bluuebunny/crossref_metadata_2025 huggingface dataset:
Isogenic Cell Lines Derived from Specific Organ Metastases Exhibit Divergent Cytogenomic Aberrations
Authors: Winnard Paul T. , Morsberger Laura , Yonescu Raluca , Jiang Liqun , Zou Ying S. , Raman Venu
Published: February 2023

Aneuploidy, a deviation in chromosome numbers from the normal diploid set, is now recognized as a fundamental characteristic of all cancer types and is found in 70–90% of all solid tumors. The majority of aneuploidies are generated by chromosomal instability (CIN). CIN/aneuploidy is an independent prognostic marker of cancer survival and is a cause of drug resistance. Hence, ongoing research has been directed towards the development of therapeutics aimed at targeting CIN/aneuploidy. However, there are relatively limited reports on the evolution of CIN/aneuploidies within or across metastatic lesions. In this work, we built on our previous studies using a human xenograft model system of metastatic disease in mice that is based on isogenic cell lines derived from the primary tumor and specific metastatic organs (brain, liver, lung, and spine). As such, these studies were aimed at exploring distinctions and commonalities between the karyotypes; biological processes that have been implicated in CIN; single-nucleotide polymorphisms (SNPs); losses, gains, and amplifications of chromosomal regions; and gene mutation variants across these cell lines. Substantial amounts of inter- and intra-heterogeneity were found across karyotypes, along with distinctions between SNP frequencies across each chromosome of each metastatic cell line relative the primary tumor cell line. There were disconnects between chromosomal gains or amplifications and protein levels of the genes in those regions. However, commonalities across all cell lines provide opportunities to select biological processes as druggable targets that could have efficacy against the primary tumor, as well as metastases.
Advances in Urological Cancer in 2022, from Basic Approaches to Clinical Management
Authors: Manini Claudia , López-Fernández Estíbaliz , López José I. , Angulo Javier C.
Published: February 2023

This Special Issue includes 12 articles and 3 reviews dealing with several basic and clinical aspects of prostate, renal, and urinary tract cancer published during 2022 in Cancers, and intends to serve as a multidisciplinary chance to share the last advances in urological neoplasms [...]
Tolerability of BRAF and MEK Inhibitors for Metastasized Melanoma after Intra-Class Switch: A Multicenter, Retrospective Study
Authors: Salzmann Martin , Wald Alexander , Stege Henner , Loquai Carmen , Zimmer Lisa , Hayani Kinan M. , Heinzerling Lucie , Gutzmer Ralf , Enk Alexander H. , Hassel Jessica C.
Published: February 2023

Targeted therapy with BRAF and MEK inhibitors (BRAFi, MEKi) is one of the mainstays of melanoma treatment. When dose-limiting toxicity (DLT) is observed, an option represents the intra-class switch to a different BRAFi+MEKi combination. Currently, there is scarce evidence for this procedure. This is a multicenter, retrospective analysis from six German skin cancer centers of patients who received two different combinations of BRAFi and MEKi. In total, 94 patients were included: 38 patients (40%) were re-exposed with a different combination because of previous unacceptable toxicity, 51 (54%) were re-exposed after progression, and 5 (5%) were included for other reasons. Of the 44 patients with a DLT during their first BRAFi+MEKi combination, only five (11%) experienced the same DLT during their second combination. A new DLT was experienced by 13 patients (30%). Six patients (14%) had to discontinue the second BRAFi treatment due to its toxicity. Compound-specific adverse events were avoided in the majority of patients by switching to a different combination. Efficacy data were similar to historical cohorts of BRAFi+MEKi rechallenge, with an overall response rate of 31% for patients who had previously progressed to treatment. We conclude that switching to a different BRAFi+MEKi combination if dose-limiting toxicity occurs is a feasible and rational approach in patients with metastatic melanoma.
The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors
Authors: Xiao Wenlu , Huang Hao , Zheng Panpan , Liu Yingting , Chen Yaping , Chen Junjun , Zheng Xiao , Chen Lujun , Jiang Jingting
Published: February 2023

As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency ablation (RFA) side by analyzing single-cell RNA sequencing (scRNA-seq) data of tumor-bearing mice compared with control tumors. We showed that ablation treatment could increase the proportion of CD8+T cells and the interaction between macrophages and T cells was altered. Another thermal ablation treatment, microwave ablation (MWA), increased the enrichment of signaling pathways for chemotaxis and chemokine response and was associated with the chemokine CXCL10. In addition, the immune checkpoint PD-1 was especially up-regulated in the infiltrating T cells of tumors on the non-ablation side after thermal ablation treatment. Combination therapy of ablation and PD-1 blockade had a synergistic anti-tumor effect. Furthermore, we found that the CXCL10/CXCR3 axis contributed to the therapeutic efficacy of ablation combined with anti-PD-1 therapy, and activation of the CXCL10/CXCR3 signaling pathway might improve the synergistic effect of this combination treatment against solid tumors.
Computer-Aided Diagnosis of Melanoma Subtypes Using Reflectance Confocal Images
Authors: Mandal Ankita , Priyam Siddhaant , Chan Hsien Herbert , Gouveia Bruna Melhoranse , Guitera Pascale , Song Yang , Baker Matthew Arthur Barrington , Vafaee Fatemeh
Published: February 2023

