bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preclinical Study on Brugada Syndrome with a CACNB2 Variant Using Human Cardiomyocytes from Induced Pluripotent Stem Cells
Authors: Zhong Rujia , Schimanski Theresa , Zhang Feng , Lan Huan , Hohn Alyssa , Xu Qiang , Huang Mengying , Liao Zhenxing , Qiao Lin , Yang Zhen , Li Yingrui , Zhao Zhihan , Li Xin , Rose Lena , Albers Sebastian , Maywald Lasse , Müller Jonas , Dinkel Hendrik , Saguner Ardan , Janssen Johannes W. G. , Swamy Narasimha , Xi Yannick , Lang Siegfried , Kleinsorge Mandy , Duru Firat , Zhou Xiaobo , Diecke Sebastian , Cyganek Lukas , Akin Ibrahim , El-Battrawy Ibrahim
Published: July 2022

Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associated with Brugada syndrome (BrS). However, the investigation of the human cellular phenotype and the use of drugs for BrS in presence of variant in the calcium channel subunit is still lacking. Objectives: The objective of this study was to establish a cellular model of BrS in the presence of a CACNB2 variant of uncertain significance (c.425C > T/p.S142F) using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and test drug effects using this model. Methods and results: This study recruited cells from a patient with Brugada syndrome (BrS) and recurrent ventricular fibrillation carrying a missense variant in CACNB2 as well as from three healthy independent persons. These cells (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used for this study. The hiPSC-CMs from the BrS patient showed a significantly reduced L-type calcium channel current (ICa-L) compared with the healthy control hiPSC-CMs. The inactivation curve was shifted to a more positive potential and the recovery from inactivation was accelerated. The protein expression of CACNB2 of the hiPSC-CMs from the BrS-patient was significantly decreased compared with healthy hiPSC-CMs. Moreover, the correction of the CACNB2 site-variant rescued the changes seen in the hiPSC-CMs of the BrS patient to the normal state. These data indicate that the CACNB2 gene variant led to loss-of-function of L-type calcium channels in hiPSC-CMs from the BrS patient. Strikingly, arrhythmia events were more frequently detected in BrS-hiPSC-CMs. Bisoprolol (beta-blockers) at low concentration and quinidine decreased arrhythmic events. Conclusions: The CACNB2 variant (c.425C > T/p.S142F) causes a loss-of-function of L-type calcium channels and is pathogenic for this type of BrS. Bisoprolol and quinidine may be effective for treating BrS with this variant.
High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation
Authors: Yao Xiuting , Yang Chenxi , Wang Conghui , Li Hong , Zhao Jingyi , Kang Xiaomin , Liu Zhuodong , Chen Lingyan , Chen Xinyu , Pu Tianshu , Li Qinyang , Liu Lijie
Published: July 2022

Adolescence is a developmental epoch characterized by massive neural circuit remodeling; thus, the brain is particularly vulnerable to environmental influences during this period. Excessive high-fat diet (HFD) consumption, which is very common among adolescents, has long been recognized as a potent risk factor for multiple mood disorders, including depression and anxiety. However, the precise mechanisms underlying the influences of HFD consumption in adolescence on emotional health are far from clear. In the present study, C57BL/6 mice were fed a control diet (CD) or HFD for about 4 weeks from postnatal day (P) 28 to P60, spanning most of the adolescence period, and then subjected to behavioral assessments and histological examinations. HFD mice exhibited elevated levels of depression and anxiety, decreased hippocampal neurogenesis, and excessive microglial activation in the ventral hippocampus. Furthermore, in HFD-fed mice, microglia showed increased DCX+ inclusions, suggesting aberrant microglial engulfment of newborn neurons in HFD-fed adolescents. To our knowledge, this is the first observation suggesting that the negative effects of HFD consumption in adolescence on emotion and neuroplasticity may be attributed at least in part to aberrant microglial engulfment of nascent neurons, extending our understanding of the mechanism underlying HFD-related affective disorders in young people.
Quantum Randomness in Cryptography—A Survey of Cryptosystems, RNG-Based Ciphers, and QRNGs
Authors: Saini Anish , Tsokanos Athanasios , Kirner Raimund
Published: July 2022

Cryptography is the study and practice of secure communication with digital data and focuses on confidentiality, integrity, and authentication. Random number generators (RNGs) generate random numbers to enhance security. Even though the cryptographic algorithms are public and their strength depends on the keys, cryptoanalysis of encrypted ciphers can significantly contribute to the unveiling of the cipher’s key. Therefore, to ensure high data security over a network, researchers need to improve the randomness of keys as they develop cryptosystems. Quantum particles have a leading edge in advancing RNG technology as they can provide true randomness, unlike pseudo-random numbers generators (PRNGs). In order to increase the level of the security of cryptographic systems based on random numbers, this survey focuses on three objectives: Cryptosystems with related cryptographic attacks, RNG-based cryptosystems, and the design of quantum random number generators (QRNGs). This survey aims to provide researchers with information about the importance of RNG-based ciphers and various research techniques for QRNGs that can incorporate quantum-based true randomness in cryptosystems.
About Challenges in Data Analytics and Machine Learning for Social Good
Authors: Martoglia Riccardo , Montangero Manuela
Published: July 2022

