bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry
Authors: Merz Maximilian , Goldschmidt Hartmut , Hari Parameswaran , Agha Mounzer , Diels Joris , Ghilotti Francesca , Perualila Nolen J. , Cabrieto Jedelyn , Haefliger Benjamin , Sliwka Henrik , Schecter Jordan M. , Jackson Carolyn C. , Olyslager Yunsi , Akram Muhammad , Nesheiwat Tonia , Kellermann Lenka , Jagannath Sundar
Published: November 2021

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.
Stromal Cells Promote Matrix Deposition, Remodelling and an Immunosuppressive Tumour Microenvironment in a 3D Model of Colon Cancer
Authors: Leonard Niamh A. , Reidy Eileen , Thompson Kerry , McDermott Emma , Peerani Eleonora , Tomas Bort Elena , Balkwill Frances R. , Loessner Daniela , Ryan Aideen E.
Published: November 2021

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops in a complex tumour microenvironment (TME) with both mesenchymal stromal cells (MSCs) and immune infiltrate, shown to alter disease progression and treatment response. We hypothesised that an accessible, affordable model of CRC that combines multiple cell types will improve research translation to the clinic and enable the identification of novel therapeutic targets. A viable gelatine-methacrloyl-based hydrogel culture system that incorporates CRC cells with MSCs and a monocyte cell line was developed. Gels were analysed on day 10 by PCR, cytokine array, microscopy and flow cytometry. The addition of stromal cells increased transcription of matrix remodelling proteins FN1 and MMP9, induced release of tumour-promoting immune molecules MIF, Serpin E1, CXCL1, IL-8 and CXCL12 and altered cancer cell expression of immunotherapeutic targets EGFR, CD47 and PD-L1. Treatment with PD153035, an EGFR inhibitor, revealed altered CRC expression of PD-L1 but only in gels lacking MSCs. We established a viable 3D model of CRC that combined cancer cells, MSCs and monocytic cells that can be used to research the role the stroma plays in the TME, identify novel therapeutic targets and improve the transitional efficacy of therapies.
Integrin αvβ6 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions
Authors: Huisman Bertine W. , Cankat Merve , Bosse Tjalling , Vahrmeijer Alexander L. , Rissmann Robert , Burggraaf Jacobus , Sier Cornelis F. M. , van Poelgeest Mariette I. E.
Published: November 2021

Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation. To evaluate potential targets for FGS in VSCC, immunohistochemistry was performed on paraffin-embedded premalignant (high grade squamous intraepithelial lesion and differentiated vulvar intraepithelial neoplasia) and VSCC (human papillomavirus (HPV)-dependent and -independent) tissue sections with healthy vulvar skin as controls. Sections were stained for integrin αvβ6, CAIX, CD44v6, EGFR, EpCAM, FRα, MRP1, MUC1 and uPAR. The expression of each marker was quantified using digital image analysis. H-scores were calculated and percentages positive cells, expression pattern, and biomarker localization were assessed. In addition, tumor-to-background ratios were established, which were highest for (pre)malignant vulvar tissues stained for integrin αvβ6. In conclusion, integrin αvβ6 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared to surrounding healthy tissue in immunohistochemically stained tissue sections. The use of an αvβ6 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.
Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review
Authors: Orlandella Francesca Maria , Auletta Luigi , Greco Adelaide , Zannetti Antonella , Salvatore Giuliana
Published: November 2021

Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.
EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 3)
Authors: Zanelli Magda , Sanguedolce Francesca , Palicelli Andrea , Zizzo Maurizio , Martino Giovanni , Caprera Cecilia , Fragliasso Valentina , Soriano Alessandra , Gozzi Fabrizio , Cimino Luca , Masia Francesco , Moretti Marina , Foroni Moira , De Marco Loredana , Pellegrini David , De Raeve Hendrik , Ricci Stefano , Tamagnini Ione , Tafuni Alessandro , Cavazza Alberto , Merli Francesco , Pileri Stefano A. , Ascani Stefano
Published: November 2021

EBV is the first known oncogenic virus involved in the development of several tumors. The majority of the global population are infected with the virus early in life and the virus persists throughout life, in a latent stage, and usually within B lymphocytes. Despite the worldwide diffusion of EBV infection, EBV-associated diseases develop in only in a small subset of individuals often when conditions of immunosuppression disrupt the balance between the infection and host immune system. EBV-driven lymphoid proliferations are either of B-cell or T/NK-cell origin, and range from disorders with an indolent behavior to aggressive lymphomas. In this review, which is divided in three parts, we provide an update of EBV-associated lymphoid disorders developing in the gastrointestinal tract, often representing a challenging diagnostic and therapeutic issue. Our aim is to provide a practical diagnostic approach to clinicians and pathologists who face this complex spectrum of disorders in their daily practice. In this part of the review, the chronic active EBV infection of T-cell and NK-cell type, its systemic form; extranodal NK/T-cell lymphoma, nasal type and post-transplant lymphoproliferative disorders are discussed.
Facile Synthesis of Iron-Based MOFs MIL-100(Fe) as Heterogeneous Catalyst in Kabachnick Reaction
Authors: Elharony Noura Elsayed , El Sayed Ibrahim El Tantawy , Al-Sehemi Abdullah G. , Al-Ghamdi Ahmed A. , Abou-Elyazed Ahmed S.
Published: November 2021