Lentigo maligna (LM) is an early form of pre-invasive melanoma that predominantly affects sun-exposed areas such as the face. LM is highly treatable when identified early but has an ill-defined clinical border and a high rate of recurrence. Atypical intraepidermal melanocytic proliferation (AIMP), also known as atypical melanocytic hyperplasia (AMH), is a histological description that indicates melanocytic proliferation with uncertain malignant potential. Clinically and histologically, AIMP can be difficult to distinguish from LM, and indeed AIMP may, in some cases, progress to LM. The early diagnosis and distinction of LM from AIMP are important since LM requires a definitive treatment. Reflectance confocal microscopy (RCM) is an imaging technique often used to investigate these lesions non-invasively, without biopsy. However, RCM equipment is often not readily available, nor is the associated expertise for RCM image interpretation easy to find. Here, we implemented a machine learning classifier using popular convolutional neural network (CNN) architectures and demonstrated that it could correctly classify lesions between LM and AIMP on biopsy-confirmed RCM image stacks. We identified local z-projection (LZP) as a recent fast approach for projecting a 3D image into 2D while preserving information and achieved high-accuracy machine classification with minimal computational requirements.
Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre
Authors: Stares Mark , Lewis Georgina , Vallet Maheva , Killean Angus , Tramonti Giovanni , Patrizio Ailsa , Mackean Melanie , Harrow Stephen , Barrie Colin , MacLennan Kirsty , Campbell Sorcha , Evans Tamasin , Tufail Aisha ,   Edinburgh Cancer Informatics Programme, Hall Peter , Phillips Iain
Published: February 2023

Introduction: Stereotactic ablative body radiotherapy (SABR) offers patients with stage I non-small-cell lung cancer (NSCLC) a safe, effective radical therapy option. The impact of introducing SABR at a Scottish regional cancer centre was studied. Methods: The Edinburgh Cancer Centre Lung Cancer Database was assessed. Treatment patterns and outcomes were compared across treatment groups (no radical therapy (NRT), conventional radical radiotherapy (CRRT), SABR and surgery) and across three time periods reflecting the availability of SABR (A, January 2012/2013 (pre-SABR); B, 2014/2016 (introduction of SABR); C, 2017/2019, (SABR established)). Results: 1143 patients with stage I NSCLC were identified. Treatment was NRT in 361 (32%), CRRT in 182 (16%), SABR in 132 (12%) and surgery in 468 (41%) patients. Age, performance status, and comorbidities correlated with treatment choice. The median survival increased from 32.5 months in time period A to 38.8 months in period B to 48.8 months in time period C. The greatest improvement in survival was seen in patients treated with surgery between time periods A and C (HR 0.69 (95% CI 0.56–0.86), p < 0.001). The proportion of patients receiving a radical therapy rose between time periods A and C in younger (age ≤ 65, 65–74 and 75–84 years), fitter (PS 0 and 1), and less comorbid patients (CCI 0 and 1–2), but fell in other patient groups. Conclusions: The introduction and establishment of SABR for stage I NSCLC has improved survival outcomes in Southeast Scotland. Increasing SABR utilisation appears to have enhanced the selection of surgical patients and increased the proportion of patients receiving a radical therapy.
Value of Cellular Components and Focal Dedifferentiation to Predict the Risk of Metastasis in a Benign-Appearing Extra-Meningeal Solitary Fibrous Tumor: An Original Series from a Tertiary Sarcoma Center
Authors: Hassani Mohammad , Jung Sungmi , Ghodsi Elaheh , Seddigh Leila , Kooner Paul , Aoude Ahmed , Turcotte Robert
Published: February 2023

Histology has not been accepted as a valid predictor of the biological behavior of extra-meningeal solitary fibrous tumors (SFTs). Based on the lack of a histologic grading system, a risk stratification model is accepted by the WHO to predict the risk of metastasis; however, the model shows some limitations to predict the aggressive behavior of a low-risk/benign-appearing tumor. We conducted a retrospective study based on medical records of 51 primary extra-meningeal SFT patients treated surgically with a median follow-up of 60 months. Tumor size (p = 0.001), mitotic activity (p = 0.003), and cellular variants (p = 0.001) were statistically associated with the development of distant metastases. In cox regression analysis for metastasis outcome, a one-centimeter increment in tumor size enhanced the expected metastasis hazard by 21% during the follow-up time (HR = 1.21, CI 95% (1.08–1.35)), and each increase in the number of mitotic figures escalated the expected hazard of metastasis by 20% (HR = 1.2, CI 95% (1.06–1.34)). Recurrent SFTs presented with higher mitotic activity and increased the likelihood of distant metastasis (p = 0.003, HR = 12.68, CI 95% (2.31–69.5)). All SFTs with focal dedifferentiation developed metastases during follow-up. Our findings also revealed that assembling risk models based on a diagnostic biopsy underestimated the probability of developing metastasis in extra-meningeal SFTs.
Leveraging Tumor Microenvironment Infiltration in Pancreatic Cancer to Identify Gene Signatures Related to Prognosis and Immunotherapy Response
Authors: Yang Jiabin , Zeng Liangtang , Chen Ruiwan , Huang Leyi , Wu Zhuo , Yu Min , Zhou Yu , Chen Rufu
Published: February 2023

The hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant tumor microenvironment (TME) comprised of diverse cell types that play key roles in carcinogenesis, chemo-resistance, and immune evasion. Here, we propose a gene signature score through the characterization of cell components in TME for promoting personalized treatments and further identifying effective therapeutic targets. We identified three TME subtypes based on cell components quantified by single sample gene set enrichment analysis. A prognostic risk score model (TMEscore) was established based on TME-associated genes using a random forest algorithm and unsupervised clustering, followed by validation in immunotherapy cohorts from the GEO dataset for its performance in predicting prognosis. Importantly, TMEscore positively correlated with the expression of immunosuppressive checkpoints and negatively with the gene signature of T cells’ responses to IL2, IL15, and IL21. Subsequently, we further screened and verified F2R-like Trypsin Receptor1 (F2RL1) among the core genes related to TME, which promoted the malignant progression of PDAC and has been confirmed as a good biomarker with therapeutic potential in vitro and in vivo experiments. Taken together, we proposed a novel TMEscore for risk stratification and selection of PDAC patients in immunotherapy trials and validated effective pharmacological targets.
Facile Synthesis of a Bi2WO6/BiO2−x Heterojunction for Efficient Photocatalytic Degradation of Ciprofloxacin under Visible Light Irradiation
Authors: Zhang Hongzhong , Fan Zhaoya , Chai Qingqing , Li Jun
Published: February 2023

In this work, a Z-scheme Bi2WO6/BiO2−x heterojunction was successfully prepared using a self-assembly strategy. Various characterization techniques demonstrated that the formation of the heterojunction not only accelerated the separation of photoinduced carriers but also weakened the recombination rate of photogenerated electron–hole pairs-. The Bi2WO6/BiO2−x composites had a wider absorption edge than Bi2WO6 in the range of 200–800 nm, which improved the photocatalytic performance of ciprofloxacin (CIP) degradation under xenon lamps. As a result, the Z-scheme heterojunction Bi2WO6/BiO2−x composite exhibited excellent photocatalytic activity. Catalyzed by the optimal 20% Bi2WO6/BiO2−x (0.5 g/L), the removal rate of CIP (10.0 mg/L) was 91.8% within 2 h irradiated by visible light, which was 2.37 times that of the BiO2−x catalyst. This work will provide a fresh perspective on the construction of visible-driven Z-scheme photocatalysts for wastewater treatment.
MIL-53(Fe)@perylene Diimide All-Organic Heterojunctions for the Enhanced Photocatalytic Removal of Pollutants and Selective Oxidation of Benzyl Alcohol
Authors: Shi Kaiyang , Wang Fulin , Li Xiangwei , Huang Weiya , Lu Kang-Qiang , Yu Changlin , Yang Kai
Published: February 2023

Organic semiconductors are promising materials for the photocatalytic treatment of pollutants and organic synthesis. Herein, MIL-53(Fe)@perylene diimide (PDI) organic heterojunctions were constructed by ultrasonic assembly using PDI as the co-catalyst, and PDI organic supramolecular material was uniformly distributed on the surfaces of MIL-53(Fe). The most effective M53@PDI-20 organic heterojunctions achieved 72.7% photodegradation of rhodamine B (10 mg/L) within 50 min and a 99.9% reduction in Cr(VI) (10 mg/L) for 150 min, and the corresponding apparent degradation rate constants were higher than a single component. Meanwhile, the conversion rate of benzyl alcohol over M53@PDI-20 achieved 91.5% for 5 h with a selectivity of above 90% under visible light exposure, which was more than double that of PDI. The well-matched band structures and the strong π–π bonding interactions between MIL-53(Fe) and PDI can increase the electron delocalization effect to facilitate the transfer and separation of photogenerated carriers. Lots of oxidative reactive species (h+, •O2− and •OH) also played a great contribution to the strong oxidation capacity over the heterojunctions system. This work suggests that MIL-53(Fe)@PDI organic heterojunctions may be a promising material for pollutant removal and organic synthesis.
Ezrin and Its Phosphorylated Thr567 form Are Key Regulators of Human Extravillous Trophoblast Motility and Invasion
Authors: Tabrizi Maral E. A. , Gupta Janesh K. , Gross Stephane R.
Published: February 2023