The large number of new services and applications and, in general, all our everyday activities resolve in data mass production: all these data can become a golden source of information that might be used to improve our lives, wellness and working days. (Interpretable) Machine Learning approaches, the use of which is increasingly ubiquitous in various settings, are definitely one of the most effective tools for retrieving and obtaining essential information from data. However, many challenges arise in order to effectively exploit them. In this paper, we analyze key scenarios in which large amounts of data and machine learning techniques can be used for social good: social network analytics for enhancing cultural heritage dissemination; game analytics to foster Computational Thinking in education; medical analytics to improve the quality of life of the elderly and reduce health care expenses; exploration of work datafication potential in improving the management of human resources (HRM). For the first two of the previously mentioned scenarios, we present new results related to previously published research, framing these results in a more general discussion over challenges arising when adopting machine learning techniques for social good.
Mosquitocidal Activity of the Methanolic Extract of Annickia chlorantha and Its Isolated Compounds against Culex pipiens, and Their Impact on the Non-Target Organism Zebrafish, Danio rerio
Authors: Selim Tharwat , Abd-El Rahman Ibrahim , Mahran Hesham , Adam Hamza , Imieje Vincent , Zaki Ahmed , Bashar Mansour , Hwihy Hossam , Hamed Abdelaaty , Elhenawy Ahmed , Abou-Amra Eman , El-Didamony Samia , Hasaballah Ahmed
Published: July 2022

In this study, the crude extract and its isolated compounds from the stem bark of Annickia chlorantha were tested for their larvicidal, developmental, and repellent activity against the mosquito vector, Culex pipiens, besides their toxicity to the non-target aquatic organism, the zebrafish (Danio rerio). The acute larvicidal activity of isolated compounds; namely, palmatine, jatrorrhizine, columbamine, β-sitosterol, and Annickia chlorantha methanolic extract (AC), was observed. Developmentally, the larval duration was significantly prolonged when palmatine and β-sitosterol were applied, whereas the pupal duration was significantly prolonged for almost all treatments except palmatine and jatrorrhizine, where it shortened from those in the control. Acetylcholinesterase (AChE) enzyme showed different activity patterns, where it significantly increased in columbamine and β-sitosterol, and decreased in (AC), palmatine, and jatrorrhizine treatments, whereas glutathione S-transferase (GST) enzyme was significantly increased when AC methanolic extract/isolated compounds were applied, compared to the control. The adult emergence percentages were significantly decreased in all treatments, whereas tested compounds revealed non-significant (p > 0.05) changes in the sex ratio percentages, with a slight female-to-male preference presented in the AC-treated group. Additionally, the tested materials revealed repellence action; interestingly, palmatine and jatrorrhizine recorded higher levels of protection, followed by AC, columbamine, and β-sitosterol for 7 consecutive hours compared to the negative and positive control groups. The non-target assay confirms that the tested materials have very low toxic activity compared to the reported toxicity against mosquito larvae. A docking simulation was employed to better understand the interaction of the isolated compounds with the enzymes, AChE and GST. Additionally, DFT calculations revealed that the reported larvicidal activity may be due to the differing electron distributions among tested compounds. Overall, this study highlights the potential of A. chlorantha extract and its isolated compounds as effective mosquitocidal agents with a very low toxic effect on non-target organisms.
A Non-Destructive High-Speed Procedure to Obtain DNA Barcodes from Soft-Bodied Insect Samples with a Focus on the Dipteran Section of Schizophora
Authors: Stein Frederik , Wagner Stefan , Bräsicke Nadine , Gailing Oliver , Moura Carina C. M. , Götz Monika
Published: July 2022

While the need for biodiversity research is growing, paradoxically, global taxonomical expertise is decreasing as a result of the neglected funding for young academics in taxonomy. Non-destructive approaches for DNA barcoding are necessary for a more efficient use of this dwindling expertise to fill gaps, and identify incorrect entries in sequence databases like BOLD or GenBank. They are efficient because morphological re-examination of species vouchers is still possible post-DNA barcoding. Non-destructive approaches for Diptera with a comprehensive species representation or the consideration of diagnostic fragile morphological characters are missing. Additionally, most non-destructive approaches combine a time intensive and non-destructive digestion step with common DNA extraction methods, such as commercial kits or CTAB DNA isolation. We circumvented those approaches and combined a modified non-destructive TE buffer high-speed DNA extraction, with a PCR inhibitor-resistant PCR reaction system, to a non-destructive DNA barcoding procedure for fresh and frozen samples of the Schizophora (Diptera). This method avoids morphological impairment and the application of harmful chemicals, is cost and time effective, restricts the need for laboratory equipment to a minimum, and prevents cross-contamination risk during DNA isolation. Moreover, the study indicates that the presented non-destructive DNA barcoding procedure is transferable to other soft-bodied insects. We suggest that PCR inhibitor-resistant master mixes enable the development of new—and the modification of existing—non-destructive approaches with the avoidance of further DNA template cleaning.
Current Trends in Bone Augmentation Techniques and Dental Implantology: An Editorial Overview
Authors: Angelis Nicola De , Benedicenti Stefano , Zekiy Angelina , Amaroli Andrea
Published: July 2022

