bluuebunny/crossref_metadata_2025 huggingface dataset:
Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway
Authors: Tonolo Federica , Folda Alessandra , Scalcon Valeria , Marin Oriano , Bindoli Alberto , Rigobello Maria Pia
Published: April 2022

Redox status and inflammation are related to the pathogenesis of the majority of diseases. Therefore, understanding the role of specific food-derived molecules in the regulation of their specific pathways is a relevant issue. Our previous studies indicated that K-8-K and S-10-S, milk and soy-derived bioactive peptides, respectively, exert antioxidant effects through activation of the Keap1/Nrf2 pathway. A crosstalk between Nrf2 and NF-κB, mediated by the action of heme oxygenase (HO-1), is well known. On this basis, we studied if these peptides, in addition to their antioxidant activity, could exert anti-inflammatory effects in human cells. First, we observed an increase of HO-1 expression in Caco-2 cells treated with K-8-K and S-10-S, following the activation of the Keap1/Nrf2 pathway. Moreover, when cells are treated with the two peptides and stimulated by TNF-α, the levels of NF-κB in the nucleus decreased in comparison with TNF-α alone. In the same conditions, we observed the downregulation of the gene expression of proinflammatory cytokines (IL1B, IL6, and TNF), while the anti-inflammatory cytokine gene, IL1RN, was upregulated in Caco-2 cells processed as reported above. Then, when the cells were pretreated with the two peptides and stimulated with LPS, a different proinflammatory factor, (TNF-α) was estimated to have a lower secretion in the supernatant of cells. In conclusion, these observations confirmed that Nrf2-activating bioactive peptides, K-8-K and S-10-S, exerted anti-inflammatory effects by inhibiting the NF-κB pathway.
The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
Authors: Leysen Hanne , Walter Deborah , Clauwaert Lore , Hellemans Lieselot , van Gastel Jaana , Vasudevan Lakshmi , Martin Bronwen , Maudsley Stuart
Published: April 2022

During the aging process our body becomes less well equipped to deal with cellular stress, resulting in an increase in unrepaired damage. This causes varying degrees of impaired functionality and an increased risk of mortality. One of the most effective anti-aging strategies involves interventions that combine simultaneous glucometabolic support with augmented DNA damage protection/repair. Thus, it seems prudent to develop therapeutic strategies that target this combinatorial approach. Studies have shown that the ADP-ribosylation factor (ARF) GTPase activating protein GIT2 (GIT2) acts as a keystone protein in the aging process. GIT2 can control both DNA repair and glucose metabolism. Through in vivo co-regulation analyses it was found that GIT2 forms a close coexpression-based relationship with the relaxin-3 receptor (RXFP3). Cellular RXFP3 expression is directly affected by DNA damage and oxidative stress. Overexpression or stimulation of this receptor, by its endogenous ligand relaxin 3 (RLN3), can regulate the DNA damage response and repair processes. Interestingly, RLN3 is an insulin-like peptide and has been shown to control multiple disease processes linked to aging mechanisms, e.g., anxiety, depression, memory dysfunction, appetite, and anti-apoptotic mechanisms. Here we discuss the molecular mechanisms underlying the various roles of RXFP3/RLN3 signaling in aging and age-related disorders.
Characterization of Stem Nodes Associated with Carbon Partitioning in Maize in Response to Nitrogen Availability
Authors: Zhao Yujing , Ning Peng , Feng Xiaojie , Ren Hanshuo , Cui Mingtang , Yang Lu
Published: April 2022

Stem node has been found to be a hub for controlling mineral nutrient distribution in gramineous plants. However, the characteristics of stem nodes associated with whole-plant carbon partitioning in maize (Zea mays L.) and their responses to nitrogen (N) availability remains elusive. Maize plants were grown in greenhouse under low to high N supply. Plant growth, sugar accumulation, and sugar transporters in nodes and leaves, as well as the anatomical structure of nodes, were investigated at vegetative phase. When compared to N-sufficient plants, low-N availability stunted growth and resulted in 49–64% less sugars in leaves, which was attributed to low photosynthesis or the accelerated carbon export, as evidenced by more 13C detected further below leaf tips. Invariably higher sugar concentrations were found in the stem nodes, rather than in the leaves across N treatments, indicating a crucial role of nodes in facilitating whole-plant carbon partitioning. More and smaller vascular bundles and phloem were observed in stem nodes of N-deficient plants, while higher sugar levels were found in the bottom nodes than in the upper ones. Low-N availability upregulated the gene expressions of sugar transporters, which putatively function in nodes such as ZmSWEETs and ZmSUTs at the bottom stem, but suppressed them in the upper ones, showing a developmental impact on node function. Further, greater activity of sugar transporters in the bottom nodes was associated with less sugars in leaves. Overall, these results highlighted that stem nodes may play an important role in facilitating long-distance sugar transport in maize.
Changing Landscape of Cancer Vaccines—Novel Proteomics Platform for New Antigen Compositions
Authors: Lokhov Petr G. , Lichtenberg Steven , Balashova Elena E.
Published: April 2022