The protein ezrin has been shown to enhance cancer cell motility and invasion leading to malignant behaviours in solid tumours, but a similar regulatory function in the early physiological reproduction state is, however, much less clear. We speculated that ezrin may play a key role in promoting first-trimester extravillous trophoblast (EVT) migration/invasion. Ezrin, as well as its Thr567 phosphorylation, were found in all trophoblasts studied, whether primary cells or lines. Interestingly, the proteins were seen in a distinct cellular localisation in long, extended protrusions in specific regions of cells. Loss-of-function experiments were carried out in EVT HTR8/SVneo and Swan71, as well as primary cells, using either ezrin siRNAs or the phosphorylation Thr567 inhibitor NSC668394, resulting in significant reductions in both cell motility and cellular invasion, albeit with differences between the cells used. Our analysis further demonstrated that an increase in focal adhesion was, in part, able to explain some of the molecular mechanisms involved. Data collected using human placental sections and protein lysates further showed that ezrin expression was significantly higher during the early stage of placentation and, importantly, clearly seen in the EVT anchoring columns, further supporting the potential role of ezrin in regulating migration and invasion in vivo.
Diagnostic and Prognostic Comparison of Immune-Complex-Mediated Membranoproliferative Glomerulonephritis and C3 Glomerulopathy
Authors: Kovala Marja , Seppälä Minna , Räisänen-Sokolowski Anne , Meri Seppo , Honkanen Eero , Kaartinen Kati
Published: February 2023

Membranoproliferative glomerulonephritis (MPGN) is subdivided into immune-complex-mediated glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G). Classically, MPGN has a membranoproliferative-type pattern, but other morphologies have also been described depending on the time course and phase of the disease. Our aim was to explore whether the two diseases are truly different, or merely represent the same disease process. All 60 eligible adult MPGN patients diagnosed between 2006 and 2017 in the Helsinki University Hospital district, Finland, were reviewed retrospectively and asked for a follow-up outpatient visit for extensive laboratory analyses. Thirty-seven (62%) had IC-MPGN and 23 (38%) C3G (including one patient with dense deposit disease, DDD). EGFR was below normal (≤60 mL/min/1.73 m2) in 67% of the entire study population, 58% had nephrotic range proteinuria, and a significant proportion had paraproteins in their serum or urine. A classical MPGN-type pattern was seen in only 34% of the whole study population and histological features were similarly distributed. Treatments at baseline or during follow-up did not differ between the groups, nor were there significant differences observed in complement activity or component levels at the follow-up visit. The risk of end-stage kidney disease and survival probability were similar in the groups. IC-MPGN and C3G have surprisingly similar characteristics, kidney and overall survival, which suggests that the current subdivision of MPGN does not add substantial clinical value to the assessment of renal prognosis. The high proportion of paraproteins in patient sera or in urine suggests their involvement in disease development.
A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation
Authors: Pacifici Francesca , Malatesta Gina , Mammi Caterina , Pastore Donatella , Marzolla Vincenzo , Ricordi Camillo , Chiereghin Francesca , Infante Marco , Donadel Giulia , Curcio Francesco , Noce Annalisa , Rovella Valentina , Lauro Davide , Tesauro Manfredi , Di Daniele Nicola , Garaci Enrico , Caprio Massimiliano , Della-Morte David
Published: February 2023

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5+) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5+, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5+ administration significantly reduced lipids’ accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5+ inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5+ significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5+ may be able to counteract adipogenesis and then obesity by inducing fat browning.
Sarcoplasmic Reticulum Ca2+ Buffer Proteins: A Focus on the Yet-To-Be-Explored Role of Sarcalumenin in Skeletal Muscle Health and Disease
Authors: Conte Elena , Dinoi Giorgia , Imbrici Paola , De Luca Annamaria , Liantonio Antonella
Published: February 2023

Sarcalumenin (SAR) is a luminal Ca2+ buffer protein with high capacity but low affinity for calcium binding found predominantly in the longitudinal sarcoplasmic reticulum (SR) of fast- and slow-twitch skeletal muscles and the heart. Together with other luminal Ca2+ buffer proteins, SAR plays a critical role in modulation of Ca2+ uptake and Ca2+ release during excitation–contraction coupling in muscle fibers. SAR appears to be important in a wide range of other physiological functions, such as Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) stabilization, Store-Operated-Calcium-Entry (SOCE) mechanisms, muscle fatigue resistance and muscle development. The function and structural features of SAR are very similar to those of calsequestrin (CSQ), the most abundant and well-characterized Ca2+ buffer protein of junctional SR. Despite the structural and functional similarity, very few targeted studies are available in the literature. The present review provides an overview of the role of SAR in skeletal muscle physiology, as well as of its possible involvement and dysfunction in muscle wasting disorders, in order to summarize the current knowledge on SAR and drive attention to this important but still underinvestigated/neglected protein.
cAMP Compartmentalisation in Human Myometrial Cells
Authors: Varley Alice , Koschinski Andreas , Johnson Mark R. , Zaccolo Manuela
Published: February 2023