An effective technique was proposed for the synthesis of novel α-aminophosphonates: a three-component one-pot condensation reaction of aniline, aromatic aldehydes, and triphenyl phosphite in the presence of (MIL-100(Fe)) as a heterogeneous catalyst. Initially, MIL-100(Fe) was synthesized using H3BTC and ferric nitrate at low temperature and atmospheric pressure. Further, MIL-100(Fe) was characterized using various techniques such as XRD, BET surface area, scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), and thermogravimetric analysis (TGA). Herein, MIL-100(Fe) showed exceptional catalytic performance for the synthesis of α-aminophosphonate and its derivatives compared with conventional solid catalysts, and even homogeneous catalysts. The study demonstrated that MIL-100(Fe) is an ecofriendly and easily recyclable heterogeneous catalyst in Kabachnick reactions for α-aminophosphonate synthesis, with high yield (98%) and turnover frequency (TOF ~ 3.60 min−1) at room temperature and a short reaction time (30 min).
Extracellular Matrix Oxidised by the Granulocyte Oxidants Hypochlorous and Hypobromous Acid Reduces Lung Fibroblast Adhesion and Proliferation In Vitro
Authors: Papanicolaou Michael , He Patrick , Rutting Sandra , Ammit Alaina , Xenaki Dikaia , van Reyk David , Oliver Brian G.
Published: November 2021

Chronic airway inflammation and oxidative stress play crucial roles in the pathogenesis of chronic inflammatory lung diseases, with airway inflammation being a key driving mechanism of oxidative stress in the lungs. Inflammatory responses in the lungs activate neutrophils and/or eosinophils, leading to the generation of hypohalous acids (HOX). These HOX oxidants can damage the extracellular matrix (ECM) structure and may influence cell–ECM interactions. The ECM of the lung provides structural, mechanical, and biochemical support for cells and determines the airway structure. One of the critical cells in chronic respiratory disease is the fibroblast. Thus, we hypothesised that primary human lung fibroblasts (PHLF) exposed to an oxidised cell-derived ECM will result in functional changes to the PHLF. Here, we show that PHLF adhesion, proliferation, and inflammatory cytokine secretion is affected by exposure to HOX-induced oxidisation of the cell-derived ECM. Furthermore, we investigated the impact on fibroblast function from the presence of haloamines in the ECM. Haloamines are chemical by-products of HOX and, like the HOX, haloamines can also modify the ECM. In conclusion, this study revealed that oxidising the cell-derived ECM might contribute to functional changes in PHLF, a key mechanism behind the pathogenesis of inflammatory lung diseases.
Texture of the Freshwater Shells from the Unionidae Family Collected in the Czech Republic Investigated by X-ray and Neutron Diffraction
Authors: Kučeráková Monika , Rohlíček Jan , Vratislav Stanislav , Jarošová Markéta , Kalvoda Ladislav , Nikolayev Dmitry , Lychagina Tatiana , Douda Karel
Published: November 2021

Bivalve shells exhibit extreme mechanical resistance despite using a minimal amount of material. The shells thus represent an inspiration and a source of information for environmental, geological, and engineering sciences. In this study, two species of freshwater shells from the Unionidae family, collected in the Czech Luznice River, were investigated with respect to their crystallographic preferred orientation by means of X-ray and neutron diffraction. The observed texture was found to be of a strongly uniaxial type, with the strength increasing along the shell growth direction. The c-axis of aragonite does not change during growth and its alignment remains perpendicular to the outer surface of the shell
Biomarkers in the Light of the Etiopathology of IC/BPS
Authors: Neuhaus Jochen , Berndt-Paetz Mandy , Gonsior Andreas
Published: November 2021