The creation of cancer vaccines is a constant priority for research and biotechnology. Therefore, the emergence of any new technology in this field is a significant event, especially because previous technologies have not yielded results. Recently, the development of a cancer vaccine has been complemented by a new proteomics technology platform that allows the creation of antigen compositions known as antigenic essences. Antigenic essence comprises a target fraction of cellular antigens, the composition of which is precisely controlled by peptide mass spectrometry and compared to the proteomic footprint of the target cells to ensure similarity. This proteomics platform offers potential for a massive upgrade of conventional cellular cancer vaccines. Antigenic essences have the same mechanism of action, but without the disadvantages, and with notable advantages such as precise targeting of the immune response, safety, controlled composition, improved immunogenicity, addressed MHC restriction, and extended range of vaccination doses. The present paper calls attention to this novel platform, stimulates discussion of the role of antigenic essence in vaccine development, and consolidates academic science with biotech capabilities. A brief description of the platform, list of cellular cancer vaccines suitable for the upgrade, main recommendations, limitations, and legal and ethical aspects of vaccine upgrade are reported here.
Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain
Authors: Della Pietra Adriana , Savinainen Juha , Giniatullin Rashid
Published: April 2022

Migraine is a disabling neurovascular disorder characterized by severe pain with still limited efficient treatments. Endocannabinoids, the endogenous painkillers, emerged, alternative to plant cannabis, as promising analgesics against migraine pain. In this thematic review, we discuss how inhibition of the main endocannabinoid-degrading enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), could raise the level of endocannabinoids (endoCBs) such as 2-AG and anandamide in order to alleviate migraine pain. We describe here: (i) migraine pain signaling pathways, which could serve as specific targets for antinociception; (ii) a divergent distribution of MAGL and FAAH activities in the key regions of the PNS and CNS implicated in migraine pain signaling; (iii) a complexity of anti-nociceptive effects of endoCBs mediated by cannabinoid receptors and through a direct modulation of ion channels in nociceptive neurons; and (iv) the spectrum of emerging potent MAGL and FAAH inhibitors which efficiently increase endoCBs levels. The specific distribution and homeostasis of endoCBs in the main regions of the nociceptive system and their generation ‘on demand’, along with recent availability of MAGL and FAAH inhibitors suggest new perspectives for endoCBs-mediated analgesia in migraine pain.
Genome-Wide Identification and Characterisation of Wheat MATE Genes Reveals Their Roles in Aluminium Tolerance
Authors: Duan Wenjing , Lu Fengkun , Cui Yue , Zhang Junwei , Du Xuan , Hu Yingkao , Yan Yueming
Published: April 2022

The Multidrug and toxin efflux (MATE) gene family plays crucial roles in plant growth and development and response to adverse stresses. This work investigated the structural and evolutionary characteristics, expression profiling and potential functions involved in aluminium (Al) tolerance from a genome-wide level. In total, 211 wheat MATE genes were identified, which were classified into four subfamilies and unevenly distributed on chromosomes. Duplication analysis showed that fragments and tandem repeats played the main roles in the amplification of TaMATEs, and Type II functional disproportionation had a leading role in the differentiation of TaMATEs. TaMATEs had abundant Al resistance and environmental stress-related elements, and generally had a high expression level in roots and leaves and in response to Al stress. The 3D structure prediction by AlphaFold and molecular docking showed that six TaMATE proteins localised in the plasmalemma could combine with citrate via amino acids in the citrate exuding motif and other sites, and then transport citrate to soil to form citrate aluminium. Meanwhile, citrate aluminium formed in root cells might be transported to leaves by TaMATEs to deposit in vacuoles, thereby alleviating Al toxicity.
Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers
Authors: Evrard Camille , Messina Stéphane , Sefrioui David , Frouin Éric , Auriault Marie-Luce , Chautard Romain , Zaanan Aziz , Jaffrelot Marion , De La Fouchardière Christelle , Aparicio Thomas , Coriat Romain , Godet Julie , Silvain Christine , Randrian Violaine , Sabourin Jean-Christophe , Guimbaud Rosine , Miquelestorena-Standley Elodie , Lecomte Thierry , Moulin Valérie , Karayan-Tapon Lucie , Tachon Gaëlle , Tougeron David
Published: April 2022

Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.
Dioscin Alleviates Cisplatin-Induced Mucositis in Rats by Modulating Gut Microbiota, Enhancing Intestinal Barrier Function and Attenuating TLR4/NF-κB Signaling Cascade
Authors: Jin Shengzi , Guan Tongxu , Wang Shuang , Hu Mengxin , Liu Xingyao , Huang Siqi , Liu Yun
Published: April 2022

