bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Upregulation of SIRT1 Expression in Retinal Ganglion Cells by AAV-Mediated Gene Delivery Increases Neuronal Cell Survival and Alleviates Axon Demyelination Associated with Optic Neuritis
Authors: Ross Ahmara G. , Chaqour Brahim , McDougald Devin S. , Dine Kimberly E. , Duong Thu T. , Shindler Ryan E. , Yue Jipeng , Liu Tehui , Shindler Kenneth S.
Published: June 2022

Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration of retinal ganglion cells (RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON disease etiology is not known, changes in the redox system and exacerbated optic nerve inflammation play a major role in the pathogenesis of the disease. Silent information regulator 1 (sirtuin-1/SIRT1) is a ubiquitously expressed NAD+-dependent deacetylase, which functions to reduce/prevent both oxidative stress and inflammation in various tissues. Non-specific upregulation of SIRT1 by pharmacologic and genetic approaches attenuates RGC loss in experimental ON. Herein, we hypothesized that targeted expression of SIRT1 selectively in RGCs using an adeno-associated virus (AAV) vector as a delivery vehicle is an effective approach to reducing neurodegeneration and preserving vision in ON. We tested this hypothesis through intravitreal injection of AAV7m8.SNCG.SIRT1, an AAV2-derived vector optimized for highly efficient SIRT1 transgene transfer and protein expression into RGCs in mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis that recapitulates optic neuritis RGC loss and axon demyelination. Our data show that EAE mice injected with a control vehicle exhibit progressive alteration of visual function reflected by decreasing optokinetic response (OKR) scores, whereas comparatively, AAV7m8.SNCG.SIRT1-injected EAE mice maintain higher OKR scores, suggesting that SIRT1 reduces the visual deficit imparted by EAE. Consistent with this, RGC survival determined by immunolabeling is increased and axon demyelination is decreased in the AAV7m8.SNCG.SIRT1 RGC-injected group of EAE mice compared to the mouse EAE counterpart injected with a vehicle or with control vector AAV7m8.SNCG.eGFP. However, immune cell infiltration of the optic nerve is not significantly different among all EAE groups of mice injected with either vehicle or AAV7m8.SNCG.SIRT1. We conclude that despite minimally affecting the inflammatory response in the optic nerve, AAV7m8-mediated SIRT1 transfer into RGCs has a neuroprotective potential against RGC loss, axon demyelination and vison deficits associated with EAE. Together, these data suggest that SIRT1 exerts direct effects on RGC survival and function.
High-Risk Acute Myeloid Leukemia: A Pediatric Prospective
Authors: Cacace Fabiana , Iula Rossella , De Novellis Danilo , Caprioli Valeria , D’Amico Maria Rosaria , De Simone Giuseppina , Cuccurullo Rosanna , Wierda William G. , Mahadeo Kris Michael , Menna Giuseppe , Tambaro Francesco Paolo
Published: June 2022

Pediatric acute myeloid leukemia is a clonal disorder characterized by malignant transformation of the hematopoietic stem cell. The incidence and the outcome remain inferior when compared to pediatric ALL, although prognosis has improved in the last decades, with 80% overall survival rate reported in some studies. The standard therapeutic approach is a combined cytarabine and anthracycline-based regimen followed by consolidation with allogeneic stem cell transplantation (allo-SCT) for high-risk AML and allo-SCT for non-high-risk patients only in second complete remission after relapse. In the last decade, several drugs have been used in clinical trials to improve outcomes in pediatric AML treatment.
Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes
Authors: Eligini Sonia , Porro Benedetta , Werba José Pablo , Capra Nicolò , Genovese Stefano , Greco Arianna , Cavalca Viviana , Banfi Cristina
Published: June 2022

The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that increased in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications.
Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products
Authors: Hino Christopher , Pham Bryan , Park Daniel , Yang Chieh , Nguyen Michael H.K. , Kaur Simmer , Reeves Mark E. , Xu Yi , Nishino Kevin , Pu Lu , Kwon Sue Min , Zhong Jiang F. , Zhang Ke K. , Xie Linglin , Chong Esther G. , Chen Chien-Shing , Nguyen Vinh , Castillo Dan Ran , Cao Huynh
Published: June 2022