Preterm birth is the leading cause of childhood mortality and morbidity. A better understanding of the processes that drive the onset of human labour is essential to reduce the adverse perinatal outcomes associated with dysfunctional labour. Beta-mimetics, which activate the myometrial cyclic adenosine monophosphate (cAMP) system, successfully delay preterm labour, suggesting a key role for cAMP in the control of myometrial contractility; however, the mechanisms underpinning this regulation are incompletely understood. Here we used genetically encoded cAMP reporters to investigate cAMP signalling in human myometrial smooth muscle cells at the subcellular level. We found significant differences in the dynamics of the cAMP response in the cytosol and at the plasmalemma upon stimulation with catecholamines or prostaglandins, indicating compartment-specific handling of cAMP signals. Our analysis uncovered significant disparities in the amplitude, kinetics, and regulation of cAMP signals in primary myometrial cells obtained from pregnant donors compared with a myometrial cell line and found marked response variability between donors. We also found that in vitro passaging of primary myometrial cells had a profound impact on cAMP signalling. Our findings highlight the importance of cell model choice and culture conditions when studying cAMP signalling in myometrial cells and we provide new insights into the spatial and temporal dynamics of cAMP in the human myometrium.
Insights into the Role of a Cardiomyopathy-Causing Genetic Variant in ACTN2
Authors: Broadway-Stringer Sophie , Jiang He , Wadmore Kirsty , Hooper Charlotte , Douglas Gillian , Steeples Violetta , Azad Amar J. , Singer Evie , Reyat Jasmeet S. , Galatik Frantisek , Ehler Elisabeth , Bennett Pauline , Kalisch-Smith Jacinta I. , Sparrow Duncan B. , Davies Benjamin , Djinovic-Carugo Kristina , Gautel Mathias , Watkins Hugh , Gehmlich Katja
Published: February 2023

Pathogenic variants in ACTN2, coding for alpha-actinin 2, are known to be rare causes of Hypertrophic Cardiomyopathy. However, little is known about the underlying disease mechanisms. Adult heterozygous mice carrying the Actn2 p.Met228Thr variant were phenotyped by echocardiography. For homozygous mice, viable E15.5 embryonic hearts were analysed by High Resolution Episcopic Microscopy and wholemount staining, complemented by unbiased proteomics, qPCR and Western blotting. Heterozygous Actn2 p.Met228Thr mice have no overt phenotype. Only mature males show molecular parameters indicative of cardiomyopathy. By contrast, the variant is embryonically lethal in the homozygous setting and E15.5 hearts show multiple morphological abnormalities. Molecular analyses, including unbiased proteomics, identified quantitative abnormalities in sarcomeric parameters, cell-cycle defects and mitochondrial dysfunction. The mutant alpha-actinin protein is found to be destabilised, associated with increased activity of the ubiquitin-proteasomal system. This missense variant in alpha-actinin renders the protein less stable. In response, the ubiquitin-proteasomal system is activated; a mechanism that has been implicated in cardiomyopathies previously. In parallel, a lack of functional alpha-actinin is thought to cause energetic defects through mitochondrial dysfunction. This seems, together with cell-cycle defects, the likely cause of the death of the embryos. The defects also have wide-ranging morphological consequences.
Role of Astrocytes in the Pathophysiology of Lafora Disease and Other Glycogen Storage Disorders
Authors: Duran Jordi
Published: February 2023

Lafora disease is a rare disorder caused by loss of function mutations in either the EPM2A or NHLRC1 gene. The initial symptoms of this condition are most commonly epileptic seizures, but the disease progresses rapidly with dementia, neuropsychiatric symptoms, and cognitive deterioration and has a fatal outcome within 5–10 years after onset. The hallmark of the disease is the accumulation of poorly branched glycogen in the form of aggregates known as Lafora bodies in the brain and other tissues. Several reports have demonstrated that the accumulation of this abnormal glycogen underlies all the pathologic traits of the disease. For decades, Lafora bodies were thought to accumulate exclusively in neurons. However, it was recently identified that most of these glycogen aggregates are present in astrocytes. Importantly, astrocytic Lafora bodies have been shown to contribute to pathology in Lafora disease. These results identify a primary role of astrocytes in the pathophysiology of Lafora disease and have important implications for other conditions in which glycogen abnormally accumulates in astrocytes, such as Adult Polyglucosan Body disease and the buildup of Corpora amylacea in aged brains.
Statistical Amplification of the Effects of Weak Magnetic Fields in Cellular Translation
Authors: Binhi Vladimir N.
Published: February 2023