Cisplatin-based chemotherapy causes intestinal mucositis, which causes patients immense suffering and hinders the process of cancer treatment. Dioscin is a natural steroid saponin that exhibits strong anti-inflammatory and immunomodulatory properties. Herein, we investigate the protective effect of dioscin on cisplatin induced mucositis in rats from the perspective of gut microbiota and intestinal barrier. We established a rat model of intestinal mucositis by tail vein injection of cisplatin, and concurrently treated with dioscin oral administration. Parameters, such as body weight, diarrheal incidence, and D-Lactate levels, were assessed in order to evaluate the effects of dioscin on intestinal mucositis in rats. Furthermore, biological samples were collected for microscopic gut microbiota, intestinal integrity, and immune inflammation analyses to elucidate the protective mechanisms of dioscin on intestinal mucositis. The results revealed that administration of dioscin significantly attenuated clinical manifestations, histological injury and inflammation in mucositis rats. Besides this, dioscin markedly inhibited the gut microbiota dysbiosis induced by cisplatin. Meanwhile, dioscin partially alleviated junctions between ileum epithelial cells and increased mucus secretion. Moreover, dioscin effectively inhibited the TLR4-MyD88-NF-κB signal transduction pathway and reduced the secretion of subsequent inflammatory mediators. These results suggested that dioscin effectively attenuated cisplatin-induced mucositis in part by modulating the gut microflora profile, maintaining ileum integrity and inhibiting the inflammatory response through the TLR4-MyD88-NF-κB pathway.
COVID-19 Pandemic-Related Impacts on Newborn Screening Public Health Surveillance
Authors: Singh Sikha , Caggana Michele , Johnson Carol , Lee Rachel , Zarbalian Guisou , Gaviglio Amy , Keehn Alisha , Morrison Mia , Becker Scott J. , Ojodu Jelili
Published: April 2022

Newborn screening (NBS) is an essential public health service that performs screening to identify those newborns at increased risk for a panel of disorders, most of which are genetic. The goal of screening is to link those newborns at the highest risk to timely intervention and potentially life-saving treatment. The global COVID-19 pandemic led to disruptions within the United States public health system, revealing implications for the continuity of newborn screening laboratories and follow-up operations. The impacts of COVID-19 across different states at various time points meant that NBS programs impacted by the pandemic later could benefit from the immediate experiences of the earlier impacted programs. This article will review the collection, analysis, and dissemination of information during the COVID-19 pandemic facilitated by a national, centralized technical assistance and resource center for NBS programs.
A Case Report of Severe Factor XI Deficiency during Cardiac Surgery: Less Can Be More
Authors: Kazui Toshinobu , Nielsen Vance G. , Audie Spencer D. , Venkataramani Rajagopalan M. , Bryant John T. , Swenson Kristin , Ford Paul M.
Published: April 2022

Severe congenital Factor XI (FXI) deficiency (<20% normal activity) can be associated with significant bleeding disorders, and there has been great concern for severe bleeding following cardiac surgery requiring cardiopulmonary bypass (CPB) in this patient population. Over the past four decades remarkably different approaches to this problem have been taken, including the administration of blood volumes of fresh frozen plasma, administration of activated recombinant Factor VII, and diminutive administration of heparin. We describe a case wherein the patient was assessed in the perioperative period with a point-of-care, viscoelastic hemostasis device (ROTEM), with changes in the intrinsic/Factor XII-dependent coagulation pathway determined before, during, and after CPB. Fresh frozen plasma was administered in small amounts (5–7.5 mL/kg) just before surgery began and just before cessation of CPB. Administering fresh frozen plasma to the patient to nearly normalize in vitro ROTEM hemostasis values at times when hemostasis was needed resulted in no important bleeding occurring or need of further transfusion of other blood products. In conclusion, by using small amounts of fresh frozen plasma guided by ROTEM, an evidenced-based, precision medicine approach resulted in optimized patient care and outcome.
Noninvasive Evaluation of Intraventricular Flow Dynamics by the HyperDoppler Technique: First Application to Normal Subjects, Athletes, and Patients with Heart Failure
Authors: Fiorencis Andrea , Pepe Marco , Smarrazzo Vittorio , Martini Marika , Severino Salvatore , Pergola Valeria , Evangelista Marco , Incarnato Pierluigi , Previtero Marco , Maglione Marco , Iliceto Sabino , Pedrizzetti Gianni , Mele Donato
Published: April 2022

Background: HyperDoppler is a new echocardiographic color Doppler-based technique that can assess intracardiac flow dynamics. The aim of this study was to verify the feasibility and reproducibility of this technique in unselected patients and its capability to differentiate measures of vortex flow within the left ventricle (LV) in normal sedentary subjects, athletes, and patients with heart failure. Methods: Two hundred unselected, consecutive patients presenting at the echocardiographic laboratory, 50 normal subjects, 30 athletes, and 50 patients with chronic heart failure and LV ejection fraction <50% were enrolled. Images were acquired using a MyLab X8 echo-scanner. Area, intensity, depth, length, and kinetic energy dissipation (KED) of vortex flow were measured. Results: The HyperDoppler technique feasibility was 94.5%. According to the intraclass correlation coefficient evaluations, repeatability and reproducibility of vortex flow measures were good for vortex area (0.82, 0.85), length (0.83, 0.82), and depth (0.87, 0.84) and excellent for intensity (0.92, 0.90) and KED (0.98, 0.98). Combining different vortex flow measures, the LV flow profile of healthy sedentary individuals, athletes, and heart failure patients could be differentiated. Conclusions: HyperDoppler is a feasible, reliable, and practical technique for the assessment of LV flow dynamics and may distinguish normal subjects and patients with heart failure.
Use of Vaginal Dinoprostone (PGE2) in Patients with Premature Rupture of Membranes (PROM) Undergoing Induction of Labor: A Comparative Study
Authors: López-Jiménez Nuria , García-Sánchez Fiamma , Pailos Rafael Hernández , Rodrigo-Álvaro Valentin , Pascual-Pedreño Ana , Moreno-Cid María , Hernández-Martínez Antonio , Molina-Alarcón Milagros
Published: April 2022