The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.
Terrain Perception Using Wearable Parrot-Inspired Companion Robot, KiliRo
Authors: Bharatharaj Jaishankar , Huang Loulin , Al-Jumaily Ahmed M. , Kutty Senthil Kumar Sasthan , Krägeloh Chris
Published: June 2022

Research indicates that deaths due to fall incidents are the second leading cause of unintentional injury deaths in the world. Death by fall due to a person texting or talking on mobile phones while walking, impaired vision, unexpected terrain changes, low balance, weakness, and chronic conditions has increased drastically over the past few decades. Particularly, unexpected terrain changes would many times lead to severe injuries and sometimes death even in healthy individuals. To tackle this problem, a warning system to alert the person of the imminent danger of a fall can be developed. This paper describes a solution for such a warning system used in our bio-inspired wearable pet robot, KiliRo. It is a terrain perception system used to classify the terrain based on visual features obtained from processing the images captured by a camera and notify the wearer of terrain changes while walking. The parrot-inspired KiliRo robot can twist its head and the camera up to 180 degrees to obtain visual feedback for classification. Feature extraction is followed by K-nearest neighbor for terrain classification. Experiments were conducted to establish the efficacy and validity of the proposed approach in classifying terrain changes. The results indicate an accuracy of over 95% across five terrain types, namely pedestrian pathway, road, grass, interior, and staircase.
Highly Sensitive Refractive Index Sensor Based on Polymer Bragg Grating: A Case Study on Extracellular Vesicles Detection
Authors: Saha Nabarun , Brunetti Giuseppe , Kumar Arun , Armenise Mario Nicola , Ciminelli Caterina
Published: June 2022

The measurement of small changes in the refractive index (RI) leads to a comprehensive analysis of different biochemical substances, paving the way to non-invasive and cost-effective medical diagnosis. In recent times, the liquid biopsy for cancer detection via extracellular vesicles (EV) in the bodily fluid is becoming very popular thanks to less invasiveness and stability. In this context, here we propose a highly sensitive RI sensor based on a compact high-index-coated polymer waveguide Bragg grating with a metal under cladding. Owing to the combined effect of a metal under cladding and a high-index coating, a significant enhancement in the RI sensitivity as well as the dynamic range has been observed. The proposed sensor has been analyzed by combining finite element method (FEM) and coupled-mode theory (CMT) approaches, demonstrating a sensitivity of 408–861 nm/RIU over a broad dynamic range of 1.32–1.44, and a strong evanescent field within a 150 nm proximity to the waveguide surface compliant with EV size. The aforementioned performance makes the proposed device suitable for performing real-time and on-chip diagnoses of cancer in the early stage.
EEG Classification of Normal and Alcoholic by Deep Learning
Authors: Li Houchi , Wu Lei
Published: June 2022

Alcohol dependence is a common mental disease worldwide. Excessive alcohol consumption may lead to alcoholism and many complications. In severe cases, it will lead to inhibition and paralysis of the centers of the respiratory and circulatory systems and even death. In addition, there is a lack of effective standard test procedures to detect alcoholism. EEG signals are data obtained by measuring brain changes in the cerebral cortex and can be used for the diagnosis of alcoholism. Existing diagnostic methods mainly employ machine learning techniques, which rely on human intervention to learn. In contrast, deep learning, as an end-to-end learning method, can automatically extract EEG signal features, which is more convenient. Nonetheless, there are few studies on the classification of alcohol’s EEG signals using deep learning models. Therefore, in this paper, a new deep learning method is proposed to automatically extract and classify EEG’s features. The method first adopts a multilayer discrete wavelet transform to denoise the input data. Then, the denoised data are used as input, and a convolutional neural network and bidirectional long short-term memory network are used for feature extraction. Finally, alcohol EEG signal classification is performed. The experimental results show that the method proposed in this study can be utilized to effectively diagnose patients with alcoholism, achieving a diagnostic accuracy of 99.32%, which is better than most current algorithms.
A Comparative Study of Explicit and Stable Time Integration Schemes for Heat Conduction in an Insulated Wall
Authors: Kareem Jalghaf Humam , Omle Issa , Kovács Endre
Published: June 2022