In this review, we focused on putatively interesting biomarkers of interstitial cystitis/bladder pain syndrome (IC/BPS) in relation to the etiopathology of this disease. Since its etiopathology is still under discussion, the development of novel biomarkers is critical for the correct classification of the patients in order to open personalized treatment options, on the one hand, and to separate true IC/BPS from the numerous confusable diseases with comparable symptom spectra on the other hand. There is growing evidence supporting the notion that the classical or Hunner-type IC (HIC) and the non-Hunner-type IC (NHIC) are different diseases with different etiopathologies and different pathophysiology at the full-blown state. While genetic alterations indicate close relationship to allergic and autoimmune diseases, at present, the genetic origin of IC/BPS could be identified. Disturbed angiogenesis and impairment of the microvessels could be linked to altered humoral signaling cascades leading to enhanced VEGF levels which in turn could enhance leucocyte and mast cell invasion. Recurrent or chronic urinary tract infection has been speculated to promote IC/BPS. New findings show that occult virus infections occurred in most IC/BPS patients and that the urinary microbiome was altered, supporting the hypothesis of infections as major players in IC/BPS. Environmental and nutritional factors may also influence IC/BPS, at least at a late state (e.g., cigarette smoking can enhance IC/BPS symptoms). The damage of the urothelial barrier could possibly be the result of many different causality chains and mark the final state of IC/BPS, the causes of this development having been introduced years ago. We conclude that the etiopathology of IC/BPS is complex, involving regulatory mechanisms at various levels. However, using novel molecular biologic techniques promise more sophisticated analysis of this pathophysiological network, resulting in a constantly improvement of our understanding of IC/BPS and related diseases.
Prenatal Diagnosis of Clubfoot: Where Are We Now? Systematic Review and Meta-Analysis
Authors: Ruzzini Laura , De Salvatore Sergio , Longo Umile Giuseppe , Marino Martina , Greco Alessandra , Piergentili Ilaria , Costici Pier Francesco , Denaro Vincenzo
Published: November 2021

The primary methods for prenatal diagnosis of Clubfoot are ultrasound (US) and magnetic resonance imaging (MRI). An ultrasound is performed between the 1st trimester and the 28th week of pregnancy and it is reported to be used as a diagnostic method alone or in combination with MRI. So far, an international consensus on the most effective screening method has not been reached. This systematic review and meta-analysis were performed to establish the most effective and reliable exam for prenatal diagnosis of Clubfoot. The literature search was conducted using a PIOS-approach from May 2021 to June 2021. Studies reporting cases of prenatal diagnosis of Clubfoot made through US and MRI conducted from January 2010 to June 2021 were included in the study and reviewed by 2 authors. The 23 selected studies included 2318 patients. A total of 11 of the studies included details on the accuracy, while the rest were used to obtain information about the primary methodology utilized. In all the selected studies, US was used as the primary diagnostic instrument. Thirteen of the studies used the US exclusively, while three used MRI in addition to US and seven performed karyotyping after US diagnosis. The US has been shown to be the instrument of choice for the prenatal diagnosis of Clubfoot. International guidelines for an ultrasonography classification of congenital clubfoot are required to reduce the inter-variability accuracy of this procedure.
Design of A Ka-Band 3D-Printed Dual-Polarization Magnetoelectric Dipole Antenna Array with Low Sidelobe
Authors: Wang Yikun , Tan Wenhao , Zhu Kaiqiang , Luo Hao , Zhao Guoqiang , Sun Houjun
Published: November 2021

A Ka-band dual-polarization magnetoelectric (ME) dipole antenna array based on three-dimensional (3D)-printed technology with low sidelobe level (SLL) is proposed in this paper. The metal posts and cross-slots are explored to build a novel subarray with 2 × 2-unit ME-dipoles as the basic element. Creatively, a square waveguide to cross-slots transition with a pyramid horn cavity structure is investigated to feed the ME-dipole subarray. Furthermore, two types of power-tapering corporate-feed networks with laminated structures are used to design an 8 × 8-unit low-SLL array. The fabricated array has a relative bandwidth (VSWR < 2) of 14.3% and 17.1%, with a realized gain higher than 25.8 dBi and 26.1 dBi for the H-pol. and V-pol., respectively. The maximum radiation efficiency for both arrays is 73.2%. The measured first sidelobe levels are less than –17.5 dB for both polarizations. With competitive performance and low fabrication cost, the proposed dual-polarization ME-dipole antenna array would be valuable for polarization-agile radar and communication systems.
Unmanned Aerial Vehicles for Crowd Monitoring and Analysis
Authors: Husman Muhammad Afif , Albattah Waleed , Abidin Zulkifli Zainal , Mustafah Yasir Mohd. , Kadir Kushsairy , Habib Shabana , Islam Muhammad , Khan Sheroz
Published: November 2021

