we see a jump in the optimal exploration rate, which then decreases towards zero as the frequency of environmental change increases. These results establish several possible evolutionary scenarios for exploration rates, providing insight into many applications, including why we can see such diversity in rates of cultural change.
Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?
Authors: Spitaleri Gianluca , Trillo Aliaga Pamela , Attili Ilaria , Del Signore Ester , Corvaja Carla , Corti Chiara , Crimini Edoardo , Passaro Antonio , de Marinis Filippo
Published: May 2023

ALK translocation amounts to around 3–7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.
The Effect of Lung Resection for NSCLC on Circulating Immune Cells: A Pilot Study
Authors: Phillips Joseph D. , Fay Kayla A. , Bergeron Alan J. , Zhang Peisheng , Mielcarz Daniel W. , Calkins Andrew M. , Searles Tyler G. , Christensen Brock C. , Finley David J. , Turk Mary Jo , Channon Jacqueline Y.
Published: May 2023

This pilot study sought to evaluate the circulating levels of immune cells, particularly regulatory T-cell (Treg) subsets, before and after lung resection for non-small cell lung cancer. Twenty-five patients consented and had specimens collected. Initially, peripheral blood of 21 patients was collected for circulating immune cell studies. Two of these patients were excluded due to technical issues, leaving 19 patients for the analyses of circulating immune cells. Standard gating and high-dimensional unsupervised clustering flow cytometry analyses were performed. The blood, tumors and lymph nodes were analyzed via single-cell RNA and TCR sequencing for Treg analyses in a total of five patients (including four additional patients from the initial 21 patients). Standard gating flow cytometry revealed a transient increase in neutrophils immediately following surgery, with a variable neutrophil–lymphocyte ratio and a stable CD4–CD8 ratio. Unexpectedly, the total Treg and Treg subsets did not change with surgery with standard gating in short- or long-term follow-up. Similarly, unsupervised clustering of Tregs revealed a dominant cluster that was stable perioperatively and long-term. Two small FoxP3hi clusters slightly increased following surgery. In the longer-term follow-up, these small FoxP3hi Treg clusters were not identified, indicating that they were likely a response to surgery. Single-cell sequencing demonstrated six CD4+FoxP3+ clusters among the blood, tumors and lymph nodes. These clusters had a variable expression of FoxP3, and several were mainly, or only, present in tumor and lymph node tissue. As such, serial monitoring of circulating Tregs may be informative, but not completely reflective of the Tregs present in the tumor microenvironment.
Metabarcoding Extends the Distribution of Porphyra corallicola (Bangiales) into the Arctic While Revealing Novel Species and Patterns for Conchocelis Stages in the Canadian Flora
Authors: Saunders Gary W. , Brooks Cody M.
Published: May 2023

Porphyra corallicola was described based on a filamentous red alga inadvertently introduced into culture from a crustose coralline alga. This species is known only in its sporophyte (Conchocelis) stage, being possibly asexual and lacking the charismatic and “collectable” gametophyte stage. Consequently, little is known of its range and distribution. Taxon-targeted metabarcoding was explored as a pathway to gain insights into the vertical (intertidal versus subtidal) and biogeographical distribution of this species, as well as to assess host diversity. We also wanted to ascertain if other species occur in only the Conchocelis stage in the Canadian flora. Primers targeting a short (521 bp) region of the plastid rbcL gene in the Bangiales were used to screen DNA from 285 coralline crusts collected throughout Canada and adjacent waters. In addition to confirming the presence of P. corallicola in the Bay of Fundy, this species was recovered from coralline crusts along the coast of Nova Scotia (n = 1) and in the low Arctic (Labrador; n = 2), greatly extending its range and suggesting it is a cold-water taxon. We have confirmed its presence in both the low intertidal and subtidal (to 10 m), and its occurrence in three different coralline species, suggesting that it lacks host specificity. In total, nine genetic groups of Bangiales were uncovered in our survey, six matching entries currently in GenBank and three apparently novel genetic groups—two from the northeast Pacific and one from the low Arctic. Notable host and ecological patterns are discussed. This method, when further developed, will facilitate the study of Conchocelis stages in nature, which will greatly enhance ecological knowledge of bangialean species.
A Review of the Configurations, Capabilities, and Cutting-Edge Options for Multistage Solar Stills in Water Desalination
Authors: Rashid Farhan Lafta , Kaood Amr , Al-Obaidi Mudhar A. , Mohammed Hayder I. , Alsarayreh Alanood A. , Al-Muhsen Nizar F. O. , Abbas Ammar S. , Zubo Rana H. A. , Mohammad Abdulrahman Th. , Alsadaie Salih , Sowgath Md. Tanvir , Abd-Alhameed Raed , Mujtaba Iqbal M.
Published: May 2023