Calculating heat transfer in building components is an important and nontrivial task. Thus, in this work, we extensively examined 13 numerical methods to solve the linear heat conduction equation in building walls. Eight of the used methods are recently invented explicit algorithms which are unconditionally stable. First, we performed verification tests in a 2D case by comparing them to analytical solutions, using equidistant and non-equidistant grids. Then we tested them on real-life applications in the case of one-layer (brick) and two-layer (brick and insulator) walls to determine how the errors depend on the real properties of the materials, the mesh type, and the time step size. We applied space-dependent boundary conditions on the brick side and time-dependent boundary conditions on the insulation side. The results show that the best algorithm is usually the original odd-even hopscotch method for uniform cases and the leapfrog-hopscotch algorithm for non-uniform cases.
Creative Thinking in the Architecture Design Studio: Bibliometric Analysis and Literature Review
Authors: Park Eun Joo , Lee Sanghee
Published: June 2022

It is increasingly important for researchers and educators to find effective ways to stimulate students’ creativity. In design education, the specificity of design, defined as open-ended problems and ill-defined problems, provides a special opportunity to improve creativity. Nevertheless, design education itself encounters other issues concerning creativity, such as not specifying in detail what creative design pedagogy should be. Thus, a comprehensive review of existing studies is needed to guide research in this field better. We used bibliometric analysis to provide information on literature statistics of the 658 articles published in design research–related journals between 1982 and 2022. An in-depth review of the 36 selected articles revealed the existing research on the design studio to investigate creativity from three perspectives: (1) creativity criteria and evaluation, (2) idea generation and development, and (3) pedagogy in the design studio. This study provides a roadmap for global educators and researchers focusing on pedagogy that enhances students’ creativity in the design studio.
Artificial Neural Network for Predicting Building Energy Performance: A Surrogate Energy Retrofits Decision Support Framework
Authors: Zhang Haonan , Feng Haibo , Hewage Kasun , Arashpour Mehrdad
Published: June 2022

Assessing the energy performance of existing residential buildings (ERB) has been identified as key to improving building energy efficiency and reducing associated greenhouse gas emissions in Canada. However, identifying optimal retrofit packages requires a significant amount of knowledge of building energy modelling, and it is a time-consuming and laborious process. This paper proposed a data-driven framework that combines machine learning, multi-objective optimization, and multi-criteria decision-making techniques to evaluate the energy performance of ERB and thereby formulate optimal retrofit plans. First, an artificial neural network (ANN) was developed to predict the energy performance of a wide range of retrofit packages. A genetic algorithm was employed to determine the best structure and hyperparameters of the ANN model. Then, the energy consumption results were integrated with environmental and economic impact data to evaluate the environmental and economic performance of retrofit packages and thereby identify Pareto optimal solutions. Finally, a multi-criteria decision-making method was used to select the best retrofit packages among the optimal solutions. The proposed framework was validated using data on a typical residential building in British Columbia, Canada. The results indicated that this framework could effectively predict building energy performance and help decision-makers to make an optimal decision when choosing retrofit packages.
Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study
Authors: Chen Chun-Chao , Wu Chia-Hsien , Lin Cheng-Hsin , Chiu Chun-Chih , Yang Tsung-Yeh , Lei Meng-Huan , Yeh Hsien-Tang , Jian William , Fang Yu-Ann , Hao Wen-Rui , Liu Ju-Chi
Published: June 2022

Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan’s National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38–0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66–1.25), 0.49 (0.34–0.71), and 0.25 (0.17–0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.
Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms
Authors: Godwin Colin , Rodríguez-Arbolí Eduardo , Othus Megan , Halpern Anna , Appelbaum Jacob , Percival Mary-Elizabeth , Hendrie Paul , Oehler Vivian , Keel Siobán , Abkowitz Janis , Cooper Jason , Cassaday Ryan , Estey Elihu , Walter Roland
Published: June 2022

Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Sixty-six patients with a median age of 65 (range: 19–80) years were enrolled. Cohorts of six and twelve patients were treated in phase 1 with one dose of GO or three doses of GO (GO3) at 3 mg/m2 per dose. Since a maximum-tolerated dose was not reached, the recommended phase 2 dose (RP2D) was declared to be GO3. At RP2D, 52/60 (87%) patients achieved a complete remission (CR)/CR with incomplete hematologic recovery (CRi), 45/52 (87%) without flow cytometric measurable residual disease (MRD). Eight-week mortality was 0%. Six- and twelve-month event-free survival (EFS) were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M/GO3 was associated with better survival in patients with favorable-risk disease (EFS: p = 0.007; OS: p = 0.030). These data indicate that CLAG-M/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm.
A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy
Authors: de la Fuente Ana , Santisteban Marta , Lupón Josep , Aramendía José , Díaz Agnes , Santaballa Ana , Hernándiz Amparo , Sepúlveda Pilar , Cediel Germán , López Begoña , Picazo José , Mazo Manuel , Rábago Gregorio , Gavira Juan , García-Bolao Ignacio , Díez Javier , González Arantxa , Bayés-Genís Antoni , Ravassa Susana
Published: June 2022

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.
Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review
Authors: Ramai Daryl , Deliwala Smit S. , Chandan Saurabh , Lester Janice , Singh Jameel , Samanta Jayanta , di Nunzio Sara , Perversi Fabio , Cappellini Francesca , Shah Aashni , Ghidini Michele , Sacco Rodolfo , Facciorusso Antonio , Giacomelli Luca
Published: June 2022

Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.
Progress in Catalytic Conversion of Renewable Chitin Biomass to Furan-Derived Platform Compounds
Authors: Xu Benjing , Du Ziting , Dai Jinhang , Yang Ronghe , Yang Delong , Gu Xingxing , Li Ning , Li Fukun
Published: June 2022

Chitin is one of the most abundant biopolymers on Earth but under-utilized. The effective conversion of chitin biomass to useful chemicals is a promising strategy to make full use of chitin. Among chitin-derived compounds, some furan derivatives, typically 5-hydroxymethylfurfural and 3-acetamido-5-acetylfuran, have shown great potential as platform compounds in future industries. In this review, different catalytic systems for the synthesis of nitrogen-free 5-hydroxymethylfurfural and nitrogen-containing 3-acetamido-5-acetylfuran from chitin or its derivatives are summarized comparatively. Some efficient technologies for enhancing chitin biomass conversion have been introduced. Last but not least, future challenges are discussed to enable the production of valuable compounds from chitin biomass via greener processes.
T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies
Authors: Pulvirenti Federica , Di Cecca Stefano , Sinibaldi Matilde , Piano Mortari Eva , Terreri Sara , Albano Christian , Guercio Marika , Sculco Eleonora , Milito Cinzia , Ferrari Simona , Locatelli Franco , Quintarelli Concetta , Carsetti Rita , Quinti Isabella
Published: June 2022

Following the third booster dose of the mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against the virus spike protein. The T-cell abnormalities associated with the absence of antibodies are still a matter of investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L and cytokine expression, and Spike-specific specific T-cells responses were evaluated in 47 CVID and 26 healthy donors after three doses of BNT162b2 vaccine. Testing was performed two weeks after the third vaccine dose. Thirty-six percent of the patients did not produce anti-SARS-CoV-2 IgG or IgA antibodies. Non responder patients had lower peripheral blood lymphocyte counts, circulating naïve and central memory T-cells, low CD40L expression on the CD4+CD45+RO+ and CD8+CD45+RO+ T-cells, high frequencies of TNFα and IFNγ expressing CD8+ T-cells, and defective release of IFNγ and TNFα following stimulation with Spike peptides. Non responders had a more complex disease phenotype, with higher frequencies of structural lung damage and autoimmunity, especially autoimmune cytopenia. Thirty-five percent of them developed a SARS-CoV-2 infection after immunization in comparison to twenty percent of CVID who responded to immunization with antibodies production. CVID-associated T cell abnormalities contributed to the absence of SARS-CoV-2 specific antibodies after full immunization.
Genetically Encoded ATP Biosensors for Direct Monitoring of Cellular ATP Dynamics
Authors: White Donnell , Yang Qinglin
Published: June 2022

