bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact on the Clinical Evolution of Patients with COVID-19 Pneumonia and the Participation of the NFE2L2/KEAP1 Polymorphisms in Regulating SARS-CoV-2 Infection
Authors: Soto María Elena , Fuentevilla-Álvarez Giovanny , Palacios-Chavarría Adrián , Vázquez Rafael Ricardo Valdez , Herrera-Bello Héctor , Moreno-Castañeda Lidia , Torres-Paz Yazmín Estela , González-Moyotl Nadia Janet , Pérez-Torres Idalia , Aisa-Alvarez Alfredo , Manzano-Pech Linaloe , Pérez-Torres Israel , Huesca-Gómez Claudia , Gamboa Ricardo
Published: December 2022

In patients with severe pneumonia due to COVID-19, the deregulation of oxidative stress is present. Nuclear erythroid factor 2 (NRF2) is regulated by KEAP1, and NRF2 regulates the expression of genes such as NFE2L2-KEAP1, which are involved in cellular defense against oxidative stress. In this study, we analyzed the participation of the polymorphisms of NFE2L2 and KEAP1 genes in the mechanisms of damage in lung disease patients with SARS-CoV-2 infection. Patients with COVID-19 and a control group were included. Organ dysfunction was evaluated using SOFA. SARS-CoV-2 infection was confirmed and classified as moderate or severe by ventilatory status and by the Berlin criteria for acute respiratory distress syndrome. SNPs in the gene locus for NFE2L2, rs2364723C>G, and KEAP1, rs9676881A>G, and rs34197572C>T were determined by qPCR. We analyzed 110 individuals with SARS-CoV-2 infection: 51 with severe evolution and 59 with moderate evolution. We also analyzed 111 controls. Significant differences were found for rs2364723 allele G in severe cases vs. controls (p = 0.02); for the rs9676881 allele G in moderate cases vs. controls (p = 0.04); for the rs34197572 allele T in severe cases vs. controls (p = 0.001); and in severe vs. moderate cases (p = 0.004). Our results showed that NFE2L2 rs2364723C>G allele G had a protective effect against severe COVID-19, while KEAP1 rs9676881A>G allele G and rs34197572C>T minor allele T were associated with more aggressive stages of COVID-19.
Transient Receptor Potential Channels and Itch
Authors: Mahmoud Omar , Soares Georgia Biazus , Yosipovitch Gil
Published: December 2022

Transient Receptor Potential (TRP) channels are multifunctional sensory molecules that are abundant in the skin and are involved in the sensory pathways of itch, pain, and inflammation. In this review article, we explore the complex physiology of different TRP channels, their role in modulating itch sensation, and their contributions to the pathophysiology of acute and chronic itch conditions. We also cover small molecule and topical TRP channel agents that are emerging as potential anti-pruritic treatments; some of which have shown great promise, with a few treatments advancing into clinical trials—namely, TRPV1, TRPV3, TRPA1, and TRPM8 targets. Lastly, we touch on possible ethnic differences in TRP channel genetic polymorphisms and how this may affect treatment response to TRP channel targets. Further controlled studies on the safety and efficacy of these emerging treatments is needed before clinical use.
Multifaceted Benefits of GDF11 Treatment in Spinal Cord Injury: In Vitro and In Vivo Studies
Authors: Tsai May-Jywan , Fay Li-Yu , Liou Dann-Ying , Chen Yi , Chen Ya-Tzu , Lee Meng-Jen , Tu Tsung-Hsi , Huang Wen-Cheng , Cheng Henrich
Published: December 2022

Traumatic spinal cord injury (SCI) initiates a series of cellular and molecular events that include both primary and secondary injury cascades. This secondary cascade provides opportunities for the delivery of therapeutic intervention. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, regulates various biological processes in mammals. The effects of GDF11 in the nervous system were not fully elucidated. Here, we perform extensive in vitro and in vivo studies to unravel the effects of GDF11 on spinal cord after injury. In vitro culture studies showed that GDF11 increased the survival of both neuronal and oligodendroglial cells but decreased microglial cells. In stressed cultures, GDF11 effectively inhibited LPS stimulation and also protected neurons from ischemic damage. Intravenous GDF11 administration to rat after eliciting SCI significantly improved hindlimb functional restoration of SCI rats. Reduced neuronal connectivity was evident at 6 weeks post-injury and these deficits were markedly attenuated by GDF11 treatment. Furthermore, SCI-associated oligodendroglial alteration were more preserved by GDF11 treatment. Taken together, GDF11 infusion via intravenous route to SCI rats is beneficial, facilitating its therapeutic application in the future.
A Skeletal Muscle-Centric View on Time-Restricted Feeding and Obesity under Various Metabolic Challenges in Humans and Animals
Authors: Livelo Christopher , Guo Yiming , Melkani Girish C.
Published: December 2022

