bluuebunny/crossref_metadata_2025 huggingface dataset:
Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain
Authors: Hwang Jisun , Jang Bohee , Kim Ayoung , Lee Yejin , Lee Joonha , Kim Chungho , Kim Jinmahn , Moon Kyeong Min , Kim Kyuhyung , Wagle Ram , Song Young-Han , Oh Eok-Soo
Published: July 2021

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.
Connexin43 in Germ Cells Seems to Be Dispensable for Murine Spermatogenesis
Authors: Rode Kristina , Langeheine Marion , Seeger Bettina , Brehm Ralph
Published: July 2021

Testicular Connexin43 (Cx43) connects adjacent Sertoli cells (SC) and SC to germ cells (GC) in the seminiferous epithelium and plays a crucial role in spermatogenesis. However, the distinction whether this results from impaired inter-SC communication or between GC and SC is not possible, so far. Thus, the question arises, whether a GC-specific Cx43 KO has similar effects on spermatogenesis as it is general or SC-specific KO. Using the Cre/loxP recombinase system, two conditional KO mouse lines lacking Cx43 in premeiotic (pGCCx43KO) or meiotic GC (mGCCx43KO) were generated. It was demonstrated by qRT-PCR that Cx43 mRNA was significantly decreased in adult pGCCx43KO mice, while it was also reduced in mGCCx43KO mice, yet not statistically significant. Body and testis weights, testicular histology, tubular diameter, numbers of intratubular cells and Cx43 protein synthesis and localization did not show any significant differences in semi-quantitative Western blot analysis and immunohistochemistry comparing adult male KO and WT mice of both mouse lines. Male KO mice were fertile. These results indicate that Cx43 in spermatogonia/spermatids does not seem to be essential for successful termination of spermatogenesis and fertility as it is known for Cx43 in somatic SC, but SC-GC communication might rather occur via heterotypic GJ channels.
Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD
Authors: Derdelinckx Judith , Reynders Tatjana , Wens Inez , Cools Nathalie , Willekens Barbara
Published: July 2021

Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clinical trials or have been used as rescue treatment in treatment-refractory cases. The development of antigen-specific cell-based immunotherapies for autoimmune diseases is slowed down by the rarity of the diseases, the lack of surrogate outcomes and biomarkers that are able to predict long-term outcomes and/or therapy effectiveness as well as challenges in the manufacturing of cellular products. These challenges are likely to be overcome by future research.
Antimicrobial Peptides with Antibacterial Activity against Vancomycin-Resistant Staphylococcus aureus Strains: Classification, Structures, and Mechanisms of Action
Authors: Hernández-Aristizábal Isabella , Ocampo-Ibáñez Iván Darío
Published: July 2021

The emergence of bacteria resistant to conventional antibiotics is of great concern in modern medicine because it renders ineffectiveness of the current empirical antibiotic therapies. Infections caused by vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) strains represent a serious threat to global health due to their considerable morbidity and mortality rates. Therefore, there is an urgent need of research and development of new antimicrobial alternatives against these bacteria. In this context, the use of antimicrobial peptides (AMPs) is considered a promising alternative therapeutic strategy to control resistant strains. Therefore, a wide number of natural, artificial, and synthetic AMPs have been evaluated against VRSA and VISA strains, with great potential for clinical application. In this regard, we aimed to present a comprehensive and systematic review of research findings on AMPs that have shown antibacterial activity against vancomycin-resistant and vancomycin-intermediate resistant strains and clinical isolates of S. aureus, discussing their classification and origin, physicochemical and structural characteristics, and possible action mechanisms. This is the first review that includes all peptides that have shown antibacterial activity against VRSA and VISA strains exclusively.
Simulations of Promising Indolizidine—α6-β2 Nicotinic Acetylcholine Receptor Complexes
Authors: Acquah Francis A. , Paramel Matthew , Kuta Adama , Hussaini Syed R. , Wallace David R. , Mooers Blaine H. M.
Published: July 2021