Crowd monitoring and analysis has become increasingly used for unmanned aerial vehicle applications. From preventing stampede in high concentration crowds to estimating crowd density and to surveilling crowd movements, crowd monitoring and analysis have long been employed in the past by authorities and regulatory bodies to tackle challenges posed by large crowds. Conventional methods of crowd analysis using static cameras are limited due to their low coverage area and non-flexible perspectives and features. Unmanned aerial vehicles have tremendously increased the quality of images obtained for crowd analysis reasons, relieving the relevant authorities of the venues’ inadequacies and of concerns of inaccessible locations and situation. This paper reviews existing literature sources regarding the use of aerial vehicles for crowd monitoring and analysis purposes. Vehicle specifications, onboard sensors, power management, and an analysis algorithm are critically reviewed and discussed. In addition, ethical and privacy issues surrounding the use of this technology are presented.
Functional Connectivity of EEG in Encephalitis during Slow Biphasic Complexes
Authors: Chiarion Giovanni , Mesin Luca
Published: November 2021

The electroencephalogram (EEG) of patients suffering from inflammatory diseases of the brain may show specific waveforms called slow biphasic complexes (SBC). Recent studies indicated a correlation between the severity of encephalitis and some features of SBCs, such as location, amplitude and frequency of appearance. Moreover, EEG rhythms were found to vary before the onset of an SBC, as if the brain was preparing to the discharge (actually with a slowing down of the EEG oscillation). Here, we investigate possible variations of EEG functional connectivity (FC) in EEGs from pediatric patients with different levels of severity of encephalitis. FC was measured by the maximal crosscorrelation of EEG rhythms in different bipolar channels. Then, the indexes of network patterns (namely strength, clustering coefficient, efficiency and characteristic path length) were estimated to characterize the global behavior when they are measured during SBCs or far from them. EEG traces showed statistical differences in the two conditions: clustering coefficient, efficiency and strength are higher close to an SBC, whereas the characteristic path length is lower. Moreover, for more severe conditions, an increase in clustering coefficient, efficiency and strength and a decrease in characteristic path length were observed in the delta–theta band. These outcomes support the hypothesis that SBCs result from the anomalous coordination of neurons in different brain areas affected by the inflammation process and indicate FC as an additional key for interpreting the EEG in encephalitis patients.
Energy for Sustainable Future
Authors: Mahlia T. M. Indra , Fattah I. M. Rizwanul
Published: November 2021

Energy and the environment are interrelated, and they are critical factors that influence the development of societies [...]
Improving Thermal Stability and Hydrophobicity of Rutile-TiO2 Nanoparticles for Oil-Impregnated Paper Application
Authors: Mahmood Katun Mohammed , Kadzutu-Sithole Rudo , Moloto Nosipho , Nyamupangedengu Cuthbert , Gomes Chandima
Published: November 2021

Thermal stress and moisture absorption can cause a synergetic negative impact on kraft paper. Among various approaches for improving the dielectric properties of kraft paper, nanotechnology has had promising results. However, the hydrophilicity of most metal oxide nanoparticles renders nanomodified kraft paper more vulnerable to thermal stress and moisture, thereby inducing degradation. In nanomodified kraft paper research, the use of TiO2 nanoparticles has yielded the most promising results. The major shortfall, however, is the hydrophilicity of TiO2. This work investigated surface modifications of rutile-TiO2 nanoparticles (NPs) for improved hydrophobicity and thermal stability. Rutile-TiO2 NPs is a nontoxic metal oxide that can withstand high temperature and is stable in chemical reactions. Two cases of surfactants were used—alkyl ketene dimer (AKD) and alkenyl succinic anhydride (ASA). The intention was to increase heat resistance and reduce the surface free energy of the rutile-TiO2 NPs. The impacts of the surface modifiers on the rutile-TiO2 NPs were characterised using FT-IR, muffle furnace, analytical weight balance, and TGA. It was discovered that new functional groups were formed on the modified NPs examined through FT-IR spectra. This indicates new chemical bonds, introduced through the surface modification. The unmodified rutile-TiO2 NPs absorbed moisture, increasing their mass by 3.88%, compared with the modified nanoparticles, which released moisture instead. TGA analysis revealed that AKD- and ASA-modified rutile-TiO2 needed higher temperatures than the unmodified rutile-TiO2 to markedly decompose. AKD, however, gave better performance than ASA in that regard. As an example, those modified with 5% AKD sustained a 45% higher temperature than the pure TiO2 nanoparticles. Furthermore, in both cases of the surfactants, the higher the percent of surfactant content was, the more thermally stable the nanoparticles became. This work demonstrates the possibility of fabricating rutile-TiO2 NPs to give improved hydrophobicity and thermal stability for possible dielectric applications such as in kraft paper for power transformer insulation.
Intelligent Reconfigurable Photovoltaic System
Authors: Engel Ekaterina , Kovalev Igor , Testoyedov Nikolay , Engel Nikita E.
Published: November 2021