Nearly 50% of adults will suffer from obesity in the U.S. by 2030. High obesity rates can lead to high economic and healthcare burdens in addition to elevated mortality rates and reduced health span in patients. Emerging data demonstrate that obesity is a multifactorial complex disease with various etiologies including aging, a lifestyle of chronic high-fat diets (HFD), genetic predispositions, and circadian disruption. Time-restricted feeding/eating (TRF; TRE in humans) is an intervention demonstrated by studies to show promise as an effective alternative therapy for ameliorating the effects of obesity and metabolic disease. New studies have recently suggested that TRF/TRE modulates the skeletal muscle which plays a crucial role in metabolism historically observed to be impaired under obesity. Here we discuss recent findings regarding potential mechanisms underlying TRF’s modulation of skeletal muscle function, metabolism, and structure which may shed light on future research related to TRF as a solution to obesity.
Relevance of the Exocyst in Arabidopsis exo70e2 Mutant for Cellular Homeostasis under Stress
Authors: Neves João , Monteiro João , Sousa Bruno , Soares Cristiano , Pereira Susana , Fidalgo Fernanda , Pissarra José , Pereira Cláudia
Published: December 2022

Plants must adapt to cope with adverse environmental conditions that affect their growth and development. To overcome these constraints, they can alter their developmental patterns by modulating cellular processes and activating stress-responsive signals. Alongside the activation of the antioxidant (AOX) system, a high number of genes are expressed, and proteins must be distributed to the correct locations within the cell. The endomembrane system and associated vesicles thus play an important role. Several pathways have been associated with adverse environmental conditions, which is the case for the exocyst-positive organelle—EXPO. The present work, using Arabidopsis mutants with T-DNA insertions in the gene EXO70, essential for EXPO vesicles formation, was designed to characterise the anatomical (morphology and root length), biochemical (quantification of stress markers and antioxidant system components), and molecular responses (gene expression) to abiotic stresses (saline, drought, oxidative, and metal-induced toxicity). The results obtained showed that mutant plants behave differently from the wild type (WT) plants. Therefore, in the exo70 mutant, morphological changes were more noticeable in plants under stress, and the non-enzymatic component of the antioxidant system was activated, with no alterations to the enzymatic component. Furthermore, other defence strategies, such as autophagy, did not show important changes. These results confirmed the EXPO as an important structure for tolerance/adaptation to stress.
Cas9/gRNA-Mediated Mutations in PtrFLA40 and PtrFLA45 Reveal Redundant Roles in Modulating Wood Cell Size and SCW Synthesis in Poplar
Authors: Zhen Cheng , Hua Xinguo , Jiang Xue , Tong Guimin , Li Chunming , Yang Chuanping , Cheng Yuxiang
Published: December 2022

Fasciclin-like arabinogalactan proteins (FLAs) play an important role in plant development and adaptation to the environment. However, the roles of FLAs in wood formation remain poorly understood. Here, we identified a total of 50 PtrFLA genes in poplar. They were classified into four groups: A to D, among which group A was the largest group with 28 members clustered into four branches. Most PtrFLAs of group A were dominantly expressed in developing xylem based on microarray and RT-qPCR data. The roles of PtrFLA40 and PtrFLA45 in group A were investigated via the Cas9/gRNA-induced mutation lines. Loss of PtrFLA40 and PtrFLA45 increased stem length and diameter in ptrfla40ptrfla45 double mutants, but not in ptrfla40 or ptrfla45 single mutants. Further, our findings indicated that the ptrfla40ptrfla45 mutants enlarged the cell size of xylem fibers and vessels, suggesting a negative modulation in stem xylem cell size. In addition, wood lignin content in the ptrfla40fla45 mutants was increased by nearly 9%, and the lignin biosynthesis-related genes were significantly up-regulated in the ptrfla40fla45 mutants, in agreement with the increase in wood lignin content. Overall, Cas9/gRNA-mediated mutations in PtrFLA40 and PtrFLA45 reveal redundant roles in modulating wood cell size and secondary cell wall (SCW) synthesis in poplar.
Protein Kinase CK2 Contributes to Glucose Homeostasis by Targeting Fructose-1,6-Bisphosphatase 1
Authors: Pack Mandy , Gulde Tim Nikolai , Völcker Michelle Victoria , Boewe Anne S. , Wrublewsky Selina , Ampofo Emmanuel , Montenarh Mathias , Götz Claudia
Published: December 2022

Glucose homeostasis is of critical importance for the survival of organisms. It is under hormonal control and often coordinated by the action of kinases and phosphatases. We have previously shown that CK2 regulates insulin production and secretion in pancreatic β-cells. In order to shed more light on the CK2-regulated network of glucose homeostasis, in the present study, a qRT-PCR array was carried out with 84 diabetes-associated genes. After inhibition of CK2, fructose-1,6-bisphosphatase 1 (FBP1) showed a significant lower gene expression. Moreover, FBP1 activity was down-regulated. Being a central enzyme of gluconeogenesis, the secretion of glucose was decreased as well. Thus, FBP1 is a new factor in the CK2-regulated network implicated in carbohydrate metabolism control.
Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM/MM Approach
Authors: Wang Zijian , Zhang Qingzhu , Wang Guoqiang , Wang Wenxing , Wang Qiao
Published: December 2022

Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: (Ⅰ) serine-initiated nucleophilic attack and (Ⅱ) C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps Ⅰ and Ⅱ, respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based kcat prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein–substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
In Vivo Efficacy of Wound Healing under External (Bio)AgNCs Treatment: Localization Case Study in Liver and Blood Tissue
Authors: Railean Viorica , Buszewska-Forajta Magdalena , Rodzik Agnieszka , Gołębiowski Adrian , Pomastowski Paweł , Buszewski Bogusław
Published: December 2022