Smoking-cessation drugs bind many off-target nicotinic acetylcholine receptors (nAChRs) and cause severe side effects if they are based on nicotine. New drugs that bind only those receptors, such as α6β2* nAChR, implicated in nicotine addiction would avoid the off-target binding. Indolizidine (-)-237D (IND (-)-237D), a bicyclic alkaloid, has been shown to block α6β2* containing nAChRs and functionally inhibit the nicotine-evoked dopamine release. To improve the affinity of indolizidine (-)-237D for α6β2*, we built a library of 2226 analogs. We screened virtually the library against a homology model of α6β2 nAChR that we derived from the recent crystal structure of α4β2 nAChR. We also screened the crystal structure of α4β2 nAChR as a control on specificity. We ranked the compounds based on their predicted free energy of binding. We selected the top eight compounds bound in their best pose and subjected the complexes to 100 ns molecular dynamics simulations to assess the stability of the complexes. All eight analogs formed stable complexes for the duration of the simulations. The results from this work highlight nine distinct analogs of IND (-)-237D with high affinity towards α6β2* nAChR. These leads can be synthesized and tested in in vitro and in vivo studies as lead candidates for drugs to treat nicotine addiction.
Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin
Authors: Tumpara Srinu , Gründing Anna R. , Sivaraman Kokilavani , Wrenger Sabine , Olejnicka Beata , Welte Tobias , Wurm Maria J. , Pino Paco , Kiseljak Divor , Wurm Florian M. , Janciauskiene Sabina
Published: July 2021

For the treatment of severe COVID-19, supplementation with human plasma-purified α-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulatory activities. Researchers have demonstrated that an interaction between SARS-CoV-2 spike protein (S) and lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro and in vivo. Hence, we wanted to understand the potential anti-inflammatory activities of plasma-derived and recombinant AAT (recAAT) in a model of human total peripheral blood mononuclear cells (PBMCs) exposed to a combination of CHO expressed trimeric spike protein and LPS, ex vivo. We confirmed that cytokine production was enhanced in PBMCs within six hours when low levels of LPS were combined with purified spike proteins (“spike”). In the presence of 0.5 mg/mL recAAT, however, LPS/spike-induced TNF-α and IL-1β mRNA expression and protein release were significantly inhibited (by about 46–50%) relative to LPS/spike alone. Although without statistical significance, recAAT also reduced production of IL-6 and IL-8. Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation.
How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)
Authors: Bonomini Mario , Masola Valentina , Procino Giuseppe , Zammit Victor , Divino-Filho José C. , Arduini Arduino , Gambaro Giovanni
Published: July 2021

Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling—and their metabolic sequelae—on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.
Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging
Authors: Tokarz Janina , Möller Gabriele , Artati Anna , Huber Simone , Zeigerer Anja , Blaauw Bert , Adamski Jerzy , Dyar Kenneth Allen
Published: July 2021

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.
Loss Characterization of a Conventional Variable Inlet Guide Vane
Authors: Frank Roman G. , Wacker Christian , Niehuis Reinhard
Published: July 2021

Variable inlet guide vanes (VIGVs) are most commonly used as the major control unit of integrally geared centrifugal compressors (IGCCs). In order to enhance the efficient operating range of the compressor, the loss mechanisms and utilization limits of state-of-the-art VIGVs need to be better understood. Field measurements in the wake of a typical, commercially used configuration were therefore conducted at the VIGV test facility of the Bundeswehr University Munich. The investigations were carried out at application oriented subsonic flow conditions and stagger angles from 50∘ to 90∘ covering the full low-loss operating range, including the limits of efficient operation. For a precise local loss characterization, an inflow correlation was developed and applied to consider total pressure inhomogeneities caused by the radial inflow velocity profile and minor circumferential velocity deviations. Contrary to previous research efforts, not only the profile losses, but also the secondary flow losses induced by the open blade tips and wall-blade interactions were resolved in full detail. For this reason, a more precise and comprehensive loss assessment of realistic VIGV cascades is acquired.
UNBODY: A Poetry Escape Room in Augmented Reality
Authors: Wild Fridolin , Marshall Lawrence , Bernard Jay , White Eric , Twycross John
Published: July 2021