Purpose: To evaluate the effect and safety of vaginal dinoprostone in pregnant women with PROM who undergo induction of labor (IoL). Materials and Methods: Prospective observational study conducted at La Mancha Centro hospital from 1 February 2019, to 30 August 2020. Obstetric and neonatal variables of 94 pregnant women with PROM who underwent IoL with vaginal dinoprostone were analyzed, and the results were compared with 330 patients without PROM who also underwent IoL. Bivariate and multivariate analyses were performed using binary and multiple linear regression. Results: A total of 424 women were included in this study. A greater response to cervical ripening (Bishop score > 6) with PGE2 was observed in the PROM group (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.50–4.99, p = 0.001), as well as a shorter total duration of IoL (mean difference (MD) 2823.37 min (min), 95% CI 1257.30–4389.43, p < 0.001). Cesarean sections were performed in 28.7% (n = 27) of patients in the PROM group vs. 34.2% (n = 113) of patients in the non-PROM group, with no significant differences (OR 0.87%, 95% CI 0.47–1.60, p = 0.652). There were no significant differences in changes in the cardiotocographic record (CTG), postpartum hemorrhage (PPH), uterine rupture, or adverse neonatal outcomes between the two groups. Conclusions: The use of vaginal dinoprostone in pregnant women undergoing IoL with PROM is safe for the mother and the fetus, shortens the total delivery time, and does not increase the risk of cesarean section compared with pregnant women undergoing IoL without PROM.
Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?
Authors: Wysocka-Mincewicz Marta , Groszek Artur , Ambrozkiewicz Filip , Paziewska Agnieszka , Dąbrowska Michalina , Rybak Anna , Konopka Ewa , Ochocińska Agnieszka , Żeber-Lubecka Natalia , Karczmarski Jakub , Bierła Joanna B. , Trojanowska Ilona , Rogowska Agnieszka , Ostrowski Jerzy , Cukrowska Bożena
Published: April 2022

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700–0.7690) in comparison with 0.664 (95% CI: 0.632–0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.
Non-Invasive Assessment of Arterial Stiffness: Pulse Wave Velocity, Pulse Wave Analysis and Carotid Cross-Sectional Distensibility: Comparison between Methods
Authors: Salvi Paolo , Valbusa Filippo , Kearney-Schwartz Anna , Labat Carlos , Grillo Andrea , Parati Gianfranco , Benetos Athanase
Published: April 2022

Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid–femoral and carotid–radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid–femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid–femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid–radial PWV. Conclusions: This study showed a close correlation between carotid–femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.
Influence of the Cumulative Incidence of COVID-19 Cases on the Mental Health of the Spanish Out-of-Hospital Professionals
Authors: Soto-Cámara Raúl , Navalpotro-Pascual Susana , Jiménez-Alegre José Julio , García-Santa-Basilia Noemí , Onrubia-Baticón Henar , Navalpotro-Pascual José M. , Thuissard Israel John , Fernández-Domínguez Juan José , Matellán-Hernández María Paz , Pastor-Benito Elena , Polo-Portes Carlos Eduardo , Cárdaba-García Rosa M. ,   on behalf of the IMPSYCOVID-19 Study Group
Published: April 2022

This study aimed to analyze the psychological affectation of health professionals (HPs) of Spanish Emergency Medical Services (EMSs) according to the cumulative incidence (CI) of COVID-19 cases in the regions in which they worked. A cross-sectional descriptive study was designed, including all HPs working in any EMS of the Spanish geography between 1 February 2021 and 30 April 2021. Their level of stress, anxiety and depression (DASS-21) and the perception of self-efficacy (G-SES) were the study’s main results. A 2-factor analysis of covariance was used to determine if the CI regions of COVID-19 cases determined the psychological impact on each of the studied variables. A total of 1710 HPs were included. A third presented psychological impairment classified as severe. The interaction of CI regions with the studied variables did not influence their levels of stress, anxiety, depression or self-efficacy. Women, younger HPs or those with less EMS work experience, emergency medical technicians (EMT), workers who had to modify their working conditions or those who lived with minors or dependents suffered a greater impact from the COVID-19 pandemic in certain regions. These HPs have shown high levels of stress, anxiety, depression and medium levels of self-efficacy, with similar data in the different geographical areas. Psychological support is essential to mitigate their suffering and teach them to react to adverse events.
Biventricular Myocardial Strain Analysis in Patients with Pulmonary Arterial Hypertension Using Cardiac Magnetic Resonance Tissue-Tracking Technology
Authors: Cao Jibin , Li Simiao , Cui Lingling , Zhu Kexin , Huo Huaibi , Liu Ting
Published: April 2022