The global maximum power point tracking of a PV array under partial shading represents a global optimization problem. Conventional maximum power point tracking algorithms fail to track the global maximum power point, and global optimization algorithms do not provide global maximum power point in real-time mode due to a slow convergence process. This paper presents an intelligent reconfigurable photovoltaic system on the basis of a modified fuzzy neural net that includes a convolutional block, recurrent networks, and fuzzy units. We tune the modified fuzzy neural net based on modified multi-dimension particle swarm optimization. Based on the processing of the sensors’ signals and the photovoltaic array’s image, the tuned modified fuzzy neural net generates an electrical interconnection matrix of a photovoltaic total-cross-tied array, which reaches the global maximum power point under non-homogeneous insolation. Thus, the intelligent reconfigurable photovoltaic system represents an effective machine learning application in a photovoltaic system. We demonstrate the advantages of the created intelligent reconfigurable photovoltaic system by simulations. The simulation results reveal robustness against photovoltaic system uncertainties and better performance and control speed of the proposed intelligent reconfigurable photovoltaic system under non-homogeneous insolation as compared to a GA-based reconfiguration total-cross-tied photovoltaic system.
Deep Learning-Based Building Extraction from Remote Sensing Images: A Comprehensive Review
Authors: Luo Lin , Li Pengpeng , Yan Xuesong
Published: November 2021

Building extraction from remote sensing (RS) images is a fundamental task for geospatial applications, aiming to obtain morphology, location, and other information about buildings from RS images, which is significant for geographic monitoring and construction of human activity areas. In recent years, deep learning (DL) technology has made remarkable progress and breakthroughs in the field of RS and also become a central and state-of-the-art method for building extraction. This paper provides an overview over the developed DL-based building extraction methods from RS images. Firstly, we describe the DL technologies of this field as well as the loss function over semantic segmentation. Next, a description of important publicly available datasets and evaluation metrics directly related to the problem follows. Then, the main DL methods are reviewed, highlighting contributions and significance in the field. After that, comparative results on several publicly available datasets are given for the described methods, following up with a discussion. Finally, we point out a set of promising future works and draw our conclusions about building extraction based on DL techniques.
Identification and Characterization of a Novel Recurrent ERCC6 Variant in Patients with a Severe Form of Cockayne Syndrome B
Authors: Zayoud Khouloud , Kraoua Ichraf , Chikhaoui Asma , Calmels Nadège , Bouchoucha Sami , Obringer Cathy , Crochemore Clément , Najjar Dorra , Zarrouk Sinda , Miladi Najoua , Laugel Vincent , Ricchetti Miria , Turki Ilhem , Yacoub-Youssef Houda
Published: November 2021

Cockayne syndrome (CS) is a rare disease caused by mutations in ERCC6/CSB or ERCC8/CSA. We report here the clinical, genetic, and functional analyses of three unrelated patients mutated in ERCC6/CSB with a severe phenotype. After clinical examination, two patients were investigated via next generation sequencing, targeting seventeen Nucleotide Excision Repair (NER) genes. All three patients harbored a novel, c.3156dup, homozygous mutation located in exon 18 of ERCC6/CSB that affects the C-terminal region of the protein. Sanger sequencing confirmed the mutation and the parental segregation in the three families, and Western blots showed a lack of the full-length protein. NER functional impairment was shown by reduced recovery of RNA synthesis with proficient unscheduled DNA synthesis after UV-C radiations in patient-derived fibroblasts. Despite sharing the same mutation, the clinical spectrum was heterogeneous among the three patients, and only two patients displayed clinical photosensitivity. This novel ERCC6 variant in Tunisian patients suggests a founder effect and has implications for setting-up prenatal diagnosis/genetic counselling in North Africa, where this disease is largely undiagnosed. This study reveals one of the rare cases of CS clinical heterogeneity despite the same mutation. Moreover, the occurrence of an identical homozygous mutation, which either results in clinical photosensitivity or does not, strongly suggests that this classic CS symptom relies on multiple factors.
Gonosomal Mosaicism for a Novel COL5A1 Pathogenic Variant in Classic Ehlers-Danlos Syndrome
Authors: Micale Lucia , Foiadelli Thomas , Russo Federica , Cinque Luigia , Bassanese Francesco , Granatiero Matteo , Fusco Carmela , Savasta Salvatore , Castori Marco
Published: November 2021

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the COL5A1 or COL5A2 genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a COL5A1 variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous COL5A1 c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father’s blood specimen suggested the presence of a low-level mosaicism for the COL5A1 variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father’s saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in COL5A1. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.
Children Are Back to School, but Is Play Still in Lockdown? Play Experiences, Social Interactions, and Children’s Quality of Life in Primary Education in the COVID-19 Pandemic in 2020
Authors: Lourenço Ana , Martins Fernando , Pereira Beatriz , Mendes Rui
Published: November 2021