Adenosine 5′-triphosphate, or ATP, is the primary molecule for storing and transferring energy in cells. ATP is mainly produced via oxidative phosphorylation in mitochondria, and to a lesser extent, via glycolysis in the cytosol. In general, cytosolic glycolysis is the primary ATP producer in proliferative cells or cells subjected to hypoxia. On the other hand, mitochondria produce over 90% of cellular ATP in differentiated cells under normoxic conditions. Under pathological conditions, ATP demand rises to meet the needs of biosynthesis for cellular repair, signaling transduction for stress responses, and biochemical processes. These changes affect how mitochondria and cytosolic glycolysis function and communicate. Mitochondria undergo remodeling to adapt to the imbalanced demand and supply of ATP. Otherwise, a severe ATP deficit will impair cellular function and eventually cause cell death. It is suggested that ATP from different cellular compartments can dynamically communicate and coordinate to adapt to the needs in each cellular compartment. Thus, a better understanding of ATP dynamics is crucial to revealing the differences in cellular metabolic processes across various cell types and conditions. This requires innovative methodologies to record real-time spatiotemporal ATP changes in subcellular regions of living cells. Over the recent decades, numerous methods have been developed and utilized to accomplish this task. However, this is not an easy feat. This review evaluates innovative genetically encoded biosensors available for visualizing ATP in living cells, their potential use in the setting of human disease, and identifies where we could improve and expand our abilities.
Delineation of Pathogenomic Insights of Breast Cancer in Young Women
Authors: Paul Aswathy Mary , George Bijesh , Saini Sunil , Pillai Madhavan Radhakrishna , Toi Masakazu , Costa Luis , Kumar Rakesh
Published: June 2022

The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment.
Fabrication and Magneto-Structural Properties of Co2-Based Heusler Alloy Glass-Coated Microwires with High Curie Temperature
Authors: Salaheldeen Mohamed , Garcia-Gomez Alfonso , Ipatov Mihail , Corte-Leon Paula , Zhukova Valentina , Blanco Juan Maria , Zhukov Arcady
Published: June 2022

In this work, we were able to produce Co2FeSi Heusler alloy glass-covered microwires with a metallic nucleus diameter of about 4.4 µm and total sample diameter of about 17.6 μm by the Taylor–Ulitovsky Technique. This low cost and single step fabrication process allowed the preparation of up to kilometers long glass-coated microwires starting from a few grams of high purity inexpensive elements (Co, Fe and Si), for a wide range of applications. From the X-ray diffraction, XRD, analysis of the metallic nucleus, it was shown that the structure consists of a mixture of crystalline and amorphous phases. The single and wide crystalline peak was attributed to a L21 crystalline structure (5.640 Å), with a possible B2 disorder. In addition, nanocrystalline structure with an average grain size, Dg = 17.8 nm, and crystalline phase content of about 52% was obtained. The magnetic measurements indicated a well-defined magnetic anisotropy for all ranges of temperature. Moreover, soft magnetic behavior was observed for the temperature measuring range of 5–1000 K. Strong dependence of the magnetic properties on the applied magnetic field and temperature was observed. Zero field cooling and field cooling magnetization curves showed large irreversibility magnetic behavior with a blocking temperature (TB = 205 K). The in-plane magnetization remanence and coercivity showed quite different behavior with temperature, due to the existence of different magnetic phases induced from the internal stress created by the glass-coated layer. Moreover, a high Curie temperature was reported (Tc ≈ 1059 K), which predisposes this material to being a suitable candidate for high temperature spintronic applications.
Congenital Heart Disease: Growth Evaluation and Sport Activity in a Paediatric Population
Authors: Zoller Thomas , Prioli Maria Antonia , Clemente Maria , Pilati Mara , Sandrini Camilla , Luciani Giovanni Battista , Deganello Saccomani Marco , Ficial Benjamim , Gaffuri Marcella , Piacentini Giorgio , Calciano Lucia , Pietrobelli Angelo
Published: June 2022