The desalination of saltwater is a viable option to produce freshwater. All the desalination processes are energy-intensive and can be carried out on a large scale. Therefore, producing freshwater using renewable energy sources is the most desirable option considering the current energy crisis and the effect that fossil-fuel-based energy has on our carbon footprint. In this respect, the tray-type still, one of several solar power desalination still varieties, is popular owing to its straightforward design, economic materials of construction, and minimal maintenance requirements, especially in isolated island regions with restricted energy and natural water supplies. The traditional tray-type solar power has a few drawbacks, such as the inability to recover latent heat from condensation, reduced thermal convection, a large heat capacity, and comparatively minimal driving power through evaporation. Therefore, the improvement of heat and mass transfer capabilities in tray-type stills has been the subject of many studies. However, there is a lack of a comprehensive review in the open literature that covers the design and operational details of multistage solar stills. The purpose of this paper is to present a thorough overview of the past research on multistage solar stills, in terms of configurations, capabilities, and cutting-edge options. In comparison to a unit without a salt-blocking formation, the review indicates that a multistage distillation unit may run continuously at high radiation and generate pure water that is around 1.7 times higher than a unit without a salt-blocking formation. The most effective deign is found to be “V”-shaped solar still trays that attach to four-stage stills, since they are less expensive and more economical than the “floor” (Λ-shape) design, which requires two collectors. Additionally, it can be stated that the unit thermal efficiency, solar percentage, and collected solar energy (over the course of a year) increase by 23%, 18%, and 24%, respectively, when the solar collectors are increased by 26% (at the constant inflow velocity of the water).
The Role of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Tuberous Vas Deferens Tuberculosis and Metastatic Inguinal Lymph Nodes
Authors: Zhang Wenzhi , Ni Tu , Tang Wei , Yang Gaoyi
Published: May 2023

Purpose: To retrospective analysis and summary the features of tuberous vas deferens tuberculosis (VD TB) and inguinal metastatic lymph nodes (MLN) in routine ultrasound (US) and contrast-enhanced US (CEUS) as well as to assess the utility of CEUS in differentiating between the two diseases. Methods: The US and CEUS findings of patients with pathologically confirmed tuberous VD TB (n = 17) and inguinal MLN (n = 28), including the number of lesions, presence of bilateral disease, differences in internal echogenicity, a conglomeration of lesions, and blood flow within the lesions, were retrospectively analyzed. Results: Routine US showed no significant difference in the number of lesions, nodule size, internal echogenicity, sinus tract, or skin rupture; however, significant differences were observed between the two conditions in the conglomeration of lesions (χ2 = 6.455; p = 0.023) and the degree, intensity, and echogenicity pattern on CEUS (χ2 = 18.865, 17.455, and 15.074, respectively; p = 0.000 for all). Conclusions: CEUS can show the blood supply of the lesion, and judge the physical condition of the lesion better than US. Homogeneous, centripetal, and diffuse enhancement should prompt a diagnosis of inguinal MLN, whereas lesions with heterogeneous and diffuse enhancement on CEUS should be considered as VD TB. CEUS has great diagnostic value in differentiating between tuberous VD TB and inguinal MLN.
Distinguishing Parkinson’s Disease with GLCM Features from the Hankelization of EEG Signals
Authors: Karakaş Mehmet Fatih , Latifoğlu Fatma
Published: May 2023