The present study reports on the in vivo application of (Bio)silver nanocomposite formulations (LBPC-AgNCs) on wound healing. Additionally, the present study emphasizes the limited uptake of silver by liver and blood tissues as well as the high viability of PBMCs following external LBPC-AgNCs treatment. The wound closure was monitored via stereoscopic microscope, a localization case study in liver and blood tissue was carried out by (Inductively Coupled Plasma–Mass Spectrometers (ICP/MS), and peripheral blood mononuclear cells (PMBC) viability was determined via flow cytometry technique. The silver formulation was applied externally on the site of the wound infection for a period of ten days. At the beginning of the experiment, a moderate decrease in body weight and atypical behavior was observed. However, during the last period of the experiment, no abnormal mouse behaviors were noticed. The wound-healing process took place in a gradual manner, presenting the regeneration effect at around 30% from the fourth day. From the seventh day, the wounds treated with the silver formulation showed 80% of the wound healing potential. The viability of PBMCs was found to be 97%, whereas the concentrations of silver in the liver and blood samples were determined to be 0.022 µg/g and 9.3 µg/g, respectively. Furthermore, the present report becomes a pilot study in transferring from in vitro to in vivo scale (e.g., medical field application) once LBPC-AgNCs have demonstrated a unique wound healing potential as well as a non-toxic effect on the liver and blood.
Investigation of Photoelectrochemical Performance under the Piezoelectric Effect Based on Different Zinc Oxide Morphologies
Authors: Wang Dong , Liu Rui , Han Changcun , Tan Baohua , Fu Qian , Liu Zhifeng
Published: December 2022

Recently, the piezoelectric effect has been widely used in photoelectrochemical (PEC) water splitting, and the morphology of the piezoelectric material is a critical factor affecting the piezo-photoelectrochemical water splitting performance. Herein, we explored the mechanism of the piezo-photoelectrochemical performance of zinc oxide (ZnO) that is affected by the morphology. Firstly, three different ZnO nanostructures (nanosheets, nanorods, and nanospheres) were synthesized by the electrodeposition, hydrothermal, and sol-gel methods, respectively. Then, the measurements of PEC water splitting performance under the piezoelectric effect revealed a 3-fold increase for the ZnO nanosheets, a 1.4-fold increase for the nanorods, and a 1.2-fold increase for the nanospheres compared to no piezoelectric effect. Finally, finite element simulation showed that nanosheets generated the highest piezoelectric potential (0.6 V), followed by nanorods (0.2 V), and nanospheres the lowest (0.04 V). Thus, among the three morphologies, the ZnO nanosheets exhibited a great improvement in PEC performance under the piezoelectric effect. The great improvement is due to the non-axial vertical homogeneous growth of the ZnO nanosheets, subjecting them to the highest effective deformation stress, which enables the ZnO nanosheets to produce the highest piezoelectric potential to accelerate the carrier separation and limit the recombination of photoelectrons and holes. This work serves as a guide for developing various photoelectrodes that are used in piezo-photoelectrochemical water splitting.
Mating Competitiveness of Irradiated Lobesia botrana (Lepidoptera: Tortricidae) in Male-Only and Both Sex Release Strategies under Laboratory Cage Conditions
Authors: Saour George , Hashem Ali , Jassem Iyad
Published: December 2022

This laboratory study explored the concept of whether irradiated male-only releases are more or equally efficient as releases of both irradiated males and females in the context of using the sterile insect technique/inherited sterility (SIT/IS) for the management of the European grapevine moth Lobesia botrana. The current study examined the mating competitiveness of 150-Gy-treated L. botrana male and female moths or 150-Gy-treated male moths only, with untreated moths in laboratory cages. Our results showed that the release of both sexes significantly increased the competitiveness value (C) and the biological efficiency index (BE) as compared with male-only release, and this was independent of the male to untreated male ratio. Moreover, a single release of 150-Gy-treated and untreated males and females at a 1:1:10:10 ratio (untreated male:untreated female: treated male:treated female) significantly reduced egg hatch, and the number of first-generation offspring (F1) was small. The emergence of F2-moths per untreated F1 male and female moth was low, but these undesired fertile moths should be eliminated in order to achieve effective control. The results presented herein provide useful information on the impact of 150-Gy-treated male-only, versus releases of both treated males and females on untreated moths, which is essential to managing L. botrana populations with SIT/IS.
Climatic Niche, Altitudinal Distribution, and Vegetation Type Preference of the Flea Beetle Genus Arsipoda in New Caledonia (Coleoptera Chrysomelidae)
Authors: Biondi Maurizio , D’Alessandro Paola , Iannella Mattia
Published: December 2022