(1) Objective: To evaluate: (i) the associations of age and disease severity with anthropometric indices and weight status, (ii) the difference in the frequency of sports activity among different levels of disease severity in paediatric patients with congenital heart disease (CHD). (2) Methods: Clinical data of Caucasian children (aged 2–18 years) diagnosed with CHD (2005–2018) were retrospectively collected from the electronic register of outpatient visits. Of the 475 children with CHD, 368 children and their 1690 complete anthropometric measurements were eligible for inclusion in our analysis. (3) Results: Significant increase with age was observed for weight z-score [beta (95%CI): 0.03 (0.02, 0.05) for one-unit of age] and BMI z-score [0.06 (0.03, 0.08)] but not for height z-score. The probability of being underweight and overweight/obese increased and decreased with disease severity, respectively. The obesity probability of patients with mild CHD (0.06 [95%CI: 0.03, 0.08]) was not statistically distinguishable from that of patients with moderate CHD (0.03 [95%CI: 0.02, 0.05]), whereas it was lower in patients with severe CHD (0.004 [95%CI: 0.0, 0.009]). No obese patients with a univentricular heart defect were observed. Days spent in sport activities were equal to 1.9 [95%CI: 1.6, 2.2] days/week, 1.9 [1.5, 2.2], 1.4 [1.1, 1.7] and 0.7 [0.1, 1.3] in patients with mild, moderate, severe and univentricular CHD, respectively. (4) Conclusions: The risk of being overweight and obese should not be underestimated in paediatric patients diagnosed with CHD, especially in children with mild or moderate heart defects. It could be prevented or reduced by promoting a healthy lifestyle.
Child Abuse and Neglect Awareness among Medical Students
Authors: Al-Qahtani Mohammad H. , Almanamin Haitham H. , Alasiri Ahmed M. , Alqudaihi Mohammed H. , AlSaffar Mohammed H. , Yousef Abdullah A. , Awary Bassam H. , Albuali Waleed H.
Published: June 2022

Physical, emotional, and sexual abuse and various forms of neglect of children have been encountered more frequently by healthcare providers, particularly physicians. However, mismanagement of child abuse and neglect (CAN) due to a lack of awareness of it can lead to substantial and serious consequences. This study primarily aimed to evaluate the awareness of CAN among medical students and compare it between preclinical and clinical males and females in Imam Abdulrahman Bin Faisal University in Dammam, Saudi Arabia. A cross-sectional study using a self-reported-based questionnaire was carried out to study child abuse and neglect awareness and compare preclinical and clinical male versus female medical students during the first semester in 2021/2022. The majority of the participants were aware of CAN (90.6%), agreed that CAN exists locally (96.6%), believed that CAN is important in the medical field (96.3%), and expressed the important role of physicians in participating in the management of CAN (84.3%). Some students did not know about the legislation of CAN in Saudi Arabia (15%). The results show a lack of exposure to real CAN cases (80.3%) and the need for more formal education (70.3%). In general, the students were comparable, but there were significant differences showing more awareness in female students compared to males and, similarly, more awareness in clinical-year students. Both clinical and preclinical medical students were aware of CAN, with some concerns regarding their competency in dealing with CAN. CAN should be given more weight in the medical school curriculum.
The Phenotypical Profile and Outcomes of Neonates with Congenital Tracheoesophageal Fistula Associated with Congenital Cardiac Anomalies Presenting for Surgery
Authors: Hoyi Nomvuyo , Mogane Palesa , Madima Nthatheni , Motshabi Palesa
Published: June 2022

(1) Background: Neonates born with oesophageal atresia and/or tracheooesophageal fistula (OA/TOF) are usually born with a multitude of other congenital anomalies, which may affect their anaesthetic care and survival to hospital discharge. We reviewed the profile and outcome of neonates with OA/TOF and associated congenital cardiac anomalies presenting for surgery at an academic hospital in South Africa. (2) Methods: A retrospective, cross-sectional analysis of all medical records of neonates who had undergone surgical repair of OA/TOF was conducted at an academic hospital between January 2015 and December 2019. Descriptive statistics were used to report the data. Comparisons in perioperative events and outcomes between those with cardiac lesions and those without were done. (3) Results: Neonates presenting for OA/TOF repair with congenital cardiac defects had an incidence of 62 [95% CI 38.5–99.8] per 1000 days since birth. In total, 45.9% had associated cardiac anomalies, with PDA and ASD as the most prevalent lesions. There were statistically significant differences in intraoperative adverse events seen in neonates with congenital cardiac lesions as compared to those without. (4) Conclusion: Despite advances in neonatal critical care and anaesthetic and surgical techniques, OA/TOF associated with congenital cardiac anomalies is still associated with high mortality rates in developing countries.
Fetal and Newborn Management of Cloacal Malformations
Authors: Jacobs Shimon E. , Tiusaba Laura , Al-Shamaileh Tamador , Bokova Elizaveta , Russell Teresa L. , Ho Christina P. , Varda Briony K. , Pohl Hans G. , Mayhew Allison C. , Gomez-Lobo Veronica , Feng Christina , Badillo Andrea T. , Levitt Marc A.
Published: June 2022