We assume that the enzymatic processes of recognition of amino acids and their addition to the synthesized molecule in cellular translation include the formation of intermediate pairs of radicals with spin-correlated electrons. The mathematical model presented describes the changes in the probability of incorrectly synthesized molecules in response to a change in the external weak magnetic field. A relatively high chance of errors has been shown to arise from the statistical enhancement of the low probability of local incorporation errors. This statistical mechanism does not require a long thermal relaxation time of electron spins of about 1 μs—a conjecture often used to match theoretical models of magnetoreception with experiments. The statistical mechanism allows for experimental verification by testing the usual Radical Pair Mechanism properties. In addition, this mechanism localizes the site where magnetic effects originate, the ribosome, which makes it possible to verify it by biochemical methods. This mechanism predicts a random nature of the nonspecific effects caused by weak and hypomagnetic fields and agrees with the diversity of biological responses to a weak magnetic field.
Effect of UV Irradiation on the Growth of ZnO:Er Nanorods and Their Intrinsic Defects
Authors: Buryi Maksym , Ridzoňová Katarína , Neykova Neda , Landová Lucie , Hájek František , Babin Vladimir , Děcká Kateřina , Sharma Rupendra Kumar , Pop-Georgievski Ognen
Published: February 2023

Nanorods of erbium-doped zinc oxide (ZnO:Er) were fabricated using a hydrothermal method. One batch was prepared with and another one without constant ultraviolet (UV) irradiation applied during the growth. The nanorods were free-standing (FS) as well as deposited onto a fused silica glass substrate (GS). The goal was to study the atomistic aspects influencing the charge transport of ZnO nanoparticles, especially considering the differences between the FS and GS samples. We focused on the excitons; the intrinsic defects, such as zinc interstitials, zinc vacancies, and related shallow donors; and the conduction electrons. UV irradiation was applied for the first time during the ZnO:Er nanorod growth. This led to almost total exciton and zinc vacancy luminescence reduction, and the number of shallow donors was strongly suppressed in the GS samples. The effect was much less pronounced in the FS rods. Moreover, the exciton emission remained unchanged there. At the same time, the Er3+ content was decreased in the FS particles grown under constant UV irradiation while Er3+ was not detected in the GS particles at all. These phenomena are explained.
Measuring Importance of Physical Self-Care Behavior in Patients with Heart Failure: Validation and Reliability Analysis of IPSC-14 Item Scale
Authors: Tsami Athanasia , Koutelekos Ioannis , Gerogianni Georgia , Pavlatou Niki , Kalogianni Antonia , Kapadohos Theodore , Toulia Georgia , Polikandrioti Maria
Published: February 2023

Introduction: Heart failure (HF) is a complex clinical syndrome associated with increased disability, morbidity and mortality globally. HF is characterized by recurrent exacerbations and a high rate of hospital readmissions. Self-care is a crucial component of treatment. The way patients assess the importance of self-care may shed light on planning effective individualized interventions. The aim of this study was to conduct a validity and reliability analysis of the new 14-item IPSC scale, which measures how important HF patients consider their physical self-care behavior (IPSC, Importance of Physical Self-Care). Material and Methods: The 14-item IPSC scale was created by the researchers to explore how important HF patients consider their physical self-care behavior. The validation of the IPSC scale included face and content validity, construct validity, internal consistency, repeatability and discriminant validity. Patients’ characteristics were also included. Results: In the present study, 52 hospitalized HF patients were enrolled, of whom 55.8% were female, 34.6% above 70 years old, 48.1% of NYHA class III and 32.7% suffered this illness from 6 to 10 years. The total IPSC score had a possible range of 14–56, with higher scores indicating a low importance of self-care. The descriptive statistics in the IPSC scale showed a mean score of 27.9 ± 4.9 and a median score of 29, indicating that HF patients evaluated self-care behavior as moderately important. All items were found to be statistically significantly correlated with total scale scores (p ≤ 0.05), with correlation coefficients rho > 0.250, indicating moderate to strong correlations and meaning that all items are important in the calculation of the final score (construct validity). The internal consistency of the items that constituted the total score was found to be high (Cronbach’s a > 0.7). Furthermore, it was found that scores had high repeatability (p ≤ 0.001 and ICCs > 0.7). Regarding discriminant validity, a statistically significant association was observed between the importance of physical self-care behavior and both years suffering the illness (p = 0.007) and the NYHA class (p = 0.030). Conclusion: The 14-item IPSC scale is a reliable instrument that help nurses in clinical settings to gain a better and prompt understanding of the importance which patients invest in their physical self-care behavior.
An Overview of Technological Parameter Optimization in the Case of Laser Cladding
Authors: Wang Kaiming , Liu Wei , Hong Yuxiang , Sohan H. , Tong Yonggang , Hu Yongle , Zhang Mingjun , Zhang Jian , Xiang Dingding , Fu Hanguang , Ju Jiang
Published: February 2023

This review examines the methods used to optimize the process parameters of laser cladding, including traditional optimization algorithms such as single-factor, regression analysis, response surface, and Taguchi, as well as intelligent system optimization algorithms such as neural network models, genetic algorithms, support vector machines, the new non-dominance ranking genetic algorithm II, and particle swarm algorithms. The advantages and disadvantages of various laser cladding process optimization methods are analyzed and summarized. Finally, the development trend of optimization methods in the field of laser cladding is summarized and predicted. It is believed that the result would serve as a foundation for future studies on the preparation of high-quality laser cladding coatings.
On Fitting the Lomax Distribution: A Comparison between Minimum Distance Estimators and Other Estimation Techniques
Authors: Nombebe Thobeka , Allison James , Santana Leonard , Visagie Jaco
Published: February 2023