The integration of augmented reality (AR) technology into personal computing is happening fast, and augmented workplaces for professionals in areas such as Industry 4.0 or digital health can reasonably be expected to form liminal zones that push the boundary of what currently possible. The application potential in the creative industries, however, is vast and can target broad audiences, so with UNBODY, we set out to push boundaries of a different kind and depart from the graphic-centric worlds of AR to explore textual and aural dimensions of an extended reality, in which words haunt and re-create our physical selves. UNBODY is an AR installation for smart glasses that embeds poetry in the user’s surroundings. The augmented experience turns reality into a medium where holographic texts and film clips spill from dayglow billboards and totems. In this paper, we develop a blueprint for an AR escape room dedicated to the spoken and written word, with its open source code facilitating uptake by others into existing or new AR escape rooms. We outline the user-centered process of designing, building, and evaluating UNBODY. More specifically, we deployed a system usability scale (SUS) and a spatial interaction evaluation (SPINE) in order to validate its wider applicability. In this paper, we also describe the composition and concept of the experience, identifying several components (trigger posters, posters with video overlay, word dropper totem, floating object gallery, and a user trail visualization) as part of our first version before evaluation. UNBODY provides a sense of situational awareness and immersivity from inside an escape room. The recorded average mean for the SUS was 59.7, slightly under the recommended 68 average but still above ‘OK’ in the zone of low marginal acceptable. The findings for the SPINE were moderately positive, with the highest scores for output modalities and navigation support. This indicated that the proposed components and escape room concept work. Based on these results, we improved the experience, adding, among others, an interactive word composer component. We conclude that a poetry escape room is possible, outline our co-creation process, and deliver an open source technical framework as a blueprint for adding enhanced support for the spoken and written word to existing or coming AR escape room experiences. In an outlook, we discuss additional insight on timing, alignment, and the right level of personalization.
Factors Influencing the Distribution of Endemic Damselflies in Vanuatu
Authors: Saxton Natalie A. , Paxman Erica M. , Dean Abigail M. , Jensen Colin R. , Powell Gareth S. , Bybee Seth M.
Published: July 2021

Vanuatubasis Ober and Staniczek is a genus of damselfly endemic to Vanuatu. Little is known about the distribution and general natural history of the genus. We present the results of 14 weeks of fieldwork in Vanuatu to provide a better understanding of the biology of this genus. Specifically, we tested ecological niche models to predict the presence of Vanuatubasis throughout the region and explored how water pH may play a role in their distribution and ecology. The results of this fieldwork refined our model and further predicted the presence of this genus on additional islands. We also found stream pH as a strong predictor for the presence of Vanuatubasis, with their presence in alkaline streams significantly higher (p < 0.001). The mean pH for those streams where the genus was collected was 8.44 (n = 53).
Not Seeing the Mites for the Hairs. Comment on Möth et al. Unexpected Effects of Local Management and Landscape Composition on Predatory Mites and Their Food Resources in Vineyards. Insects 2021, 12, 180
Authors: Schausberger Peter
Published: July 2021

Möth et al. (2021) [...]
The Key Lnc (RNA)s in Cardiac and Skeletal Muscle Development, Regeneration, and Disease
Authors: Pinheiro Amanda , Naya Francisco J.
Published: July 2021

Non-coding RNAs (ncRNAs) play a key role in the regulation of transcriptional and epigenetic activity in mammalian cells. Comprehensive analysis of these ncRNAs has revealed sophisticated gene regulatory mechanisms which finely tune the proper gene output required for cellular homeostasis, proliferation, and differentiation. However, this elaborate circuitry has also made it vulnerable to perturbations that often result in disease. Among the many types of ncRNAs, long non-coding RNAs (lncRNAs) appear to have the most diverse mechanisms of action including competitive binding to miRNA targets, direct binding to mRNA, interactions with transcription factors, and facilitation of epigenetic modifications. Moreover, many lncRNAs display tissue-specific expression patterns suggesting an important regulatory role in organogenesis, yet the molecular mechanisms through which these molecules regulate cardiac and skeletal muscle development remains surprisingly limited. Given the structural and metabolic similarities of cardiac and skeletal muscle, it is likely that several lncRNAs expressed in both of these tissues have conserved functions in establishing the striated muscle phenotype. As many aspects of regeneration recapitulate development, understanding the role lncRNAs play in these processes may provide novel insights to improve regenerative therapeutic interventions in cardiac and skeletal muscle diseases. This review highlights key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle. Finally, we highlight lncRNAs encoded by imprinted genes in striated muscle and the contributions of these loci on the regulation of gene expression.
Risk Factors of Urothelial Cancer in Inflammatory Bowel Disease
Authors: Caviglia Gian Paolo , Martini Giorgio , Armandi Angelo , Rosso Chiara , Vernero Marta , Bugianesi Elisabetta , Astegiano Marco , Saracco Giorgio Maria , Ribaldone Davide Giuseppe
Published: July 2021