To evaluate both left and right ventricular (LV and RV) function in patients with pulmonary arterial hypertension (PAH) using cardiac magnetic resonance tissue-tracking (CMR-TT) technology and explore its clinical value. Methods: A total of 79 participants (including 47 patients with PAH and 32 healthy controls) underwent cardiac magnetic resonance imaging (CMRI) with a short-axis balanced steady-state free precession (SSFP) sequence. The biventricular cardiac function parameters and strain parameters were obtained by postprocessing with CVI42 software. A comparative analysis was performed between the LV and RV strain parameters in all PAH patients and in PAH patients with reduced or preserved cardiac function. Results: The results showed preferable repeatability of CMR-TT in analyzing the global radial strain (GRS), circumferential strain (GCS), and longitudinal strain (GLS) of the left and right ventricles in the PAH group. The GRS, GCS, and GLS of the left and right ventricles except for LV GRS (LVGRS) of PAH patients were significantly lower than those of healthy controls (p < 0.05 for all). The GRS and GCS of the left and right ventricles showed a moderate correlation in the PAH group (r = 0.323, p = 0.02; r = 0.301, p = 0.04, respectively). PAH patients with preserved RV function (n = 9) showed significantly decreased global and segmental RS, CS, and LS of the right ventricles than healthy controls (p < 0.05 for all), except for basal RVGCS (RVGCS-b, p = 0.996). Only the LVGLS was significantly different between the PAH patients with preserved LV function (n = 32) and the healthy controls (−14.23 ± 3.01% vs. −16.79 ± 2.86%, p < 0.01). Conclusions: As a nonradioactive and noninvasive technique, CMR-TT has preferable feasibility and repeatability in quantitatively evaluating LV and RV strain parameters in PAH patients and can be used to effectively detect early biventricular myocardial damage in patients with PAH.
Positivity Trends of Bacterial Cultures from Cases of Acute and Chronic Periprosthetic Joint Infections
Authors: Birlutiu Rares Mircea , Stoica Cristian Ioan , Russu Octav , Cismasiu Razvan Silviu , Birlutiu Victoria
Published: April 2022

Background: There is no clear distinction in the literature regarding the positivity trends of bacterial cultures in acute and chronic prosthetic joint infections. Methods: We prospectively included in this study all consecutive patients, aged over 18 years, that were hospitalized from September 2016 through December 2019, that underwent a joint arthroplasty revision surgery. Results: Forty patients were included in our analysis, 11 acute/acute hematogenous and 29 chronic PJIs. We were able to identify all strains of acute/acute hematogenous PJIs within 3 days, whereas this took 8 days for chronic PJIs. Sonication fluid cultures increased the positivity rate and helped in identifying rare pathogens such as Ralstonia pickettii from chronic PJIs, but also increased the number of identified strains from acute PJIs. Culturing synovial fluid in our study did not seem to have a clear benefit compared to sonication fluid and periprosthetic tissue cultures. Conclusion: There was a different positivity trend in bacterial cultures. Empiric broad-spectrum antibiotic therapy can be re-evaluated after 3 days for acute PJIs. A prolonged incubation time, especially in the case of chronic PJIs, is mandatory; however, extending the incubation period beyond 14 days would not further improve the ability to identify microorganisms.
Long-Term Outcomes of Targeted Therapy after First-Line Immunotherapy in BRAF-Mutated Advanced Cutaneous Melanoma Patients—Real-World Evidence
Authors: Rogala Paweł , Czarnecka Anna M. , Cybulska-Stopa Bożena , Ostaszewski Krzysztof , Piejko Karolina , Ziętek Marcin , Dziura Robert , Rutkowska Ewa , Galus Łukasz , Kempa-Kamińska Natasza , Calik Jacek , Sałek-Zań Agata , Zemełka Tomasz , Bal Wiesław , Kamycka Agnieszka , Świtaj Tomasz , Kamińska-Winciorek Grażyna , Suwiński Rafał , Mackiewicz Jacek , Rutkowski Piotr
Published: April 2022