In this paper, we investigate the performance of a variety of frequentist estimation techniques for the scale and shape parameters of the Lomax distribution. These methods include traditional methods such as the maximum likelihood estimator and the method of moments estimator. A version of the maximum likelihood estimator adjusted for bias is included as well. Furthermore, an alternative moment-based estimation technique, the L-moment estimator, is included, along with three different minimum distance estimators. The finite sample performances of each of these estimators are compared in an extensive Monte Carlo study. We find that no single estimator outperforms its competitors uniformly. We recommend one of the minimum distance estimators for use with smaller samples, while a bias-reduced version of maximum likelihood estimation is recommended for use with larger samples. In addition, the desirable asymptotic properties of traditional maximum likelihood estimators make them appealing for larger samples. We include a practical application demonstrating the use of the described techniques on observed data.
Synthesis of a Novel Hydrazone of Thieno[2,3-d]pyrimidine Clubbed with Ninhydrin: X-ray Crystal Structure and Computational Investigations
Authors: Altowyan Mezna Saleh , Haukka Matti , Soliman Saied M. , Barakat Assem , Boraei Ahmed T. A. , Sopaih Manar
Published: February 2023

The novel hydrazone-containing thieno[2,3-d]pyrimidine, namely, N′-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)-2-(4-oxo-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazide 4 was synthesized in a very good yield from the reaction of the triketoester 1 or ninhydrin 2 with the exocyclic acetohydrazide 3 in methanol. Good-quality crystals of 4 were obtained by recrystallization of the compound from the DMF/MeOH solvent mixture. The target product 4 crystallized in the triclinic crystal system and P-1 space group. The topology analysis of molecular packing indicated that the H…H (30.4%), O…H (22.0%) and H…C (17.0%) contacts are the most dominant intermolecular interactions in the crystal of 4, while the O…H, N…H, H…C, N…C, O…C, C…C and O…O are the only contacts which have shorter interaction distances than the vdWs radii sum of the interacting atoms. The structure of 4 is optimized and the calculated structure showed good agreement with the experimental one. Additionally, MEP, HOMO, LUMO and the reactivity descriptors were calculated.
Magnetic Properties of C-Implanted and P-Implanted MgO Single Crystal: A Comparative Experimental and First-Principle Study
Authors: Wang Xingyu , Ma Chunlin , Zhou Weiping , Tan Weishi
Published: February 2023

The magnetic properties were investigated for C- and P-implanted MgO single crystals, which were irradiated by 80 keV C and P ions with the dose of 3 × 1017 ions/cm2. The magnetic properties of pristine MgO were apparently changed by C and P ion implantation. Room temperature ferromagnetism was presented in the C-implanted sample, while the P-implanted sample only displayed paramagnetism at 20 K. For the purpose of clarifying the correlation between the magnetic properties and microstructure, a comparative study was carried out using experimental and theoretical methods in both C and P ion-implanted samples. The defect types were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, photoluminescence, and absorption spectrum. The existence of intrinsic (Mg vacancies, O vacancies) and extrinsic (C-related and P-related) defects were verified by the experimental results. The magnetic properties induced by various single and composite defects were studied by first-principle calculations. The calculation results indicated that the configuration of VMg (Mg vacancy) + CO (C substitute O defect) was a key factor for the inducing ferromagnetic properties in C-implanted MgO. For the case of the P-implanted MgO, the configuration of P-related defects and intrinsic vacancies can only contribute to the total moment value but cannot induce ferromagnetism.
Correlation between Microstructure and Macromechanical Properties in Additive Manufacturing and Welding
Authors: Wang Qian , Fu Wei , Jin Feng , Lei Min , Shi Junmiao
Published: February 2023

We have recently published a Special Issue of “Correlation between Microstructure and Macromechanical Properties in Additive Manufacturing and Welding” [...]
Optimizing Cancer Survivorship Care: Examination of Factors Associated with Transition to Primary Care
Authors: Mukherjee Som. D. , Bainbridge Daryl , Hillis Christopher , Sussman Jonathan
Published: February 2023

Healthcare systems in Canada and elsewhere have identified the need to develop methods to effectively and safely transition appropriate cancer survivors to primary care. It is generally accepted that survivors with a low risk of adverse events, including recurrence and toxicity, should be more systematically identified and offered transition. There remains a lack of clarity about what constitutes an appropriate profile that would assist greater application in practice. To address this gap, we examined the clinical profiles of patients that were transitioned from a large regional cancer centre to the community. The factors examined included disease site, clinical stage, time since diagnosis/first consult, cancer treatments, and Edmonton Symptom Assessment System (ESAS) scores. In total, 2604 patients were identified as transitioned between 2013 and 2020. These patients tended to have common cancers (e.g., breast, endometrium, colorectal) that were generally of lower stage. Half of the patients had received chemotherapy and/or radiation treatment. Nearly one-third of survivors were transitioned within a year of first consult and a third after five years. Most patients reported minimal symptoms based on ESAS scores prior to being transitioned. This study represents one of the first to analyze the types of cancer patients that are being selected for transition to primary care.
Attention Deep Feature Extraction from Brain MRIs in Explainable Mode: DGXAINet
Authors: Taşcı Burak
Published: February 2023