The right to play is crucial for the overall development of children. Several studies highlight the need to have time and space to play, especially at school where children spend much of their time. Unfortunately, in formal education the obsession with academic achievements sidelines and ignores the importance of play. The neglection of play had already reached a critical stage before the pandemic, so data are needed to realize how the right to play in school is presently affected. This paper aims to understand children’s play experience in primary education during the pandemic. It investigates what activities children participated in and what materials were used, and provides insight into the social interactions between peers. Furthermore, children’s quality of life is explored. A group of 370 Portuguese children answered a questionnaire on play and social interactions, alongside with Peds 4.0TM on health-related quality of life (HRQOL). The results showed that recess still emerges as a significant element of children’s daily lives, but COVID-19 has brought limitations on play experiences and peer-interaction. It might also have impacted HRQOL, especially in emotional functioning. Since play, health and well-being are closely connected, play opportunities at school are crucial in helping children to thrive in the pandemic, and should be invested in.
Antecedents of Consumer Food Waste Reduction Behavior: Psychological and Financial Concerns through the Lens of the Theory of Interpersonal Behavior
Authors: Attiq Saman , Chu Amanda , Azam Rauf , Wong Wing-Keung , Mumtaz Sumia
Published: November 2021

This study sought to investigate the role of consumers’ emotional, cognitive, and financial concerns in the development of food waste reduction, reuse, and recycling behavior among restaurant patrons. Food waste in restaurants is a major problem for the food service industry, and it is a growing source of concern in developing countries, where eating out is becoming increasingly popular. A large portion of restaurant food waste in these markets originates from the plates of customers, highlighting the importance of consumer behavior changes in reducing waste. The current study has used a quantitative approach to analyze the impact of anticipated negative emotion of guilt, awareness of consequences, habit, and financial concern on food waste reduction behaviors, i.e., reduce, reuse, and recycle. The study collected 492 responses and data is analyzed for hypotheses testing through Partial Least Square-Structural Equation Modelling. The findings showed that anticipated negative emotions of guilt, awareness of consequences, habit, and financial concern have a significant impact on restaurants’ consumer food waste reduction behaviors. Managers, policymakers, and researchers interested in resolving the food waste problem will find the study useful. Other topics discussed include the implications and limitations as well as possible future research directions.
The Impact of Information Sources on COVID-19-Related Knowledge, Attitudes, and Practices (KAP) among University Students: A Nationwide Cross-Sectional Study
Authors: Baker Israa , Marzouqa Nizar , Yaghi Bashar Nafe’ , Adawi Samer Osama , Yousef Shahd , Sabooh Tayseer Nedal , Salhab Nataly Mazen , Khrishi Hiba Mahmoud , Qabaja Yahya , Riad Abanoub , Kateeb Elham , Attia Sameh
Published: November 2021

COVID-19 is an emerging respiratory disease caused by a novel coronavirus accompanied by a tsunami of misinformation and fake news. This can weaken the public health responses by affecting the COVID-19-related knowledge, attitudes, and practices (KAP) of the public. Therefore, this cross-sectional study was designed during the early stage of the pandemic to evaluate the KAP of Palestinian university students and their commonly used information sources. We found that the most trusted information source among students was the World Health Organization (WHO), followed by the Palestinian Ministry of Health (MoH) briefings and healthcare workers, whereas social media was the most frequently used source of information. The participants exhibited a high level of COVID-19-related knowledge, having an average score of 8.65 (range: 0–10). In total, 76% avoided going to crowded places, and only 33% wore a mask while being outdoors. The vast majority (93%) checked the accuracy of COVID-19-related information before publishing it, 56% used the WHO and MoH briefings for fact-checking, and only 8% relied on healthcare workers. This was particularly the case for those who lived in refugee camps. This study provides an insight into the information sources used by Palestinian university students, the sources they trust, and the information formats they prefer. These results may help public health authorities to locate the information sources through which university students should be targeted. Efforts should be made to recommend healthcare workers as credible information sources. In this way, they will be able to prevent the spread of misleading information and provide high-quality information, especially within unconventional settings such as refugee camps.
Longitudinal Change of Psychological Distress among Healthcare Professionals with and without Psychological First Aid Training Experience during the COVID-19 Pandemic
Authors: Asaoka Hiroki , Koido Yuichi , Kawashima Yuzuru , Ikeda Miki , Miyamoto Yuki , Nishi Daisuke
Published: November 2021