This study proposes a novel method that uses electroencephalography (EEG) signals to classify Parkinson’s Disease (PD) and demographically matched healthy control groups. The method utilizes the reduced beta activity and amplitude decrease in EEG signals that are associated with PD. The study involved 61 PD patients and 61 demographically matched controls groups, and EEG signals were recorded in various conditions (eyes closed, eyes open, eyes both open and closed, on-drug, off-drug) from three publicly available EEG data sources (New Mexico, Iowa, and Turku). The preprocessed EEG signals were classified using features obtained from gray-level co-occurrence matrix (GLCM) features through the Hankelization of EEG signals. The performance of classifiers with these novel features was evaluated using extensive cross-validations (CV) and leave-one-out cross-validation (LOOCV) schemes. This method under 10 × 10 fold CV, the method was able to differentiate PD groups from healthy control groups using a support vector machine (SVM) with an accuracy of 92.4 ± 0.01, 85.7 ± 0.02, and 77.1 ± 0.06 for New Mexico, Iowa, and Turku datasets, respectively. After a head-to-head comparison with state-of-the-art methods, this study showed an increase in the classification of PD and controls.
Serial Dependence in Dermatological Judgments
Authors: Ren Zhihang , Li Xinyu , Pietralla Dana , Manassi Mauro , Whitney David
Published: May 2023

Serial Dependence is a ubiquitous visual phenomenon in which sequentially viewed images appear more similar than they actually are, thus facilitating an efficient and stable perceptual experience in human observers. Although serial dependence is adaptive and beneficial in the naturally autocorrelated visual world, a smoothing perceptual experience, it might turn maladaptive in artificial circumstances, such as medical image perception tasks, where visual stimuli are randomly sequenced. Here, we analyzed 758,139 skin cancer diagnostic records from an online app, and we quantified the semantic similarity between sequential dermatology images using a computer vision model as well as human raters. We then tested whether serial dependence in perception occurs in dermatological judgments as a function of image similarity. We found significant serial dependence in perceptual discrimination judgments of lesion malignancy. Moreover, the serial dependence was tuned to the similarity in the images, and it decayed over time. The results indicate that relatively realistic store-and-forward dermatology judgments may be biased by serial dependence. These findings help in understanding one potential source of systematic bias and errors in medical image perception tasks and hint at useful approaches that could alleviate the errors due to serial dependence.
Developing a Supplementary Diagnostic Tool for Breast Cancer Risk Estimation Using Ensemble Transfer Learning
Authors: Hanis Tengku Muhammad , Ruhaiyem Nur Intan Raihana , Arifin Wan Nor , Haron Juhara , Wan Abdul Rahman Wan Faiziah , Abdullah Rosni , Musa Kamarul Imran
Published: May 2023

Breast cancer is the most prevalent cancer worldwide. Thus, it is necessary to improve the efficiency of the medical workflow of the disease. Therefore, this study aims to develop a supplementary diagnostic tool for radiologists using ensemble transfer learning and digital mammograms. The digital mammograms and their associated information were collected from the department of radiology and pathology at Hospital Universiti Sains Malaysia. Thirteen pre-trained networks were selected and tested in this study. ResNet101V2 and ResNet152 had the highest mean PR-AUC, MobileNetV3Small and ResNet152 had the highest mean precision, ResNet101 had the highest mean F1 score, and ResNet152 and ResNet152V2 had the highest mean Youden J index. Subsequently, three ensemble models were developed using the top three pre-trained networks whose ranking was based on PR-AUC values, precision, and F1 scores. The final ensemble model, which consisted of Resnet101, Resnet152, and ResNet50V2, had a mean precision value, F1 score, and Youden J index of 0.82, 0.68, and 0.12, respectively. Additionally, the final model demonstrated balanced performance across mammographic density. In conclusion, this study demonstrates the good performance of ensemble transfer learning and digital mammograms in breast cancer risk estimation. This model can be utilised as a supplementary diagnostic tool for radiologists, thus reducing their workloads and further improving the medical workflow in the screening and diagnosis of breast cancer.