Dental implants and related bone augmentation problems have seen major progress since early protocols were tested in the 1980s [...]
DNase-1 Treatment Exerts Protective Effects in Neurogenic Pulmonary Edema via Regulating the Neutrophil Extracellular Traps after Subarachnoid Hemorrhage in Mice
Authors: Wu Xinyan , Guo Yinghan , Zeng Hanhai , Chen Gao
Published: July 2022

It has been reported that neutrophil extracellular traps (NETs) involve inflammation, coagulation and cell death. Acute lung injury is also considered to be connected with NETs. Deoxyribonuclease I (DNase-1), a clinical medication for the respiratory system, has been reported to degrade cell-free DNA (cfDNA), which is the main component of NETs. Herein, we did research to clarify the therapeutic value of DNase-1 in NPE after SAH. In this model, we found that the treatment of DNase-1 remarkably decreased lung water, neutrophilic infiltration and inflammation. In addition, DNase-1 inhibited the NETs and proinflammatory subtype transition of the macrophages. Moreover, the depletion of neutrophil also verified the role of NETs in NPE. Our results suggest that DNase-1 has the potential to effectively relieve the NPE after SAH and to be a clinical drug for use after SAH.
The Impact of Air Pollution on Frequent Exacerbations among COPD Patients: An Observational Study on the Population of Western Romania
Authors: Bălă Gabriel-Petrică , Timar Bogdan , Gorun Florin , Motisan Radu , Pescaru Camelia , Tudorache Emanuela , Marc Monica , Manolescu Diana , Citu Cosmin , Oancea Cristian
Published: July 2022

Patients with respiratory pathologies are the risk group most affected by air pollution, being directly exposed, especially those diagnosed with chronic obstructive pulmonary disease (COPD). In this observational study, which included 79 patients, we evaluated whether COPD patients with the frequent exacerbating phenotype or the infrequent exacerbating phenotype live in residences with higher values of air pollution. An air quality monitoring station was installed in each patient’s house for at least 24 h and PM 1.0, PM 2.5, and PM 10 were measured. Average PM 1.0, PM 2.5, and PM 10 values were lower in the group of infrequently exacerbating patients compared to the frequently exacerbating ones. For every 1 µg/m3 increase in the average values of PM 1.0, PM 2.5, and PM 10, there is an increase of 1.7%, 1.8% and 1%, respectively, in the risk of developing exacerbations. More importantly, an average value of PM 1.0, PM 2.5, and PM 10 above 32.21 µg/m3, 82.32 µg/m3 and 42.89 µg/m3 increases the probability of developing an exacerbation by 3.83, 10.14, and 4.12 times, respectively. Our analysis showed that COPD patients with a frequently exacerbating phenotype live in residences with high levels of air pollution compared to infrequently exacerbating ones.
Assessment of Renal Transplant Perfusion by Contrast-Enhanced Ultrasound after Switch from Calcineurin Inhibitor to Belatacept: A Pilot Study
Authors: Osmanodja Bilgin , Muench Frédéric , Holderied Alexander , Budde Klemens , Fischer Thomas , Lerchbaumer Markus Herbert
Published: July 2022

Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival but are nephrotoxic and vasoconstrictive. Vasoconstriction is potentially reversible after switching from CNIs to belatacept. The kidney allograft shows optimal requirements for dynamic perfusion imaging using contrast-enhanced ultrasound (CEUS). We performed standardized CEUS in patients after switching from CNIs to belatacept for clinical indication to study the suitability of CEUS, in order to assess the effects of CNI cessation on kidney allograft perfusion. Eleven kidney transplant patients were enrolled from February 2020 until November 2020. Demographic, clinical, and laboratory parameters, as well as perfusion imaging, were assessed at baseline and 6 months after switching immunosuppression. Quantification of perfusion imaging on CEUS was performed using a post-processing software tool on uncompressed DICOM cine loops. After CNI cessation, estimated glomerular filtration rate increased by 4.8 mL/min/1.73 m2 (16%). Despite good quality of fit and comparable regions of interest in baseline and follow-up CEUS examinations, quantification of perfusion imaging showed a slightly improved cortical perfusion without reaching statistical significance after CNI cessation. This is the first study that systematically investigates the suitability of CEUS to detect changes of microvascular perfusion in kidney transplant recipients in vivo. No significant differences could be detected in perfusion measurements before and after CNI cessation.
Lipid Profile, Lp(a) Levels, and HDL Quality in Adolescents with Down Syndrome
Authors: Krzesińska Aleksandra , Kłosowska Anna , Sałaga-Zaleska Kornelia , Ćwiklińska Agnieszka , Mickiewicz Agnieszka , Chyła Gabriela , Wierzba Jolanta , Jankowski Maciej , Kuchta Agnieszka
Published: July 2022