Cloaca is a rare, complex malformation encompassing the genitourinary and anorectal tract of the female in which these tracts fail to separate in utero, resulting in a single perineal orifice. Prenatal sonography detects a few cases with findings such as renal and urinary tract malformations, intraluminal calcifications, dilated bowel, ambiguous genitalia, a cystic pelvic mass, or identification of other associated anomalies prompting further imaging. Multi-disciplinary collaboration between neonatology, pediatric surgery, urology, and gynecology is paramount to achieving safe outcomes. Perinatal evaluation and management may include treatment of cardiopulmonary and renal anomalies, administration of prophylactic antibiotics, ensuring egress of urine and evaluation of hydronephrosis, drainage of a hydrocolpos, and creation of a colostomy for stool diversion. Additional imaging of the spinal cord and sacrum are obtained to plan possible neurosurgical intervention as well as prognostication of future bladder and bowel control. Endoscopic evaluation and cloacagram, followed by primary reconstruction, are performed by a multidisciplinary team outside of the neonatal period. Long-term multidisciplinary follow-up is essential given the increased rates of renal disease, neuropathic bladder, tethered cord syndrome, and stooling issues. Patients and families will also require support through the functional and psychosocial changes in puberty, adolescence, and young adulthood.
Relative Age Effect in Attention Deficit/Hyperactivity Disorder at Various Stages of the Medicalization Process
Authors: Brault Marie-Christine , Degroote Emma , Jean Mireille , Van Houtte Mieke
Published: June 2022

Diagnosis and pharmacological treatment of ADHD are more common among the youngest children in a classroom, born in the months immediately preceding the school entry cutoff date. The mechanisms behind this phenomenon, called the relative age effect (RAE), are not yet well understood. Nearly all hypotheses involve the school system, various teachers’ actions, and concern children’s immaturity. However, most previous studies have been based on reports of health professionals’ diagnoses and prescriptions found in official databases rather than on reports of teachers’ behavior identification or suspicion of ADHD, despite their being at the first stages of the medicalization process. Our study overcomes this limitation by using reports of parents’ and teachers’ behavior identification or suspicion of ADHD within a three-level multilevel survey design, comprising 1294 children, 130 teachers, and 17 elementary public schools. The goal of our study was to investigate whether RAE stems (1) from adults’ judgement of the child’s expression of immaturity or (2) from the consequences associated with the child’s double burden of being immature and exhibiting ADHD behaviors. Our multilevel analyses put forward the first hypothesis only, supporting the medicalization of immaturity. RAE in ADHD seems mostly initiated by teachers’ pre-diagnostic actions toward younger children.
Pattern Recognition for Human Diseases Classification in Spectral Analysis
Authors: Hasbi Nur Hasshima , Bade Abdullah , Chee Fuei Pien , Rumaling Muhammad Izzuddin
Published: June 2022

Pattern recognition is a multidisciplinary area that received more scientific attraction during this period of rapid technological innovation. Today, many real issues and scenarios require pattern recognition to aid in the faster resolution of complicated problems, particularly those that cannot be solved using traditional human heuristics. One common problem in pattern recognition is dealing with multidimensional data, which is prominent in studies involving spectral data such as ultraviolet-visible (UV/Vis), infrared (IR), and Raman spectroscopy data. UV/Vis, IR, and Raman spectroscopy are well-known spectroscopic methods that are used to determine the atomic or molecular structure of a sample in various fields. Typically, pattern recognition consists of two components: exploratory data analysis and classification method. Exploratory data analysis is an approach that involves detecting anomalies in data, extracting essential variables, and revealing the data’s underlying structure. On the other hand, classification methods are techniques or algorithms used to group samples into a predetermined category. This article discusses the fundamental assumptions, benefits, and limitations of some well-known pattern recognition algorithms including Principal Component Analysis (PCA), Kernel PCA, Successive Projection Algorithm (SPA), Genetic Algorithm (GA), Partial Least Square Regression (PLS-R), Linear Discriminant Analysis (LDA), K-Nearest Neighbors (KNN), Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), Partial Least Square-Discriminant Analysis (PLS-DA) and Artificial Neural Network (ANN). The use of UV/Vis, IR, and Raman spectroscopy for disease classification is also highlighted. To conclude, many pattern recognition algorithms have the potential to overcome each of their distinct limits, and there is also the option of combining all of these algorithms to create an ensemble of methods.
Plant and Herbal Extracts as Ingredients of Topical Agents in the Prevention and Treatment Radiodermatitis: A Systematic Literature Review
Authors: Kulawik-Pióro Agnieszka , Goździcka Weronika Joanna
Published: June 2022