New Caledonia is one of the major biodiversity hotspots. The flea beetle genus Arsipoda (Coleoptera Chrysomelidae) is present with 21 species, all endemic. We investigated, using GIS analyses and ecological niche models, the habitat preferences of these species in terms of vegetation types, altitude, and climate, and assessed the adequacy of knowledge on the spatial parameters affecting the distribution of the genus in New Caledonia. Altitude and geology seem to play an important role in shaping species distribution. Volcanic substrate allows the growth of ultramafic vegetation, which includes most of their host plants. From a biogeographic and conservation perspective, our results report a deep link between Arsipoda species and their habitats, making them particularly sensitive to environmental modifications.
Systematic Position of the Fossil Burrower Bug Eocenocydnus lisi Popov, 2019 (Hemiptera, Heteroptera, Cydnidae) Revealed by a Parallel/Cross-Eyed Viewing Method Used for Obtaining Three-Dimensional Images
Authors: Lis Jerzy A.
Published: December 2022

The fossil burrower bug Eocenocydnus lisi described from the Late Eocene of the Isle of Wight, UK, is analysed using a parallel, cross-eyed viewing method. The species, tentatively placed in the subfamily Sehirinae, is redescribed and its systematic position is discussed. Newly recovered morphological characteristics allow it to be placed in the tribe Cydnini of the subfamily Cydninae.
Dermestes (s.str.) haemorrhoidalis (Coleoptera: Dermestidae)—The Most Frequent Species on Mummified Human Corpses in Indoor Conditions? Three Cases from Southwestern Poland
Authors: Kadej Marcin , Szleszkowski Łukasz , Thannhäuser Agata , Jurek Tomasz
Published: December 2022

Beetles of the family Dermestidae, especially of the genus Dermestes Linnaeus, 1758, are often identified on corpses in late stages of decomposition. They usually feed on remains devoid of organs and soft tissues or when the corpses undergo mummification. In Europe, eight species from two subgenera Dermestes and Dermestinus Zhantiev, 1967, have so far been identified on human corpses. Despite the relatively frequent presence of Dermestes sp. in experimental studies conducted in Poland, no reports concerning Dermestes directly collected from human corpses have been published to date. This article again describes observations of Dermestidae collected from human corpses found in indoor conditions in Wrocław, the capital of the Dolnośląskie Voivodeship. For the second time, there is evidence of the presence of Dermestes (s.str.) haemorrhoidalis on human corpses—a species considered to be relatively rare, as evidenced by faunistic data published from Poland, as well as the results of ongoing experiments of forensic interest.
Microencapsulation of Capsaicin in Chitosan Microcapsules: Characterization, Release Behavior, and Pesticidal Properties against Tribolium castaneum (Herbst)
Authors: Cui Su-Fen , Wang Jin-Wei , Li Hai-Feng , Fang Ran , Yu Xin , Lu Yu-Jie
Published: December 2022

Capsaicin is a capsaicinoid in hot chili peppers, with excellent antibacterial and antimicrobial activities and a good safety profile, but its poor solubility and instability restrict its effectiveness. This limitation may be mitigated by encapsulation. Herein, capsaicin microcapsules (CCMs) were prepared through layer-by-layer self-assembly, using chitosan and carboxymethyl chitosan as shell materials. The chemical and microstructure structural characterization was evaluated by the methods of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The SEM indicated the microcapsules were irregular in shape with an average size of about 100 μm. The encapsulation had a high loading efficiency of 64.31%. FTIR and XRD revealed the absence of the interaction between the core and shell materials and the amorphous nature of the CCMs. The analysis results of the microcapsules’ release behavior showed the burst release of capsaicin in 7 days and a slow progression afterward in three solutions, with the highest release properties in a basic solution, followed by acidic and neutral salt solutions. The entomotoxicity of CCMs was conducted against Tribolium castaneum (Herbst), and its efficacy was compared with pure capsaicin. The CCMs were found to be highly effective against this pest. The LC50 value for capsaicin and its microcapsules was 31.37 and 29.75 mg/kg on adults, respectively. According to these values, T. castaneum’s development and reproduction were significantly inhibited compared with the control group. The excellent physicochemical characteristics and insecticidal performance show a high application value for integrated pest control.
Research and Development of Criterial Correlations for the Optimal Grid Element Size Used for RANS Flow Simulation in Single and Compound Channels
Authors: Bryzgunov Pavel , Osipov Sergey , Komarov Ivan , Rogalev Andrey , Rogalev Nikolay
Published: December 2022

At present, software products for numerical simulation of fluid dynamics problems (ANSYS Fluent, Ansys CFX, Star CCM, Comsol, etc.) problems are widely used. These software products are mainly based on the numerical solution of the Navier–Stokes equations, the most common and computationally easy method of solving, which is Reynolds averaging (RANS), and further closing the system using semi-empirical turbulence models. Currently, there are many modeling methods and turbulence models; however, there are no generalized recommendations for setting up grid models for modeling flows, while for practical use both the correct mathematical models and the setting of the computational grid are important. In particular, there are no generalized recommendations on the choice of scale of global elements of grid models for typical single channels. This work is devoted to the development and study of relations for a priori estimation of the parameters of a grid model in relation to solving hydrodynamic problems with fluid flow in channels. The paper proposes the introduction of a generalized grid convergence criterion for single channels at high Reynolds numbers. As single channels, a channel with a sudden expansion, a channel with a sudden contraction, and diffuser channels with different opening angles are considered. Based on the results of variant calculations of typical single channels at various Reynolds numbers and various geometric parameters, generalized criterion correlations were obtained to find dimensionless linear scales of grid elements relative to the hydrodynamic characteristics of the flow in the channel. Variant calculations of the compound channel were investigated, which showed the adequacy of correlations proposed.
METTL3-Mediated lncSNHG7 m6A Modification in the Osteogenic/Odontogenic Differentiation of Human Dental Stem Cells
Authors: Yang Yeqing , Zeng Junkai , Jiang Chong , Chen Jiawen , Song Ci , Chen Ming , Wu Buling
Published: December 2022