The improvement in the lifespan of individuals with Down syndrome (DS) has created interest in the context of the development of age-related diseases. Among them is atherosclerosis-based cardiovascular disease (CVD), which seems to be an especially urgent and important issue. The aim of the present study was to evaluate the lipid markers that may clarify cardiovascular risk profiles in individuals with DS. To this end, we analyzed lipid profile parameters, including lipoprotein(a) (Lp(a)) levels, protein composition, and the antioxidative properties of high-density lipoprotein (HDL), in 47 adolescents with DS and 47 individuals without DS. Compared with the control group (C), subjects with DS had significantly increased concentrations of low-density lipoprotein cholesterol (105 ± 31 vs. 90 ± 24 mg/dL, p = 0.014), non-high-density lipoprotein cholesterol (120 ± 32 vs. 103 ± 26 mg/dL, p = 0.006), and triglycerides (72 [55–97] vs. 60 [50–77] mg/dL, p = 0.048). We found that patients with DS were characterized by significantly higher Lp(a) levels (31.9 [21.5–54.3] vs. 5.2 (2.4–16.1) mg/dL, p < 0.001). In fact, 57% of individuals with DS had Lp(a) levels above 30 mg/dL, which was approximately four times higher than those in the control group (DS 57% vs. C 15%). Apart from decreased high-density lipoprotein cholesterol levels in the subjects with DS (53 ± 11 vs. 63 ± 12 mg/dL, p < 0.001), differences in parameters showing the quality of HDL particles were observed. The concentrations of the main proteins characterizing the HDL fraction, apolipoprotein A-I and apolipoprotein A-II, were significantly lower in the DS group (144 ± 21 vs. 181 ± 33 mg/dL, p < 0.001; 33 ± 6 vs. 39 ± 6 mg/dL, p < 0.001, respectively). No significant differences between the groups were observed for the concentration of paraoxonase-1 (DS 779 ± 171 vs. C 657 ± 340 ng/mL, p = 0.063), enzyme activities toward paraoxon (DS 219 [129–286] vs. C 168 [114–272] IU/L, p = 0.949), or phenyl acetate (DS 101 ± 20 vs. C 93 ± 21 kIU/L, p = 0.068). There were no differences in myeloperoxidase activity between the study groups (DS 327 [300–534] vs. C 426 [358–533] ng/mL, p = 0.272). Our results are the first to demonstrate an unfavorable lipid profile combined with higher Lp(a) levels and quality changes in HDL particles in individuals with DS. This sheds new light on cardiovascular risk and traditional healthcare planning for adolescents with DS.
Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases
Authors: Püschel Gerhard Paul , Klauder Julia , Henkel Janin
Published: July 2022

Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.
Reducing the Burden of Migraine: Safety and Efficacy of CGRP Pathway-Targeted Preventive Treatments
Authors: Nissan George R. , Kim Richard , Cohen Joshua M. , Seminerio Michael J. , Krasenbaum Lynda J. , Carr Karen , Martin Vincent
Published: July 2022

Migraine is a highly disabling and often chronic neurological disease that affects more than one billion people globally. Preventive migraine treatment is recommended for individuals who have frequent and/or disabling attacks; however, many of the medications used for migraine prevention (e.g., antiepileptics, antidepressants, antihypertensives) were not specifically developed for migraine, and often have limited efficacy or poor tolerability. Four monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, which is believed to play a crucial role in the pathophysiology of migraine, have been approved by the US Food and Drug Administration for the preventive treatment of migraine in adults. All four migraine-specific treatments have demonstrated efficacy based on reductions in monthly days with migraine for patients with both episodic and chronic migraine, including those with comorbidities. They have also demonstrated favorable safety and tolerability profiles. Based on these accounts, CGRP pathway-targeted monoclonal antibodies have the potential to revolutionize preventive treatment for patients with migraine.
Impact of Service-Learning on Physiotherapy Students: Exercise Programs for Patients with Heart Transplantation and Acute Coronary Syndrome—A Randomized Clinical Trial
Authors: Marques-Sule Elena , Chiva-Bartoll Oscar , Carrasco Juan J. , Hernández-Guillén David , Pérez-Alenda Sofía , Francisco-Garcés Xavier , Sentandreu-Mañó Trinidad , Blesa Jesús
Published: July 2022

Introduction. Service-learning (SL) seems to be useful for healthcare students. This study aimed at comparing an SL program versus a traditional approach (TA) on moral sensitivity, ethical competences, knowledge, teaching quality, SL participation and performance, and satisfaction in physiotherapy students. Methods. Randomized clinical trial. A total of 32 physiotherapy students were allocated to an SL group (SLG, n = 16), or to a TA group (TAG, n = 16). Participants had to create an exercise program for patients with heart transplantation and acute coronary syndrome. The SLG performed the program with real patients, whilst the TAG performed a traditional collaborative approach. Moral sensitivity, ethical competences, knowledge and teaching quality were assessed pre- and post-intervention. SL participation and performance and satisfaction of the SLG were assessed post-intervention. Results. After the intervention, the SLG showed higher moral sensitivity, ethical competences, knowledge and reported better teaching quality than the TAG. The SL program was useful, addressed a real need, contributed to learning, helped to solve problems, facilitated better comprehension, increased motivation, and students would like to use SL in other subjects. Conclusions. The SL program had a positive impact on students, encouraging the implementation of similar SL interventions. SL may be considered a teaching–learning methodology of choice in physiotherapy students.
Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients
Authors: Mekontso Dessap Armand , Hanrott Kate , Powley William M. , Fowler Andrew , Bayliffe Andrew , Bagate François , Hall David A. , Lazaar Aili L. , Budd David C. , Vieillard-Baron Antoine
Published: July 2022