Background: The use of herbal extracts as the source of antioxidant substances capable of neutralizing free radicals and providing protection from ionizing radiation appears to be an alternative therapy for radiodermatitis. As concerns the prevention and treatment of side effects, a lot of recommendations are based on proper experience of radiotherapy centers. We summarize recent research aiming at reducing radiation-induced skin injuries by use of proper skin care, using topical preparations with herbal extracts including onco-cosmetics. Methods: This article is limited to a critical analysis of scientific and professional literature. It concerns preparations in different physicochemical forms, e.g., gels, emulsions, ointments. We stress the connection between the type of applied skin care (type of preparation, its composition, the dose), the properties of the herbal extract and the evaluation of its efficiency in preventing and treating radiation reaction on skin. Conclusions: Herbal extracts can be added to recipes because they are part of a category of cosmeceutical supplements and can be introduced into preparations without prescription. The effectiveness evaluation for herbal extracts in radiotherapy is not an easy task since there are no strict guidelines. Studies should be preceded by the analysis of herbal extracts and recipe in terms of physicochemical, dermatological and performance characteristics.
Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis
Authors: Yu Tsung-Ying , Jhou Hong-Jie , Chen Po-Huang , Lee Cho-Hao
Published: June 2022

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and safety of lenalidomide maintenance are still debated. Randomized controlled trials published before March 2022 were retrieved from databases. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Trial sequential analysis examined analytical power in primary outcomes. Secondary outcomes were Grade 3–4 neutropenia, treatment discontinuation (TD), serious adverse events (SAE), and fatal adverse events (FAE). Hazard (HR) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Four articles (733 patients) met the selection criteria. Lenalidomide maintenance was associated with a statistically significant effect in prolonging PFS (HR, 0.43; 95% CI, 0.28–0.68; I2 = 57%) and higher proportion of SAE (OR 4.64; 95% CI 2.96–7.26; I2 = 0%) and exhibited no difference in OS (HR, 0.62; 95% CI, 0.29–1.30; I2 = 52%) observation/placebo. It showed no significant difference compared with observation/placebo regarding Grade 3–4 neutropenia (OR 2.30; 95% CI 0.84–6.28; I2 = 81%), TD (OR 0.76; 95% CI 0.29–1.99; I2 = 84%), and FAE (OR 0.86; 95% CI 0.28–2.63; I2 = 0%). Lenalidomide maintenance can prolong PFS in CLL. Further studies should verify its effect on OS.
Temporal Partitioning of Fungal Sporophores in a Temperate Deciduous Broad-Leaved Forest
Authors: Zhou Ziyu , Xiao Man , Wang Senlin , Wang Xueying , Li Wang , Chen Yun , Yuan Zhiliang , Guo Erhui
Published: June 2022

The temporal partitioning hypothesis refers to the promotion of stable species’ coexistence by reducing the likelihood of competitive exclusion, such as when species are active at different months of the year. However, the studies confirming the mechanisms of species’ coexistence focus on spatial scale, and temporal partitioning hypothesis for species’ coexistence remains underexplored. Fungal sporophores that are sensitive to seasonality change are ideal candidates for studying the role of temporal differentiation hypothesis in species’ coexistence. In this study, a field survey of fungal sporocarps was conducted from May to October, and the entity and abundance of different species of fungal sporocarps in a 5-hectare forest dynamic plot in a temperate, deciduous broad-leaved forest were recorded. The results showed that the emergence of fungal sporocarps based on month was highly specialized and uneven. The torus-translation test showed that 56 species exhibited ecological habitat preferences for different months (47/100, 47%). The distribution of soil fungal sporocarps (35/75, 46.67%) based on months showed higher specialization compared with that of rotten-wood fungal sporocarps (9/22, 40.90%). The findings suggest the importance of temporal partitioning in maintaining local diversity in the fungal community.