Background: Human dental pulp stem cells (hDPSCs) play an important role in endodontic regeneration. N6-methyladenosine (m6A) is the most common RNA modification, and noncoding RNAs have also been demonstrated to have regulatory roles in the expression of m6A regulatory proteins. However, the study on m6A modification in hDPSCs has not yet been conducted. Methods: Single base site PCR (MazF) was used to detect the m6A modification site of lncSNHG7 before and after mineralization of hDPSCs to screen the target m6A modification protein, and bioinformatics analysis was used to analyze the related pathways rich in lncSNHG7. After knockdown and overexpression of lncSNHG7 and METTL3, the osteogenic/odontogenic ability was detected. After METTL3 knockdown, the m6A modification level and its expression of lncSNHG7 were detected by MazF, and their binding was confirmed. Finally, the effects of lncSNHG7 and METTL3 on the Wnt/β-catenin pathway were detected. Results: MazF experiments revealed that lncSNHG7 had a m6A modification before and after mineralization of hDPSCs, and the occurrence site was 2081. METTL3 was most significantly upregulated after mineralization of hDPSCs. Knockdown/ overexpression of lncSNHG7 and METTL3 inhibited/promoted the osteogenic/odontogenic differentiation of hDPSCs. The m6A modification and expression of lncSNHG7 were both regulated by METTL3. Subsequently, lncSNHG7 and METTL3 were found to regulate the Wnt/β-catenin signaling pathway. Conclusion: These results revealed that METTL3 can activate the Wnt/β-catenin signaling pathway by regulating the m6A modification and expression of lncSNHG7 in hDPSCs to enhance the osteogenic/odontogenic differentiation of hDPSCs. Our study provides new insight into stem cell-based tissue engineering.
Differential Effects of Patient Navigation across Latent Profiles of Barriers to Care among People Living with HIV and Comorbid Conditions
Authors: Traynor Sharleen M. , Schmidt Renae D. , Gooden Lauren K. , Matheson Tim , Haynes Louise , Rodriguez Allan , Mugavero Michael , Jacobs Petra , Mandler Raul , Del Rio Carlos , Carrico Adam W. , Horigian Viviana E. , Metsch Lisa R. , Feaster Daniel J.
Published: December 2022

Engaging people living with HIV who report substance use (PLWH-SU) in care is essential to HIV medical management and prevention of new HIV infections. Factors associated with poor engagement in HIV care include a combination of syndemic psychosocial factors, mental and physical comorbidities, and structural barriers to healthcare utilization. Patient navigation (PN) is designed to reduce barriers to care, but its effectiveness among PLWH-SU remains unclear. We analyzed data from NIDA Clinical Trials Network’s CTN-0049, a three-arm randomized controlled trial testing the effect of a 6-month PN with and without contingency management (CM), on engagement in HIV care and viral suppression among PLWH-SU (n = 801). Latent profile analysis was used to identify subgroups of individuals’ experiences to 23 barriers to care. The effects of PN on engagement in care and viral suppression were compared across latent profiles. Three latent profiles of barriers to care were identified. The results revealed that PN interventions are likely to be most effective for PLWH-SU with fewer, less severe healthcare barriers. Special attention should be given to individuals with a history of abuse, intimate partner violence, and discrimination, as they may be less likely to benefit from PN alone and require additional interventions.
Procedural Tools and Technics for Transcatheter Paravalvular Leak Closure: Lessons from a Decade of Experience
Authors: Hascoët Sébastien , Smolka Grzegorz , Kilic Teoman , Ibrahim Reda , Onorato Eustaquio-Maria , Calvert Patrick , Champagnac Didier , Freixa-Rofastes Xavier , Zorinas Aleksejus , Sandoval Juan , Ducrocq Gregory , Bouisset Frederic , Fraisse Alain , Gerardin Benoit
Published: December 2022