Background: Right ventricular (RV) dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (ACE2), a key enzyme of the renin-angiotensin system (RAS), using recombinant human ACE2 (rhACE2) could alleviate RAS-mediated vasoconstriction and vascular remodeling. Methods: This prospective observational study investigated the association between concentrations of RAS peptides (Ang II or Ang(1–7)) and markers of RV function, as assessed by echocardiography (ratio of RV to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure (PASP)). Results: Fifty-seven mechanically ventilated patients were enrolled. Incidence rates of acute cor pulmonale (ACP) and pulmonary circulatory dysfunction (PCD) were consistent with previous studies. In the 45 evaluable participants, no notable or consistent changes in RAS peptides concentration were observed over the observation period, and there was no correlation between Ang II concentration and either PASP or RV size. The model of the predicted posterior distributions for the pre- and post-dose values of Ang II demonstrated no change in the likelihood of PCD after hypothetical dosing with rhACE2, thus meeting the futility criteria. Similar results were observed with the other RAS peptides evaluated. Conclusions: Pre-defined success criteria for an association between PCD and the plasma RAS peptides were not met in the mechanically ventilated unselected patients.
Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children
Authors: Buonsenso Danilo , Valentini Piero , De Rose Cristina , Tredicine Maria , Pereyra Boza Maria del Carmen , Camponeschi Chiara , Morello Rosa , Zampino Giuseppe , Brooks Anna E. S. , Rende Mario , Ria Francesco , Sanguinetti Maurizio , Delogu Giovanni , Sali Michela , Di Sante Gabriele ,   on behalf of the Gemelli-Pediatric COVID-19 Team
Published: July 2022

Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.
Clostridioides difficile Infection in Patients after Organ Transplantation—A Narrative Overview
Authors: Dudzicz-Gojowy Sylwia , Więcek Andrzej , Adamczak Marcin
Published: July 2022

Clostridioides difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea. The pathogenesis of this infection participates in the unstable colonization of the intestines with the physiological microbiota. Solid-organ-transplant (SOT) patients and patients after hematopoietic stem cell transplantation are more prone to CDI compared to the general population. The main CDI risk factors in these patients are immunosuppressive therapy and frequent antibiotic use leading to dysbiosis. The current review article provides information about the risk factors, incidence and course of CDI in patients after liver, kidney, heart and lung transplantation and hematopoietic stem cell transplantation.
Potential of Multiplex Polymerase Chain Reaction Performed on Protected Telescope Catheter Samples for Early Adaptation of Antimicrobial Therapy in ARDS Patients
Authors: Razazi Keyvan , Delamaire Flora , Fihman Vincent , Boujelben Mohamed Ahmed , Mongardon Nicolas , Gendreau Ségolène , de Roux Quentin , de Prost Nicolas , Carteaux Guillaume , Woerther Paul-Louis , Mekontso Dessap Armand
Published: July 2022

Background: Diagnosis of co/superinfection in patients with Acute Respiratory Distress Syndrome (ARDS) is challenging. The FilmArray Pneumonia plus Panel (bioMérieux, France), a new rapid multiplex Polymerase Chain Reaction (mPCR), has never been assessed on a blinded protected telescope catheter (PTC) samples, a very common diagnostic tool in patients under mechanical ventilation. We evaluated the performance of mPCR on PTC samples compared with conventional culture and its impact on antibiotic stewardship. Methods: Observational study in two intensive care units, conducted between March and July 2020, during the first wave of the COVID-19 pandemic in France. Results: We performed 125 mPCR on blinded PTC samples of 95 ARDS patients, including 73 (77%) SARS-CoV-2 cases and 28 (29%) requiring extracorporeal membrane oxygenation. Respiratory samples were drawn from mechanically ventilated patients either just after intubation (n = 48; 38%) or later for suspected ventilator-associated pneumonia (VAP) (n = 77; 62%). The sensitivity, specificity, positive, and negative predictive values of mPCR were 93% (95% CI 84–100), 99% (95% CI 99–100), 68% (95% CI 54–83), and 100% (95% CI 100–100), respectively. The overall coefficient of agreement between mPCR and standard culture was 0.80 (95% CI 0.68–0.89). Intensivists changed empirical antimicrobial therapy in only 14% (18/125) of cases. No new antibiotic was initiated in more than half of the CAP/HAP pneumonia-suspected cases (n = 29; 60%) and in more than one-third of those suspected to have VAP without affecting or delaying their antimicrobial therapy. Conclusions: Rapid mPCR was feasible on blinded PTC with good sensitivity and specificity. New antibiotics were not initiated in more than half of patients and more than one-third of VAP-suspected cases. Further studies are needed to assess mPCR potential in improving antibiotic stewardship.
Imaging Activated-T-Lymphocytes in the Salivary Glands of Patients with Sjögren’s Syndrome by 99mTc-Interleukin-2: Diagnostic and Therapeutic Implications
Authors: Campagna Giuseppe , Anzola Luz Kelly , Varani Michela , Lauri Chiara , Gentiloni Silveri Guido , Chiurchioni Lorenzo , Spinelli Francesca Romana , Priori Roberta , Conti Fabrizio , Signore Alberto
Published: July 2022