Background: Currently, limited data on targeted therapy and immunotherapy sequencing in patients with BRAF-mutant melanoma is available. Targeted therapy and immunotherapy are expected to be comparable in terms of overall survival (OS) when used as second-line therapies; therefore, understanding the characteristics of patients who completed sequential treatment is needed. Methods: The primary objective of this study was to analyze the efficacy of BRAFi/MEKi activity as second-line therapy in patients with advanced melanoma. We also aimed to describe the clinical characteristics of patients with advanced melanoma who were treated sequentially with immunotherapy and targeted therapy. We enrolled 97 patients treated between 1st December 2015 and 31st December 2020 with first-line immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors; and for the second-line treatment with at least one cycle of BRAFi/MEKi therapy with follow-up through 31 January 2022. Results: Median OS since first-line treatment initiation was 19.9 months and 12.8 months since initiation of BRAFi/MEKi treatment. All BRAFi/MRKi combinations were similarly effective. Median progression free survival (PFS) was 7.5 months since initiation of any BRAFi/MEKi treatment. Conclusions: BRAFi/MEKi therapy is effective in the second-line in advanced and metastatic melanoma patients. For the first time, the efficacy of all BRAFi/MEKi combinations as second-line therapy is shown.
Criteria for Return-to-Play (RTP) after Rotator Cuff Surgery: A Systematic Review of Literature
Authors: Bravi Marco , Fossati Chiara , Giombini Arrigo , Macaluso Andrea , Lazzoli José Kawazoe , Santacaterina Fabio , Bressi Federica , Vorini Ferruccio , Campi Stefano , Papalia Rocco , Pigozzi Fabio
Published: April 2022

This systematic review of the literature aimed to highlight which criteria are described in the literature to define when a patient, after rotator cuff repair (RCR), is ready for return-to-play (RTP), which includes return to unrestricted activities, return to work, leisure, and sport activities. An online systematic search on the US National Library of Medicine (PubMed/MEDLINE), SCOPUS, Web of Science (WOS), and the Cochrane Database of Systematic Reviews, was performed with no data limit until December 2021. A total of 24 studies that reported at least one criterion after RCR were included. Nine criteria were identified and among these, the most reported criterion was the time from surgery, which was used by 78% of the studies; time from surgery was used as the only criterion by 54% of the studies, and in combination with other criteria, in 24% of the studies. Strength and ROM were the most reported criteria after time (25%). These results are in line with a previous systematic review that aimed to identify RTP criteria after surgical shoulder stabilization and with a recent scoping review that investigated RTP criteria among athletes after RCR and anterior shoulder stabilization. Compared to this latest scoping review, our study adds the methodological strength of being conducted according to the Prisma guidelines; furthermore, our study included both athletes and non-athletes to provide a comprehensive view of the criteria used after RCR; moreover, ten additional recent manuscripts were examined with respect to the scoping review.
Real-World Data of Trastuzumab Deruxtecan for Advanced Gastric Cancer: A Multi-Institutional Retrospective Study
Authors: Matsumoto Toshihiko , Yamamura Shogo , Ikoma Tatsuki , Kurioka Yusuke , Doi Keitaro , Boku Shogen , Shibata Nobuhiro , Nagai Hiroki , Shimada Takanobu , Tsuduki Takao , Tsumura Takehiko , Takatani Masahiro , Yasui Hisateru , Satake Hironaga
Published: April 2022

Trastuzumab deruxtecan (T-DXd) has shown promising efficacy against HER2-positive advanced gastric cancer (AGC). However, data on its real-world efficacy in AGC patients are insufficient, and the predictive marker of T-DXd is unclear. In this multi-center retrospective study, we collected clinical information of 18 patients with HER2-positive AGC who received T-DXd after intolerant or refractory responses to at least two prior regimens and analyzed predictive factors. The median age was 71 years (range: 51–85), 13 men were included, and ECOG performance status (PS): 0/1/2/3 was 9/6/2/1. A total of 11 patients (61%) received prior immune checkpoint inhibitors (ICIs), 14 patients were HER2 3+, and 4 patients were HER2 2+/FISH positive. The median trastuzumab (Tmab)-free interval was 7.7 months (range: 2.8–28.6). The overall response rate was 41%, and the disease control rate was 76%. Median progression-free survival (PFS) was 3.9 months (95% CI: 2.6–6.5), and median overall survival (OS) was 6.1 months (95% CI: 3.7–9.4). PFS (6.5 vs. 2.9 months, p = 0.0292) and OS (9.2 vs. 3.7 months, p = 0.0819) were longer in patients who received prior ICIs than in those who had not. PFS (6.5 vs. 3.4 months, p = 0.0249) and OS (9.4 vs. 5.7 months, p = 0.0426) were longer in patients with an 8 month or longer Tmab-free interval. In patients with ascites, PFS (6.5 vs. 2.75 months, p = 0.0139) and OS (9.4 vs. 3.9 months, p = 0.0460) were shorter. T-DXd showed promising efficacy in HER2-positive AGC patients in a real-world setting. Pre-administration of ICIs and a sufficient Tmab-free interval may be predictive factors of T-DXd efficacy.
Deformation Heating and Temperature Changes in a Near-β Titanium Alloy during β-Processed Forging
Authors: Kitashima Tomonori , Meng Lingjian
Published: April 2022