Artificial intelligence models do not provide information about exactly how the predictions are reached. This lack of transparency is a major drawback. Particularly in medical applications, interest in explainable artificial intelligence (XAI), which helps to develop methods of visualizing, explaining, and analyzing deep learning models, has increased recently. With explainable artificial intelligence, it is possible to understand whether the solutions offered by deep learning techniques are safe. This paper aims to diagnose a fatal disease such as a brain tumor faster and more accurately using XAI methods. In this study, we preferred datasets that are widely used in the literature, such as the four-class kaggle brain tumor dataset (Dataset I) and the three-class figshare brain tumor dataset (Dataset II). To extract features, a pre-trained deep learning model is chosen. DenseNet201 is used as the feature extractor in this case. The proposed automated brain tumor detection model includes five stages. First, training of brain MR images with DenseNet201, the tumor area was segmented with GradCAM. The features were extracted from DenseNet201 trained using the exemplar method. Extracted features were selected with iterative neighborhood component (INCA) feature selector. Finally, the selected features were classified using support vector machine (SVM) with 10-fold cross-validation. An accuracy of 98.65% and 99.97%, were obtained for Datasets I and II, respectively. The proposed model obtained higher performance than the state-of-the-art methods and can be used to aid radiologists in their diagnosis.
Implementation of Exome Sequencing in Prenatal Diagnostics: Chances and Challenges
Authors: Janicki Ewa , De Rademaeker Marjan , Meunier Colombine , Boeckx Nele , Blaumeiser Bettina , Janssens Katrien
Published: February 2023

Whole exome sequencing (WES) has become part of the postnatal diagnostic work-up of both pediatric and adult patients with a range of disorders. In the last years, WES is slowly being implemented in the prenatal setting as well, although some hurdles remain, such as quantity and quality of input material, minimizing turn-around times, and ensuring consistent interpretation and reporting of variants. We present the results of 1 year of prenatal WES in a single genetic center. Twenty-eight fetus-parent trios were analyzed, of which seven (25%) showed a pathogenic or likely pathogenic variant that explained the fetal phenotype. Autosomal recessive (4), de novo (2) and dominantly inherited (1) mutations were detected. Prenatal rapid WES allows for a timely decision-making in the current pregnancy, adequate counseling with the possibility of preimplantation or prenatal genetic testing in future pregnancies and screening of the extended family. With a diagnostic yield in selected cases of 25% and a turn-around time under 4 weeks, rapid WES shows promise for becoming part of pregnancy care in fetuses with ultrasound anomalies in whom chromosomal microarray did not uncover the cause.
Metabolomics: A New Era in the Diagnosis or Prognosis of B-Cell Non-Hodgkin’s Lymphoma
Authors: Alfaifi Abdullah , Refai Mohammed Y. , Alsaadi Mohammed , Bahashwan Salem , Malhan Hafiz , Al-Kahiry Waiel , Dammag Enas , Ageel Ageel , Mahzary Amjed , Albiheyri Raed , Almehdar Hussein , Qadri Ishtiaq
Published: February 2023

A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin’s lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin’s lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called “metabolomics.” A patient’s phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin’s lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin’s lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin’s lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin’s lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.
Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma
Authors: Meliante Piero Giuseppe , Zoccali Federica , de Vincentiis Marco , Ralli Massimo , Petrella Carla , Fiore Marco , Minni Antonio , Barbato Christian
Published: February 2023

Programmed cell death ligand-1 (PD-L1) binds PD-1 on CD8+ lymphocytes, inhibiting their cytotoxic action. Its aberrant expression by head and neck squamous cell carcinoma (HNSCC) cells leads to immune escape. Pembrolizumab and nivolumab, two humanized monoclonal antibodies against PD-1, have been approved in HNSCC treatment, but ~60% of patients with recurrent or metastatic HNSCC fail to respond to immunotherapy and only 20 to 30% of treated patients have long-term benefits. The purpose of this review is to analyze all the fragmentary evidence present in the literature to identify what future diagnostic markers could be useful for predicting, together with PD-L1 CPS, the response to immunotherapy and its durability. We searched PubMed, Embase, and the Cochrane Register of Controlled Trials and we summarize the evidence collected in this review. We confirmed that PD-L1 CPS is a predictor of response to immunotherapy, but it should be measured across multiple biopsies and repeatedly over time. PD-L2, IFN-γ, EGFR, VEGF, TGF–β, TMB, blood TMB, CD73, TILs, alternative splicing, tumor microenvironment, and some macroscopic and radiological features are promising predictors worthy of further studies. Studies comparing predictors appear to give greater potency to TMB and CXCR9.