Background: Sjögren’s syndrome (SS) is a progressive autoimmune disease characterized by local mononuclear cell infiltration of the salivary and lachrymal glands. Labial biopsy demonstrates local infiltration by Th1 cells that produce pro-inflammatory cytokines, such as interleukin-2 (IL2). The aim of this study was to assess the utility of 99mTc-labelled-IL2 (99mTc-IL2) in evaluating in vivo the extent and severity of lympho-mononuclear cell infiltration in the salivary glands of patients with SS. Methods: We investigated 48 patients with primary SS and 27 control subjects using 99mTc-IL2 scintigraphy. Furthermore, in a subgroup of 30 patients, we also performed 99mTc-pertechnetate scintigraphy (99mTcO4−) for evaluation of the salivary gland function. Results: 99mTc-IL2 uptake in the salivary glands of SS patients was higher than in the control subjects (1.30 ± 0.16 vs. 0.83 ± 0.08 for parotids and 1.36 ± 0.15 vs. 1.16 ± 0.07 for submandibular glands; p < 0.0001). The salivary gland uptake of 99mTc-IL2 in patients with a longer history of disease was lower compared with the recently diagnosed patients. A significant direct correlation was found between the uptake of 99mTc-IL2 and histology. Conclusions: 99mTc-IL2 scintigraphy showed that the degree of lymphocytic infiltration of major salivary glands is variable in patients with different disease durations. Patients with a high 99mTc-IL2 uptake could be efficiently treated with immuno-modulatory drugs and the efficacy of treatment could be followed-up by 99mTc-IL2 scintigraphy.
Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review
Authors: Welzel Tatjana , Oefelein Lea , Holzer Ursula , Müller Amelie , Menden Benita , Haack Tobias B. , Groβ Miriam , Kuemmerle-Deschner Jasmin B.
Published: July 2022

Background: Variants in the phospholipase C gamma 2 (PLCG2) gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. Linking the clinical phenotype with the genotype is relevant in making the final diagnosis. Methods: This is a single center case series of five related patients (4–44 years), with a history of autoinflammation and immune dysregulation. Clinical and laboratory characteristics were recorded and a literature review of APLAID/PLAID was performed. Results: All patients had recurrent fevers, conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold-induced urticaria and recurrent airway infections. Hearing loss was detected in two patients. Inflammatory parameters were slightly elevated during flares. Unswitched B-cells were decreased. Naïve IgD+CD27− B-cells and unswitched IgD+CD27+ B-cells were decreased; switched IgD-CD27+ B-cells were slightly increased. T-cell function was normal. Genetic testing revealed a heterozygous missense variant (c.77C>T, p.Thr26Met) in the PLCG2 gene in all patients. Genotype and phenotype characteristics were similar to previously published PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies) patients. Furthermore, they displayed characteristics for both PLAID and APLAID (recurrent infections, abdominal pain/diarrhea) with normal T-cell function. Conclusion: The heterozygous missense PLCG2 gene variant (c.77C>T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.
Assessment of Renal Allograft Stiffness and Viscosity Using 2D SWE PLUS and Vi PLUS Measures—A Pilot Study
Authors: Maralescu Felix-Mihai , Bende Felix , Sporea Ioan , Popescu Alina , Șirli Roxana , Schiller Adalbert , Petrica Ligia , Moga Tudor Voicu , Mare Ruxandra , Grosu Iulia , Bob Flaviu
Published: July 2022