Extraintestinal cancers are important complications in patients with inflammatory bowel disease (IBD). A limited number of publications are available regarding the association between IBD and urothelial cancer. The primary outcome of our study was the comparison of the prevalence of urothelial cancer in patients with IBD with respect to the prevalence in the general population. Secondary outcomes were the assessment of risk factors for the onset of urothelial cancer in IBD. In a retrospective study we examined the medical records of all patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2021. For each of the patients with identified urothelial cancer, more than ten patients without cancer were analyzed. Furthermore, 5739 patients with IBD were analyzed and 24 patients diagnosed with urothelial cancer were identified. The incidence of urothelial cancer, compared with the incidence in the general population, was not significantly different (0.42% vs. 0.42%; p = 0.98). Twenty-three cases were then compared (1 case was discarded due to lack of follow-up data) against 250 controls. During the multivariate analysis, smoking (odds ratio, OR = 8.15; 95% confidence interval, CI = 1.76–37.63; p = 0.007) and male sex (OR = 4.04; 95% CI = 1.29–12.66; p = 0.016) were found as risk factors. In conclusion, patients with IBD have a similar risk of developing urothelial cancer compared to the general population, but males with a history of smoking are at increased risk.
Gastric Microenvironment—A Partnership between Innate Immunity and Gastric Microbiota Tricks Helicobacter pylori
Authors: Mărginean Cristina Oana , Meliț Lorena Elena , Săsăran Maria Oana
Published: July 2021

Helicobacter pylori (H. pylori) carcinogenicity depends on three major factors: bacterial virulence constituents, environmental factors and host’s genetic susceptibility. The relationship between microenvironmental factors and H. pylori virulence factors are incontestable. H. pylori infection has a major impact on both gastric and colonic microbiota. The presence of non-H. pylori bacteria within the gastric ecosystem is particularly important since they might persistently act as an antigenic stimulus or establish a partnership with H. pylori in order to augment the subsequent inflammatory responses. The gastric ecosystem, i.e., microbiota composition in children with H. pylori infection is dominated by Streptoccocus, Neisseria, Rothia and Staphylococcus. The impairment of this ecosystem enhances growth and invasion of different pathogenic bacteria, further impairing the balance between the immune system and mucosal barrier. Moreover, altered microbiota due to H. pylori infection is involved in increasing the gastric T regulatory cells response in children. Since gastric homeostasis is defined by the partnership between commensal bacteria and host’s immune system, this review is focused on how pathogen recognition through toll-like receptors (TLRs—an essential class of pathogen recognition receptors—PRRs) on the surface of macrophages and dendritic cells impact the immune response in the setting of H. pylori infection. Further studies are required for delineate precise role of bacterial community features and of immune system components.
New Closure Method Using Loop and Open–Close Clips after Endoscopic Submucosal Dissection of Stomach and Colon Lesions
Authors: Yoshida Akira , Kurumi Hiroki , Ikebuchi Yuichiro , Kawaguchi Koichiro , Yashima Kazuo , Kamitani Yu , Yasui Sho , Nakada Yusuke , Kanda Tsutomu , Takata Tomoaki , Isomoto Hajime
Published: July 2021

Endoscopic submucosal dissection (ESD) and en bloc resection of stomach and colon tumors have become common. However, mucosal defects resulting from ESD may cause delayed bleeding and perforation. To prevent adverse events, we developed a new clip closure technique, namely, the loop and open–close clip closure method (LOCCM), and aimed to examine its efficacy after ESD for stomach and colon tumors. The LOCCM uses loop and open–close clips. Here, the open–close clip was used to grasp the loop to bring it to the edge of the post-ESD mucosal defect. Another clip with a loop was then inserted into the opposite edge and clipped to the contralateral mucosa to pull both edges together. Once apposed, additional clips facilitated complete closure. The LOCCM was performed in 19 patients after ESD at Tottori University between October 2020 and March 2021. The outcomes retrospectively analyzed were the LOCCM success and adverse event rates. The complete closure rate using LOCCM was 89.5% and none of the patients had post-ESD bleeding or perforation. The results show that LOCCM is an effective and safe closure technique for mucosal defects after stomach and colon ESD to prevent bleeding and perforation.
Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited
Authors: Kołbuc Marcin , Bieniaś Beata , Habbig Sandra , Kołek Mateusz F. , Szczepańska Maria , Kiliś-Pstrusińska Katarzyna , Wasilewska Anna , Adamczyk Piotr , Motyka Rafał , Tkaczyk Marcin , Sikora Przemysław , Beck Bodo B. , Zaniew Marcin
Published: July 2021

Background: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). Methods: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. Results: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. Conclusions: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.
Efficacy of Transcutaneous Spinal Stimulation versus Whole Body Vibration for Spasticity Reduction in Persons with Spinal Cord Injury
Authors: Sandler Evan B. , Condon Kyle , Field-Fote Edelle C.
Published: July 2021