This study aimed to compare longitudinal change of the psychological distress of a group with psychological first aid (PFA) experience and a group without PFA experience among physicians and other healthcare professionals from before the novel coronavirus disease (COVID-19) pandemic to during the pandemic. The baseline survey was conducted in January 2020 (T1). The respondents in T1 were invited to participate in March (T2) and November 2020 (T3). Psychological distress was assessed by the Kessler 6 Scale. Participants were divided into two categories: a group with and a group without PFA experience. Participants were further divided between physicians and healthcare professionals other than physicians, because physicians are more likely to experience morally injurious events. A mixed-model repeated-measures ANOVA was conducted as an indicator of the group differences. In T1, 398 healthcare professionals participated. The longitudinal analysis of healthcare professionals other than physicians showed that psychological distress was significantly greater in the group without PFA experience than in the group with PFA experience (T1 vs. T3). This study showed psychological distress among healthcare professionals other than physicians was significantly greater in the group without PFA experience than in the group with PFA experience during the COVID-19 pandemic, but the results were not consistent among physicians.
Efficiency and Productivity of Public Hospitals in Serbia Using DEA-Malmquist Model and Tobit Regression Model, 2015–2019
Authors: Medarević Aleksandar , Vuković Dejana
Published: November 2021

Improving productivity within health systems using limited resources is a matter of great concern. The objectives of the paper were to evaluate the productivity, efficiency, and impact of environmental factors on efficiency in Serbian hospitals from 2015–2019. Data envelopment analysis, Malmquist index and Tobit regression were applied to hospital data from this period, and public hospitals in Serbia exhibited a great variation regarding their capacity and performance. Between five and eight hospitals ran efficiently from 2015 to 2019, and the productivity of public hospitals increased whereas technical efficiency decreased in the same period. Tobit regression indicated that the proportion of elderly patients and small hospital size (below 200 beds) had a negative correlation with technical efficiency, while large hospital size (between 400 and 600 beds), the ratio of outpatient episodes to inpatient days, bed turnover rate and the bed occupation rate had a positive correlation with technical efficiency. Serbian public hospitals have considerable space for technical efficiency improvement and public action must be taken to improve resource utilization.
Multilevel Determinants of Integrated Service Delivery for Intimate Partner Violence and Mental Health in Humanitarian Settings
Authors: Greene M. Claire , Bencomo Clarisa , Rees Susan , Ventevogel Peter , Likindikoki Samuel , Nemiro Ashley , Bonz Annie , Mbwambo Jessie K. K. , Tol Wietse A. , McGovern Terry M.
Published: November 2021

Inter-agency guidelines recommend that survivors of intimate partner violence in humanitarian settings receive multisectoral services consistent with a survivor-centered approach. Providing integrated services across sectors is challenging, and aspirations often fall short in practice. In this study, we explore factors that influence the implementation of a multisectoral, integrated intervention intended to reduce psychological distress and intimate partner violence in Nyarugusu Refugee Camp, Tanzania. We analyzed data from a desk review of donor, legal, and policy documents; a gender-based violence services mapping conducted through 15 interviews and 6 focus group discussions; and a qualitative process evaluation with 29 stakeholders involved in the implementation of the integrated psychosocial program. We identified the challenges of implementing a multisectoral, integrated intervention for refugee survivors of intimate partner violence at the structural, inter-institutional, intra-institutional, and in social and interpersonal levels. Key determinants of successful implementation included the legal context, financing, inter-agency coordination, engagement and ownership, and the ability to manage competing priorities. Implementing a multisectoral, integrated response for survivors of intimate partner violence is complex and influenced by interrelated factors from policy and financing to institutional and stakeholder engagement. Further investment in identifying strategies to overcome the existing challenges of implementing multisectoral approaches that align with global guidelines is needed to effectively address the burden of intimate partner violence in humanitarian settings.
Healthy Moms and Babies Preventive Psychological Intervention Application: A Study Protocol
Authors: Ruiz-Segovia Natalia , Rodriguez-Muñoz Maria Fe , Olivares Maria Eugenia , Izquierdo Nuria , Coronado Pluvio , Le Huynh-Nhu
Published: November 2021

Depression is the most common psychological disorder during the perinatal period, and its negative effects extend to mothers, babies, their family and society. Scientific evidence points to the urgency of designing preventive interventions and concludes that the gestational period is the most appropriate time to implement these interventions. However, many pregnant women do not seek professional help due to a lack of knowledge about the importance of mental health, its impact, and the available intervention options, as well as a lack of time and financial resources. E-health interventions can be an efficient, cost-effective, and accessible resource for preventing postpartum depression that can circumvent the barriers that pregnant women face. This randomized clinical trial will examine the efficacy of Healthy Moms and Babies, an app aimed at preventing postpartum depressive symptomatology. The second objective of this study is to analyze the effectiveness of the tool in preventing anxious symptomatology. The primary outcome measure is the difference in the mean score between the intervention and control groups on the Patient Health Questionnaire-9 (PHQ-9) at the end of the intervention and at 3 and 6 months postpartum. The secondary outcome will be determined by using the Generalized Anxiety Disorder Screener (GAD-7) at the same time points. The research findings can be used to determine pregnant women’s use of the e-health application for the prevention of postpartum depression, whether the Healthy Moms and Babies intervention app is an effective and useful resource, and what modifications will need to be made to the tool in future updates.
Effects of Mixed of a Ketogenic Diet in Overweight and Obese Women with Polycystic Ovary Syndrome
Authors: Cincione Raffaele Ivan , Losavio Francesca , Ciolli Fabiana , Valenzano Anna , Cibelli Giuseppe , Messina Giovanni , Polito Rita
Published: November 2021

Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome. The relationship between central obesity and the development of insulin resistance is widely verified. Adipose tissue excess and the coexistent dysregulation of adipocyte functions directly contribute to the pathogenesis of the metabolic complications observed in women with PCOS. In the light of these evidence, the most therapeutic option prescribed to obese women with PCOS, regardless of the phenotype e from the severity of clinical expression, is lifestyle correction by diet and physical activity. The aim of this study is to evaluate the beneficial effects of ketogenic diet in 17 obese women with PCOS. Our results showed that the ketogenic diet inducing therapeutic ketosis, improves the anthropometric and many biochemical parameters such as LH, FSH, SHBG, insulin sensitivity and HOMA index. In addition, it induces a reduction in androgenic production, whereas the contextual reduction of fat mass reduced the acyclic production of estrogens deriving from the aromatization in the adipose tissue of the androgenic excess, with an improvement of the LH/FSH ratio. This is the first study on the effects of the ketogenic diet on PCOS, however, further studies are needed to elucidate the mechanism underlying ketogenic diet effects.
Assessment of Dysfunctional Movements and Asymmetries in Children and Adolescents Using the Functional Movement Screen—A Narrative Review
Authors: Vehrs Pat R. , Uvacsek Martina , Johnson Aaron W.
Published: November 2021

The Functional Movement Screen (FMS) is a screening tool that identifies dysfunctional movements in seven test items requiring an interplay of cognitive, perceptual, proprioceptive, and motor functions that involve muscular strength/endurance, flexibility, mobility, coordination, and balance. The results of the FMS include an overall composite score, scores on the individual test items, and identification of compensatory movement patterns and left-right asymmetries on 5 bilateral test items. Although there is a plethora of literature on the use of the FMS in adults, there is a growing body of evidence indicating its use in children. The available research in children involves school children and young athletes in at least 20 different sports in over 20 countries and comparisons between pre- and post-pubescent children, and normal weight, overweight, and obese children. Studies that include measures of adiposity and physical activity levels, or report prevalence of asymmetries and dysfunctional movement patterns are not well represented in the children’s literature. The purpose of this paper is to synthesize the currently available literature in children and suggest potential uses of the FMS by coaches, physical educators, and other health/fitness professionals, appropriate interpretation of results, and future research in children.
Effectiveness of Surgical Approach of Insertion Ventilation Tubes (Tympanostomy) and Adenoidectomy in Comparison with Non-Surgical Approach (Watchful Waiting Approach) in Children at the Age between 1 and 6 and Who Suffer from Otitis Media with Effusion (OME) in 12-Month Period of Observation—The Retrospective Analysis
Authors: Skarzynska Magdalena Beata , Gos Elżbieta , Czajka Natalia , Sanfis Milaine Dominici , Skarzynski Piotr Henryk
Published: November 2021

(1) Background: Otitis media with effusion (OME) is one of the most common diseases in childhood. The objective was to assess clinically the effectiveness of the surgical approach (tube insertion with adenoidectomy) in comparison with the non-surgical approach (watchful waiting) during a 12-month observation period. (2) Methods: This study was retrospective and obtained approval from the bioethics committee. The criteria of inclusion in the first group (surgical approach) were: (1) a diagnosis of chronic otitis media with effusion in children aged between 1 and 6 years; (2) their medical history showed that they had undergone adenoidectomy and tympanostomy with the insertion of ventilation tubes (VTs). The criteria for inclusion in the second group (non-surgery) were similar to the first group except that their medical history showed they had not undergone adenoidectomy or tympanostomy with the insertion of VTs. There were 422 children included in the surgical group and 50 children in the non-surgical group, and the period of observation was 12 months. (3) Results: For the entire surgical group, the number of healthy days ranged from 20 to 365, with a mean of 328.0 days (SD = 91.4).In the non-surgical group, the number of healthy days ranged from 13 to 365, with a mean of 169.2 days (SD = 127.3). The difference in the number of healthy days was statistically significant (p < 0.001). The certainty of treatment in the first group was higher than in the second group, and the number of days without recurrence was significantly higher than in the second group. In the first group, there were 71 recurrences from 422 children (16.8%), and, in the second subgroup, there were 40 recurrences of acute otitis media (AOM) from 50 children (80%). The RR was 0.21. (4) Conclusions: The surgical approach in children aged 1–6 years who have been diagnosed with otitis media with effusion is reasonable and beneficial for the child.