Elastography is a useful noninvasive tool for the assessment of renal transplant recipients. 2D-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) have emerged as novel techniques that promise to offer improved renal stiffness and viscosity measures due to improved processing algorithms. Methods: We performed a cross-sectional study of 50 kidney transplanted patients (16 women, 34 men; mean age of 47.5 ± 12.5; mean estimated glomerular filtration rate (eGFR) estimated by Chronic Kidney Disease Epidemiology Collaboration formula: 52.19 ± 22.6 mL/min/1.73 m2; and a mean duration after transplant of 10.09 ± 5 years). For every patient, we obtained five valid measurements of renal stiffness (obtained from five different frames in the cortex of the renal graft), and also tissue viscosity, with a C6-1X convex transducer using the Ultra-Fast™ software available on the Aixplorer Mach 30 ultrasound system (Supersonic Imagine, Aix-en-Provence, France). The median values of elastographic and viscosity measures have been correlated with the patients’ demographic, biological, and clinical parameters. Results: We obtained a cut-off value of renal cortical stiffness of <27.3 kiloPascal(kPa) for detection of eGFR < 60 mL/min/1.73 m2 with 80% sensitivity and 85% specificity (AUC = 0.811, p < 0.0001), a cut-off value of <26.9 kPa for detection of eGFR < 45 mL/min/1.73 m2 with 82.6% sensitivity and 74% specificity (AUC = 0.789, p < 0.0001), and a cut-off value of <23 kPa for detection of eGFR < 30 mL/min/1.73 m2 with 88.8% sensitivity and 75.6% specificity (AUC = 0.852, p < 0.0001). We found a positive correlation coefficient between eGFR and the median measure of renal cortical stiffness (r = 0.5699, p < 0.0001), between eGFR the median measure of viscosity (r = 0.3335, p = 0.0180), between median depth of measures and renal cortical stiffness (r = −0.2795, p = 0.0493), and between median depth of measures and body mass index (BMI) (r = 0.6574, p < 0.0001). Our study showed good intra-operator agreement for both 2D SWE PLUS measures—with an intraclass correlation coefficient (ICC) of 0.9548 and a 95% CI of 0.9315 to 0.9719—and Vi PLUS, with an ICC of 0.8323 and a 95% CI of 0.7457 to 0.8959. The multivariate regression model showed that 2D SWE PLUS values were associated with eGFR, Vi PLUS, and depth of measures. Conclusions: Assessment of renal allograft stiffness and viscosity may prove to be an effective method for identifying patients with chronic allograft injury and could prove to be a low-cost approach to provide additional diagnostic information of kidney transplanted patients.
Metal Artifact Reduction Sequences MRI: A Useful Reference for Preoperative Diagnosis and Debridement Planning of Periprosthetic Joint Infection
Authors: Huang Changyu , Chen Yang , Ding Haiqi , Huang Zida , Zhang Chaofan , Li Wenbo , Liu Xi , Tu Zhanhai , Zhang Wenming , Fang Xinyu
Published: July 2022

The diagnosis and treatment of periprosthetic joint infection (PJI) is complex and the use of MRI in PJI is gaining attention from orthopedic surgeons as MR technology continues to advance. This study aimed to investigate whether metal artefact reduction sequence (MARS) MRI could be used as an adjunct in the preoperative diagnosis of PJI and to explore its role in PJI debridement planning. From January 2020 to November 2021, participants with metal joint prostheses that needed to be judged for infection were prospectively enrolled. According to Musculoskeletal Infection Society standards, 31 cases were classified as infection, and 20 as non-infection. The sensitivity and specificity of MARS MRI for the diagnosis of PJI were 80.65% and 75%, respectively. In MARS MRI, the incidence of bone destruction, lamellar synovitis, and extracapsular soft tissue oedema were significantly higher in PJI than in non-PJI. Fourteen suspicious occult lesions were found in the preoperative MARS MRI in 9 cases, and the location of 9 infection lesions was confirmed intraoperatively. In conclusion, MARS MRI is an effective diagnostic tool for PJIand can provide a visual reference for preoperative surgical planning.
Renal Toxicities in Cancer Patients Receiving Immune-Checkpoint Inhibitors: A Meta-Analysis
Authors: Righini Matteo , Mollica Veronica , Rizzo Alessandro , La Manna Gaetano , Massari Francesco
Published: July 2022

Aim: We performed a meta-analysis of the available clinical trials of immune-checkpoint inhibitors to assess risk differences and relative risks of renal toxicity. Methods: 17 randomized phase III studies were selected, including 10,252 patients. Results: The administration of immune-checkpoint inhibitors resulted in an overall low-grade, high-grade and all-grade renal toxicity Risk Difference of: 0.746% (95% CI 0.629% to 1.15%, p < 0.001—random), 0.61% (95% CI, 0.292–0.929%, p < 0.001—fixed) and 1.2% (95% CI, 0.601–1.85%—random), respectively. The pooled Relative Risk of low-grade, high-grade and all-grade renal toxicity was: 2.185 (95% CI 1.515–3.152—fixed), 2.610 (95% CI, 1.409–4.833, p = 0.002—fixed) and 2.473 (95% CI, 1.782–3.431, p < 0.001—fixed), respectively. An increased risk of renal toxicity was evident in some subgroups more than others. Conclusion: Immune-checkpoint inhibitors are associated with an increased risk of renal toxicity.
Anastomotic Leak Impact on Long-Term Survival after Right Colectomy for Cancer: A Propensity-Score-Matched Analysis
Authors: Dulskas Audrius , Kuliavas Justas , Sirvys Artiomas , Bausys Augustinas , Kryzauskas Marius , Bickaite Klaudija , Abeciunas Vilius , Kaminskas Tadas , Poskus Tomas , Strupas Kestutis
Published: July 2022