Transcutaneous spinal stimulation (TSS) and whole-body vibration (WBV) each have a robust ability to activate spinal afferents. Both forms of stimulation have been shown to influence spasticity in persons with spinal cord injury (SCI), and may be viable non-pharmacological approaches to spasticity management. In thirty-two individuals with motor-incomplete SCI, we used a randomized crossover design to compare single-session effects of TSS versus WBV on quadriceps spasticity, as measured by the pendulum test. TSS (50 Hz, 400 μs, 15 min) was delivered in supine through a cathode placed over the thoracic spine (T11-T12) and an anode over the abdomen. WBV (50 Hz; eight 45-s bouts) was delivered with the participants standing on a vibration platform. Pendulum test first swing excursion (FSE) was measured at baseline, immediately post-intervention, and 15 and 45 min post-intervention. In the whole-group analysis, there were no between- or within-group differences of TSS and WBV in the change from baseline FSE to any post-intervention timepoints. Significant correlations between baseline FSE and change in FSE were associated with TSS at all timepoints. In the subgroup analysis, participants with more pronounced spasticity showed significant decreases in spasticity immediately post-TSS and 45 min post-TSS. TSS and WBV are feasible physical therapeutic interventions for the reduction of spasticity, with persistent effects.
Hospitalisation for Drug Infusion Did Not Increase Levels of Anxiety and the Risk of Disease Relapse in Patients with Inflammatory Bowel Disease during COVID-19 Outbreak
Authors: Bertani Lorenzo , Barberio Brigida , Tricò Domenico , Zanzi Federico , Maniero Daria , Ceccarelli Linda , Marsilio Ilaria , Coppini Francesca , Lorenzon Greta , Mumolo Maria Gloria , Zingone Fabiana , Costa Francesco , Savarino Edoardo Vincenzo
Published: July 2021

During the coronavirus disease 2019 (COVID-19) pandemic, immunomodulatory therapies and hospital admission were suspected to increase the risk of infection. Nevertheless, patients with inflammatory bowel diseases (IBD) treated with intravenous (i.v.) biologics had to move to hospitals for drug infusion. We investigated the impact of hospitalisation in patients with IBD. We conducted a survey including consecutive IBD patients initially in clinical and biochemical remission treated with biologics at the end of the first lockdown period. Patients underwent the normally scheduled clinical visits, performed at hospital for i.v.-treated patients or at home for patients treated with s.c. drugs. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 12 questions, specifically related to COVID-19 and its implications. A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. No relapses were recorded in either group (hospitalized vs. non-hospitalized, p = ns), as well as which, COVID-19 infections were not demonstrated in patients in contact with people with suspected symptoms or directly experiencing them. The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs. 37.2 ± 2.8; p = 0.98). In patients treated with i.v. drugs receiving a televisit (n = 17), the rate of satisfaction with telemedicine (58.8%) was significantly lower compared with those treated with s.c. drugs (94.8%; p < 0.0005). Our results suggest that hospitalisation during the COVID-19 outbreak does not increase the risk of COVID-19 infection as well as the risk of IBD relapse; moreover, the similar levels of anxiety in both groups could confirm that there is no need to convert patients from i.v. to s.c. therapy.
Intravenous Tranexamic Acid Has Benefit for Reducing Blood Loss after Open-Wedge High Tibial Osteotomy: A Randomized Controlled Trial
Authors: Kim Man-Soo , Koh In-Jun , Sung Yong-Gyu , Park Dong-Chul , Ha Won-Jun , In Yong
Published: July 2021

(1) Background: the purpose of this study was to investigate the efficacy and safety of intravenous (IV) administration of tranexamic acid (TXA) in patients undergoing medial opening wedge high tibial osteotomy (MOWHTO). (2) Methods: a total of 73 patients were randomly allocated into two groups (TXA group and control group). The primary outcome was total perioperative calculated blood loss after MOWHTO. Secondary outcomes included self-reported pain severity using a 10-point visual analog scale (VAS) and the EuroQol-5 Dimension (EQ-5D) questionnaire. The postoperative allogeneic transfusion rate and wound complications were compared. Deep vein thrombosis (DVT) incidence was compared by conducting DVT computed tomography imaging. (3) Results: the total blood loss after surgery was 470.9 mL in the TXA group and 739.3 mL in the control group, showing a significant difference (p < 0.001). There were no differences in pain VAS scores between the two groups (all p > 0.05). No difference in preoperative EQ-5D scores for any items existed between the two groups. No transfusion was performed in either group. There was no difference in DVT incidence or the rate of wound complications between the two groups. (4) Conclusion: in patients undergoing MOWHTO, IV TXA reduces total blood loss and drainage amount. However, no additional benefits in clinical outcomes, transfusion rate, or wound complications were apparent, with similar DVT incidence rates.
Compressed Sensing Real-Time Cine Reduces CMR Arrhythmia-Related Artifacts
Authors: Longère Benjamin , Allard Paul-Edouard , Gkizas Christos V , Coisne Augustin , Hennicaux Justin , Simeone Arianna , Schmidt Michaela , Forman Christoph , Toupin Solenn , Montaigne David , Pontana François
Published: July 2021