We investigated the temperature increase caused by heat generation from plastic deformation during β-processed forging in a near-β titanium alloy, Ti-17 alloy (Ti-5Al-2Sn-2Zr-4Cr-4Mo, wt%), by inserting thermocouples into large workpieces (100 mm in diameter and 50 mm in height). The workpiece was initially heated and held at 1193 K (920 °C) in the single-β region. It was subsequently forged between hot dies in surrounding heaters at a compression percentage of 75% at strain rates of 0.05 and 0.5 s−1 at 1023–1123 K in the (α + β) region. At 0.05 s−1, the temperature logarithmically increased by 39 K in 28 s for 1023 K; it increased by 30 K in 28 s for 1073 K. However, at 0.5 s−1, the material temperature increased, in 3 s, beyond or close to the β-transus temperature during forging at 1023 and 1073 K. In addition, as the forging temperature decreased, the increase in material temperature moderated, resulting in a difference of 27 K in the last forging stage, between the conditions of 1023 and 1073 K. This would reduce the temperature difference effect on microstructure formation during β-processed forging.
Enhanced Abrasion Resistance of Spark Plasma Sintered and HVOF Sprayed Hadfield High Manganese Steel by Turning and Diamond Smoothing
Authors: Lindner Thomas , Liborius Hendrik , Preuß Bianca , Hanisch Niclas , Schubert Andreas , Lampke Thomas
Published: April 2022

Austenitic high-manganese steels (HMnS) offer very high wear resistance under dynamic loading due to their high work hardening capacity. However, resistance to static abrasive loading is limited. Various approaches to increasing abrasion resistance are known from traditionally manufactured metallurgical components. These confirm the high potential for surface protection applications. In this work, the powder of the Hadfield HMnS X120Mn12 is prepared and processed by high-velocity oxy-fuel (HVOF) spraying and spark-plasma sintering (SPS). A good correlation was observed between the results of the HVOF and SPS specimen. Different surface conditions of the coatings and the sintered specimens were prepared by machining. Compared to the polished state, turning and diamond smoothing can increase the surface hardness from 220 HV to over 700 HV significantly. Regardless of the surface finish condition, similar good wear resistance can be demonstrated due to strong work hardening under sliding and reciprocating wear loading. In contrast, the finish machining process clearly influences abrasion resistance in the scratch test with the best results for the diamond smoothed condition. Especially against the background of current trends toward alternative coating systems, the presented results offer a promising approach for the development of HMnS in the field of coating technology.
Current Landscape of Coccidioidomycosis
Authors: Boro Ryan , Iyer Prema C. , Walczak Maciej A.
Published: April 2022

Coccidioidomycosis, also known as Valley fever, is an endemic fungal infection commonly found in the southwestern parts of the United States. However, the disease has seen an increase in both in its area of residency and its prevalence. This review compiles some of the latest information on the epidemiology, current and in-development pharmaceutical approaches to treat the disease, trends and projections, diagnostic concerns, and the overlapping dynamics of coccidioidomycosis and COVID-19, including in special populations. This review provides an overview of the current diagnostic and therapeutic strategies and identifies areas of future development.
Clinical Implications of Glyoxalase1 Gene Polymorphism and Elevated Levels of the Reactive Metabolite Methylglyoxal in the Susceptibility of Type 2 Diabetes Mellitus in the Patients from Asir and Tabuk Regions of Saudi Arabia
Authors: Alhujaily Muhanad , Mir Mohammad Muzaffar , Mir Rashid , Alghamdi Mushabab Ayed Abdullah , Wani Javed Iqbal , Sabah Zia ul , Elfaki Imadeldin , Alnour Tarig Mohammad Saad , Jeelani Mohammed , Abomughaid Mosleh Mohammad , Alharbi Samir Abdulkarim
Published: April 2022

Diabetes mellitus constitutes a big challenge to the global health care system due to its socioeconomic impacts and very serious complications. The incidence and the prevalence rate are increased in the Gulf region including the KSA. Type 2 diabetes mellitus (T2DM) is caused by diverse risk factors including obesity, unhealthy dietary habits, physical inactivity, smoking and genetic factors. The molecular genetic studies have helped in the detection of many single nucleotide polymorphisms (SNP) with different diseases including cancers, cardiovascular diseases and T2DM. The glyoxalase 1 (GLO1) is a detoxifying enzyme and catalyzes the elimination of the cytotoxic product methylglyoxal (MG) by converting it to D-lactate, which is not toxic to tissues. MG accumulation is associated with the pathogenesis of different diseases including T2DM. In this study, we have investigated the association of the glyoxalase 1 SNPs (rs2736654) rs4746 C>A and rs1130534 T>A with T2DM using the amplification refractory mutation system PCR. We also measured the concentration of MG by ELISA in T2DM patients and matched heathy controls. Results show that the CA genotype of the GLO rs4647 A>C was associated with T2DM with OR = 2.57, p-value 0.0008 and the C allele was also associated with increased risk to T2DM with OR = 2.24, p-value = 0.0001. It was also observed that AT genotype of the rs1130534 was associated with decreased susceptibility to T2DM with OR = 0.3, p-value = 0.02. The A allele of rs1130534 was also associated with reduced risk to T2DM with PR = 0.27 = 0.006. In addition, our ELISA results demonstrate significantly increased MG concentrations in serum of the T2DM patients. We conclude that the GLO1 SNP may be associated with decreased enzyme activity and a resultant susceptibility to T2DM. Further well-designed studies in different and large patient populations are recommended to verify these findings.
Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis
Authors: Mikhaylenko Dmitry S. , Kuznetsova Ekaterina B. , Musatova Viktoria V. , Bure Irina V. , Deryagina Tatiana A. , Alekseeva Ekaterina A. , Tarasov Vadim V. , Zamyatnin Andrey A. , Nemtsova Marina V.
Published: April 2022