Our goal was to assess the impact of anastomotic leaks (ALs) on oncologic outcomes using a case-matched analysis. Patients undergoing right hemicolectomy for cancer between 2014 and 2018 were included. The main variables were the risk factor of anastomotic leak, overall survival and disease-free survival. Propensity score matching was performed according to the patient’s age, co-morbidities and TNM staging as well as the type of procedure. Oncologic outcomes were analyzed. We included 488 patients and performed final analysis on 69 patients. The AL rate was 4.71% (23 patients). Intrahospital mortality was significantly higher in the AL group, at 1.3% (6 of 465) vs. 8.7% (2 of 23), p = 0.05. Three-year overall survival (OS) in the non-AL group was higher, although the difference could not be considered significant (71.5% vs. 37.3%, p = 0.082); similarly, the likelihood for impaired 3-year progression-free survival (PFS) was lower, but the difference here could also not be considered significant (69.3% vs. 37.3%, p = 0.106). Age, advanced tumor stage, lymph node metastases and distant metastases were associated with higher probability of death or recurrence of disease. In contrast, minimally invasive surgery was associated with lower probability of death (HR (95% CI): 0.99 (0.14–0.72); p = 0.023) and recurrence of disease (HR (95% CI): 0.94 (0.13–0.68); p = 0.020). In an adjusted Cox regression analysis, AL, age and distant metastases were associated with poor long-term survival. Moreover, AL, age and distant metastases were associated with higher probability of recurrence of disease. Based on our results, AL is a significant factor for worse oncologic outcomes. Simple summary: we aimed to assess patients with anastomotic leaks following right hemicolectomy for cancer. These patients were matched to patients without leaks. Propensity score analysis demonstrated that anastomotic leak was a marker of worse oncologic outcomes.
Correction: Lee et al. Long-Term Outcome of Epiretinal Membrane Surgery in Patients with Internal Limiting Membrane Dehiscence. J. Clin. Med. 2020, 9, 2470
Authors: Lee Min-Woo , Jung Il , Song Yong-Yeon , Baek Seung-Kook , Lee Young-Hoon
Published: July 2022

The authors would like to correct the keyword ‘bare RNLF’ to ‘RNFL schisis’ in their prior publication [...]
The Black Sea Zooplankton Mortality, Decomposition, and Sedimentation Measurements Using Vital Dye and Short-Term Sediment Traps
Authors: Litvinyuk Daria , Mukhanov Vladimir , Evstigneev Vladislav
Published: July 2022

The principal objectives of this research are to measure the non-consumptive mortality rate of marine copepod zooplankton and the sedimentation rate of copepod carcasses, using short-term sediment traps, and to reveal a correlation between the rates of the two competitive processes—sedimentation and degradation of the carcasses under turbulent mixing conditions. The traps were moored in Sevastopol Bay and adjacent coastal waters (the Black Sea) during summer and autumn seasons. A simulation model was developed to describe a wide range of processes in the trap and the water column above it and to interpret the results obtained with the sediment traps. Significant changes in the abundance of copepod carcasses (from 280 to 12,443 ind. m−3) and their fraction in the total zooplankton abundance (53 to 81%) were observed in the waters over short time periods, indicating a high variability of zooplankton mortality, sedimentation, and decomposition rates. Despite the high concentrations of copepod carcasses in the water column, the rates of their accumulation in the traps proved to be extremely low, which could be due to intense turbulent mixing of the waters. The carcass sedimentation rate and the flow of swimmers (motile copepods) into the traps were significantly higher in waters subjected to weaker turbulent mixing. The obtained estimates of the sedimentation rate of copepod carcasses (0.012 to 0.39 d−1) were comparable in value with the rate of their microbial decomposition (0.13 and 0.05 d−1 in the bay and adjacent waters, respectively). This confirmed the hypothesis on microbial decomposition as one of the key controls of the fraction of live zooplankton organisms in zooplankton.
Predictive Control for a Wave-Energy Converter Array Based on an Interconnected Model
Authors: Zhang Bo , Zhang Haixu , Yang Sheng , Chen Shiyu , Bai Xiaoshan , Khan Awais
Published: July 2022

This paper proposes a model predictive control (MPC) method based on an interconnected model to maximize the ocean wave energy extracted by a wave-energy converter (WEC) array. In the proposed method, a formally uniform interconnected model is applied to represent the dynamics of an array consisting of an arbitrary quantity of WECs, simultaneously considering the hydrodynamic interaction among all the WEC devices. First, the WEC devices and their hydrodynamic interaction are represented in an interconnected model that describes the networked dynamics of a variety of WEC arrays with distinct spatial geometry layout of the WEC devices deployed in the sea field. Second, based on the presented model, an MPC method is applied to achieve the coordinated control of the WEC array to improve its energy conversion efficiency under the constraints of buoy position and control force. Third, a hardware-in-the-loop (HIL) platform is developed to simulate the WEC array’s physical operating conditions, and the proposed method is implemented on the platform to test its performance. The test results show that the proposed MPC method using the interconnected model has a higher energy harvesting efficiency than the classic MPC method.