Prosthetic paravalvular leaks (PVLs) are associated with congestive heart failure and hemolysis. Surgical PVL closure carries high risks. Transcatheter implantation of occluding devices in PVL is a lower risk but challenging procedure. Of the available devices, only two have been specifically approved in Europe for transcatheter PVL closure (tPVLc): the Occlutech® Paravalvular Leak Device (PLD) and Amplatzer™ ParaValvular Plug 3 (AVP 3). Here, we review the various tools and devices used for tPVLc, based on three observational registries including 748 tPVLc procedures performed in 2005–2021 at 33 centres in 11 countries. In this case, 12 registry investigators with over 20 tPVLc procedures each described their practical tips and tricks regarding imaging, approaches, delivery systems, and devices. They considered three-dimensional echocardiography to be the cornerstone of PVL assessment and procedure guidance. Anterograde trans-septal mitral valve and retrograde aortic approaches were used in most centres, although some investigators preferred the transapical approach. Hydrophilic-coated low-profile sheaths were used most often for device deployment. The AVP 3 and PLD devices were chosen for 89.0% of procedures. Further advances in design and materials are awaited. These complex procedures require considerable expertise, and experience accumulated over a decade has no doubt contributed to improve practices.
Psychological Characteristics and Quality of Life of Patients with Upper and Lower Functional Gastrointestinal Disorders
Authors: Jang Seung-Ho , Choi Suck-Chei , Kim Yong-Sung , Ryu Han-Seung , Lee Sang-Yeol , Bahk Won-Myong
Published: December 2022

Background: This study aimed to identify the differences in the psychological characteristics of the anatomical location of functional gastrointestinal disorders (FGIDs) and the factors that influence the quality of life (QOL). Methods: Altogether, 233 patients with FGIDs were classified into the upper gastrointestinal disorder (UGID; n = 175) group and the lower gastrointestinal disorder group (LGID; n = 58). Psychological characteristics and QOL were evaluated using the validated questionnaires. Results: The LGID group demonstrated higher scores in ‘emotional depression’ than the UGID group in depressive symptoms (t = −3.031, p < 0.01). A significant difference was observed between groups in ‘significant others’ in social supports (t = 2.254, p < 0.05). Significant differences were observed between the groups in hardiness (t = 2.259, p < 0.05) and persistence (t = 2.526, p < 0.05) in resilience, while the LGID group demonstrated significantly lower scores than the UGID group in ‘negative affectivity’ in type-D personality (t = −1.997, p < 0.05). Additionally, the LGID group demonstrated lower QOL than the UGID group (t = 2.615, p < 0.05). The stepwise regression analysis on QOL involved depression, resilience, social support, and childhood trauma, which accounted for 48.4% of the total QOL explanatory variance. Conclusions: Psychological characteristics and QOL significantly differed when FGIDs were classified according to anatomical location. Thus, psychological interventions customized for each type of FGIDs may be necessary for effective treatment.
Adiponectin and Interleukin-33: Possible Early Markers of Metabolic Syndrome
Authors: Nesic Jelena , Ljujic Biljana , Rosic Vesna , Djukic Aleksandar , Rosic Milenko , Petrovic Ivica , Zornic Nenad , Jovanovic Ivan P , Petrovic Sara , Djukic Svetlana
Published: December 2022

Adiponectin is one of the most important molecules in the body’s compensatory response to the development of insulin resistance. By trying to maintain insulin sensitivity, increase insulin secretion and prevent inflammation, adiponectin tries to maintain glucose homeostasis. Interleukin-33, which belongs to the group of alarmins, also promotes insulin secretion. Interleukin-33 might be either pro-inflammatory or anti-inflammatory depending on the disease and the model. However, interleukin-33 has shown various protective effects in CVD, obesity and diabetes. The aim of our study was to investigate the association between adiponectin and interleukin-33 in patients with metabolic syndrome. As expected, all patients with metabolic syndrome had worse parameters that represent the hallmark of metabolic syndrome compared to the control group. In the subgroup of patients with low adiponectin, we observed less pronounced characteristics of metabolic syndrome simultaneously with significantly higher values of interleukin-33 compared to the subgroup of patients with high adiponectin. Our findings suggested that adiponectin might be an early marker of metabolic syndrome that emerges before anthropomorphic, biochemical and clinical parameters. We also suggest that both interleukin-33 and adiponectin may be used to predict the inflammatory status in the early stage of metabolic syndrome.
Aero-Medical Evacuation during SARS-CoV-2 Pandemic: Extraordinary Measure or Emerging Treatment Option?
Authors: Benvenuto Domenico , Ascoli Bartoli Tommaso , Curtolo Ambrogio , Palazzolo Claudia , Vita Serena , Mariano Andrea , Scorzolini Laura , Ippolito Giuseppe , Marchioni Luisa , Cerini Federico , D’Offizi Gianpiero , Vaia Francesco , Nicastri Emanuele
Published: December 2022

Aero-medical evacuation has been considered as a feasible and safe treatment option during COVID pandemic, particularly when the needs of affected patients exceed what local clinics and hospitals are supposed to provide. In this article, we analyzed the clinical course of 17 patients medically evacuated to the “L. Spallanzani” Institute in Rome, Italy from foreign countries, mainly Africa and Eastern Europe, who had COVID-19 pneumonia with, or without, coinfections such as malaria, HIV, tuberculosis and microbiologically confirmed sepsis syndrome. The aero-medical evacuation of patients with infectious diseases has become one of the greatest medical achievements we have reached during this pandemic; in fact, only two patients with life threatening coinfections have died. Although logistically difficult and cost consuming, medical evacuation should be considered as a treatment option more than a single extraordinary measure, especially among complex cases that require specific technical and human resources.
Decreased Physical and Daily Living Activities in Patients with Peripheral Arterial Disease on Hemodialysis
Authors: Tamura Yuma , Takahashi Harunori , Sakai Daiki , Tsurumi Tomoki , Tamiya Hajime , Ueno Asuka , Kawamoto Shinya , Shimoyama Masahiro , Yasu Takanori
Published: December 2022