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of IL6, IL6R, TNFRSF1A, CTLA4, IL10, IL23R, and PADI4; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes (IL1B, IL17A, PADI4, DHODH, GLCCI1, IL23R, and TNFAIP3), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel.
Interprofessional Collaboration and Diabetes Management in Primary Care: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes
Authors: Nurchis Mario Cesare , Sessa Giorgio , Pascucci Domenico , Sassano Michele , Lombi Linda , Damiani Gianfranco
Published: April 2022

The global spread of diabetes poses serious threats to public health requiring a patient-centered approach based both on interprofessional collaboration (IPC) given by the cooperation of several different health professionals, and patients’ perspective through the assessment of Patient-Reported Outcomes (PROs). The aim of the present study is to evaluate the impact of interprofessional collaboration interventions, for the management of type 2 diabetes in primary care settings, through PROs. A systematic review and meta-analysis was conducted querying the PubMed, Scopus and Embase databases. Out of the 1961 papers initially retrieved, 19 met the inclusion criteria. Interprofessional collaboration is significantly associated with an increase in both patient’s satisfaction (SMD 0.32 95% CI 0.05–0.59) and in the mental well-being component of the HRQoL (SMD 0.18; 95% CI 0.06–0.30), and there was also promising evidence supporting the association between an interprofessional approach and an increase in self-care and in generic and specific quality-of-life. No statistical differences were found, supporting the positive impact on IPC interventions on the physical component of the HRQoL, depression, emotional distress, and self-efficacy. In conclusion, the effect of IPC impacts positively on the few areas assessed by PROMs. Policymakers should promote the widespread adoption of a collaborative approach as well as to endorse an active engagement of patients across the whole process of care.
Improving E-Commerce Distribution through Last-Mile Logistics with Multiple Possibilities of Deliveries Based on Time and Location
Authors: Escudero-Santana Alejandro , Muñuzuri Jesús , Lorenzo-Espejo Antonio , Muñoz-Díaz María-Luisa
Published: April 2022

The rapid rise of electronic commerce has entailed an increase in logistic complexity, with last-mile logistics being the most critical element in deliveries. Since users prefer goods to be delivered at home, one of the biggest challenges faced by e-commerce is to reduce the number of incidents that occur in the delivery of goods to the homes of customers. In many cases, these deliveries cannot take place because recipients are not at the agreed delivery point, leading to a decrease in the quality of service and an increase in distribution costs. Furthermore, sometimes the delivery policies are not in tune with the customers’ expectations. This work presents a new perspective of the last-mile logistics in the context of multichannel retail, asking customers to provide several delivery locations (at home, at work, at a familiar home, in a shop, in a locker, etc.) associated with different time windows. In addition, the customer could state their preferences about these locations. This work formulates the problem and develops different approaches to solve it. A benchmark is proposed to analyze the performance and limitations. The results reveal that a distribution policy with several locations can improve the efficiency of electronic commerce by reducing delivery costs. The findings of this study have several implications for distribution companies.
Does De-Iconization Affect Visual Recognition of Russian and English Iconic Words?
Authors: Lavitskaya Yulia , Sedelkina Yulia , Korotaevskaya Elizaveta , Tkacheva Liubov , Flaksman Maria , Nasledov Andrey
Published: April 2022

Iconic words constitute an integral part of the lexicon of a language, exhibiting form-meaning resemblance. Over the course of time, semantic and phonetic transformations “weaken” the degree of iconicity of a word. This iconicity loss is known as the process of de-iconization, which is divided into four stages, and, at each consecutive stage, the degree of a word’s iconicity is reduced. The current experimental study is the first to compare and contrast how English (N = 50) and Russian (N = 106) subjects recognize visually presented native iconic words (N = 32). Our aim is two-fold: first, to identify native speakers’ ability to perceive the fine-grained division of iconicity; and second, to control for the influence of participants’ native languages. This enables us to provide a more exhaustive analysis of the role of iconicity in word recognition and to combine empirical results with a theoretical perspective. The findings showed that the speakers of these languages are not equally sensitive to iconicity. As opposed to the English-speaking participants, who showed almost similar performance on each group of iconic words, the Russian participants tended to respond slower and less accurately to the words that were higher in iconicity. We discuss the major factors that may affect iconic word recognition in each language.