Decreased physical activity and activities of daily living (ADL) in patients on hemodialysis (HD) are associated with a poor prognosis. Additionally, comorbid peripheral arterial disease is associated with further deterioration. We conducted a cross-sectional study of ADL difficulty and life-space assessment (LSA) in three groups of patients on hemodialysis according to their ankle-brachial index (ABI) values. The 164 patients were divided into ABI Low (ABI < 0.9), Normal (0.9 ≤ ABI < 1.3), and High (1.3 ≤ ABI) groups, and compared using analysis of covariance with LSA and ADL difficulty adjusted for age. The Kihon checklist (KCL) was used to assess the presence of frailty. The LSA was lower in the Low group than in the High group (F = 3.192, p = 0.044). Similarly, the ADL difficulty was significantly lower in the Low group than in the Normal group (F = 3.659, p = 0.028). In the Low group, the proportion of patients with frailty was 47.1% and KCL physical was significantly lower, indicating that patients on HD with a lower ABI had a higher prevalence of frailty and lower LSA and ADL difficulty. In conclusion, patients on HD with decreased ABI values most likely exhibit decline in physical activity and ADL due to frailty and claudication.
Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer
Authors: Nakao Akira , Inoue Hiroyuki , Ikeuchi Nobumitsu , Igata Fumiyasu , Aoyama Takashi , Hamasaki Makoto , Arima Hisatomi , Fujita Masaki
Published: December 2022

Background: Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people. Objective: We aimed to examine the impact of the results of the TTF-1 immunostaining of tumor cells on the therapeutic effect of chemotherapy in Japanese patients with nonsq NSCLC. Methods: We examined the results of TTF-1 immunostaining and the clinical background of Japanese patients with nonsq NSCLC who received platinum-doublet chemotherapy at our hospital, from April 2009 to April 2021, and the correlation between regimens with or without pemetrexed in progression-free survival (PFS) and overall survival (OS). The efficacy of each regimen was then compared between TTF-1-positive and TTF-1-negative tumors. Results: TTF-1 immunostaining was performed in 145 patients during the study period: 92 were positive, and 53 were negative. A total of 24 patients presented with EGFR/ALK gene abnormality (16.6%). The PFS and OS of patients who were TTF-1-positive tended to be longer than those of the patients who were TTF-1-negative under either regimen. In other words, patients who were TTF-1-negative were frequently resistant to numerous chemotherapy drugs and experienced a poor prognosis under both regimens. The OS of patients who were TTF-1-positive and treated with the pemetrexed regimen was significantly longer than those on regimens without pemetrexed (963 vs. 412 days, HR = 0.73; 95% CI 0.55–0.96, p = 0.022), whereas there was no difference in PFS. Conclusions: The positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who have advanced nonsq NSCLC. Our analysis examined the possibility of a pemetrexed regimen leading to a longer prognosis in Asian patients who were TTF-1-positive for nonsq NSCLC, as shown in previous studies.
Oxygen Extraction and Mortality in Patients Undergoing Chronic Haemodialysis Treatment: A Multicentre Study
Authors: Rotondi Silverio , Tartaglione Lida , Muci Maria Luisa , Pasquali Marzia , Panocchia Nicola , Aucella Filippo , Gesuete Antonio , Papalia Teresa , Solmi Luigi , Farcomeni Alessio , Mazzaferro Sandro
Published: December 2022

Patients on haemodialysis (HD) suffer a high mortality rate linked to developing subclinical hypoxic parenchymal stress during HD sessions. The oxygen extraction ratio (OER), an estimate of the oxygen claimed by peripheral tissues, might represent a new prognostic factor in HD patients. This study evaluated whether the intradialytic change in OER (ΔOER) identified patients with higher mortality risks. We enrolled chronic HD patients with permanent central venous catheters with available central venous oxygen saturation (ScvO2) measurements; the arterial oxygen saturation was measured with peripheral oximeters (SpO2). We measured OER before and after HD at enrolment; deaths were recorded during two-years of follow-up. In 101 patients (age: 72.9 ± 13.6 years, HD vintage: 9.6 ± 16.6 years), 44 deaths were recorded during 11.6 ± 7.5 months of follow-up. Patients were divided into two groups according to a 40% ΔOER threshold (ΔOER < 40%, n = 56; ΔOER ≥ 40%, n = 45). The ΔOER ≥ 40% group showed a higher incidence of death (60% vs. 30%; p = 0.005). The survival curve (log-rank-test: p = 0.0001) and multivariate analysis (p = 0.0002) confirmed a ΔOER ≥ 40% as a mortality risk factor. This study showed the intradialytic ΔOER ≥ 40% was a mortality risk factor able to highlight critical hypoxic damage. Using a ΔOER ≥ 40% could be clinically applicable to characterise the most fragile patients.
A Framework of Analysis to Facilitate the Harmonization of Multicenter Radiomic Features in Prostate Cancer
Authors: Castaldo Rossana , Brancato Valentina , Cavaliere Carlo , Trama Francesco , Illiano Ester , Costantini Elisabetta , Ragozzino Alfonso , Salvatore Marco , Nicolai Emanuele , Franzese Monica
Published: December 2022

Pooling radiomic features coming from different centers in a statistical framework is challenging due to the variability in scanner models, acquisition protocols, and reconstruction settings. To remove technical variability, commonly called batch effects, different statistical harmonization strategies have been widely used in genomics but less considered in radiomics. The aim of this work was to develop a framework of analysis to facilitate the harmonization of multicenter radiomic features extracted from prostate T2-weighted magnetic resonance imaging (MRI) and to improve the power of radiomics for prostate cancer (PCa) management in order to develop robust non-invasive biomarkers translating into clinical practice. To remove technical variability and correct for batch effects, we investigated four different statistical methods (ComBat, SVA, Arsynseq, and mixed effect). The proposed approaches were evaluated using a dataset of 210 prostate cancer (PCa) patients from two centers. The impacts of the different statistical approaches were evaluated by principal component analysis and classification methods (LogitBoost, random forest, K-nearest neighbors, and decision tree). The ComBat method outperformed all other methods by achieving 70% accuracy and 78% AUC with the random forest method to automatically classify patients affected by PCa. The proposed statistical framework enabled us to define and develop a standardized pipeline of analysis to harmonize multicenter T2W radiomic features, yielding great promise to support PCa clinical practice.
Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus
Authors: Gorgojo-Martínez Juan J. , Mezquita-Raya Pedro , Carretero-Gómez Juana , Castro Almudena , Cebrián-Cuenca Ana , de Torres-Sánchez Alejandra , García-de-Lucas María Dolores , Núñez Julio , Obaya Juan Carlos , Soler María José , Górriz José Luis , Rubio-Herrera Miguel Ángel
Published: December 2022

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated in type 2 diabetes and obesity for their high efficacy in controlling glycaemia and inducing body weight loss, respectively. Patients may develop gastrointestinal adverse events (GI AEs), namely nausea, vomiting, diarrhoea and/or constipation. To minimize their severity and duration, healthcare providers (HCPs) and patients must be aware of appropriate measures to follow while undergoing treatment. An expert panel comprising endocrinologists, nephrologists, primary care physicians, cardiologists, internists and diabetes nurse educators convened across virtual meetings to reach a consensus regarding these compelling recommendations. Firstly, specific guidelines are provided about how to reach the maintenance dose and how to proceed if GI AEs develop during dose-escalation. Secondly, specific directions are set about how to avoid/minimize nausea, vomiting, diarrhoea and constipation symptoms. Clinical scenarios representing common situations in daily practice, and infographics useful to guide both HCPs and patients, are included. These recommendations may prevent people with T2D and/or obesity from withdrawing from GLP-1 RAs treatment, thus benefitting from their superior effect on glycaemic control and weight loss.
Real Time Intrarenal Pressure Control during Flexible Ureterorrenscopy Using a Vascular PressureWire: Pilot Study
Authors: Sierra Alba , Corrales Mariela , Kolvatzis Merkourios , Doizi Steeve , Traxer Olivier
Published: December 2022

(1) Introduction: To evaluate the feasibility of measuring the intrapelvic pressure (IPP) during flexible ureterorenoscopy (f-URS) with a PressureWire and to optimize safety by assessing IPP during surgery. (2) Methods: Patients undergoing f-URS for different treatments were recruited. A PressureWire (0.014”, St. Jude Medical, Little Canada, MN, USA) was placed into the renal cavities to measure IPP. Gravity irrigation at 40 cmH2O over the patient and a hand-assisted irrigation system were used. Pressures were monitored in real time and recorded for analysis. Fluid balance and postoperative urinary tract infection (UTI) were documented. (3) Results: Twenty patients undergoing f-URS were included with successful IPP monitoring. The median baseline IPP was 13.6 (6.8–47.6) cmH2O. After the placement of the UAS, the median IPP was 17 (8–44.6) cmH2O. With irrigation pressure set at 40 cmH2O without forced irrigation, the median IPP was 34 (19–81.6) cmH2O. Median IPP during laser lithotripsy, with and without the use of on-demand forced irrigation, was 61.2 (27.2–149.5) cmH2O. The maximum pressure peaks recorded during forced irrigation ranged from 54.4 to 236.6 cmH2O. After the surgery, 3 patients (15%) presented UTI; 2 of them had a positive preoperative urine culture, previously treated, and a positive fluid balance observed after the surgery. (4) Conclusion: Based on our experience, continuous monitoring of IPP with a wire is easy to reproduce, effective, and safe. In addition, it allows us to identify and avoid high IPPs, which may affect surgery-related complications.
Predictors of Clinically Significant Prostate Cancer in Patients with PIRADS Categories 3–5 Undergoing Magnetic Resonance Imaging-Ultrasound Fusion Biopsy of the Prostate
Authors: Szempliński Stanisław , Kamecki Hubert , Dębowska Małgorzata , Zagożdżon Bartłomiej , Mokrzyś Mateusz , Zawadzki Marek , Sosnowski Roman , Tokarczyk Andrzej , Poletajew Sławomir , Kryst Piotr , Nyk Łukasz
Published: December 2022

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.