Background and objective: Cardiac magnetic resonance (CMR) is a key tool for cardiac work-up. However, arrhythmia can be responsible for arrhythmia-related artifacts (ARA) and increased scan time using segmented sequences. The aim of this study is to evaluate the effect of cardiac arrhythmia on image quality in a comparison of a compressed sensing real-time (CSrt) cine sequence with the reference prospectively gated segmented balanced steady-state free precession (Cineref) technique regarding ARA. Methods: A total of 71 consecutive adult patients (41 males; mean age = 59.5 ± 20.1 years (95% CI: 54.7–64.2 years)) referred for CMR examination with concomitant irregular heart rate (defined by an RR interval coefficient of variation >10%) during scanning were prospectively enrolled. For each patient, two cine sequences were systematically acquired: first, the reference prospectively triggered multi-breath-hold Cineref sequence including a short-axis stack, one four-chamber slice, and a couple of two-chamber slices; second, an additional single breath-hold CSrt sequence providing the same slices as the reference technique. Two radiologists independently assessed ARA and image quality (overall, acquisition, and edge sharpness) for both techniques. Results: The mean heart rate was 71.8 ± 19.0 (SD) beat per minute (bpm) (95% CI: 67.4–76.3 bpm) and its coefficient of variation was 25.0 ± 9.4 (SD) % (95% CI: 22.8–27.2%). Acquisition was significantly faster with CSrt than with Cineref (Cineref: 556.7 ± 145.4 (SD) s (95% CI: 496.7–616.7 s); CSrt: 23.9 ± 7.9 (SD) s (95% CI: 20.6–27.1 s); p < 0.0001). A total of 599 pairs of cine slices were evaluated (median: 8 (range: 6–14) slices per patient). The mean proportion of ARA-impaired slices per patient was 85.9 ± 22.7 (SD) % using Cineref, but this was figure was zero using CSrt (p < 0.0001). The European CMR registry artifact score was lower with CSrt (median: 1 (range: 0–5)) than with Cineref (median: 3 (range: 0–3); p < 0.0001). Subjective image quality was higher in CSrt than in Cineref (median: 3 (range: 1–3) versus 2 (range: 1–4), respectively; p < 0.0001). In line, edge sharpness was higher on CSrt cine than on Cineref images (0.054 ± 0.016 pixel−1 (95% CI: 0.050–0.057 pixel−1) versus 0.042 ± 0.022 pixel−1 (95% CI: 0.037–0.047 pixel−1), respectively; p = 0.0001). Conclusion: Compressed sensing real-time cine drastically reduces arrhythmia-related artifacts and thus improves cine image quality in patients with arrhythmia.
Airway Abnormalities in Adult Mucopolysaccharidosis and Development of Salford Mucopolysaccharidosis Airway Score
Authors: Gadepalli Chaitanya , Stepien Karolina M. , Sharma Reena , Jovanovic Ana , Tol Govind , Bentley Andrew
Published: July 2021

(1) Background: Mucopolysaccharidoses (MPS) are a heterogeneous group of lysosomal storage disorders caused by the absence of enzymes required for degradation of glycosaminoglycans (GAGs). GAGs deposition in tissues leads to progressive airway narrowing and/or tortuosity. Increased longevity of patients has posed newer problems, especially the airway. This study aims to characterise various airway abnormalities in adult MPS from a regional centre and proposes a method to quantify the severity of the airway disease. (2) Methods: Retrospective analysis by case notes review, clinical examination, endoscopy, cross-sectional imaging, 3-dimensional reconstruction, and physiological investigations were used to assess the airway abnormalities. Quantitative assessment of the airway severity was performed a validated questionnaire of 15 parameters to derive Salford Mucopolysaccharidosis Airway Score (SMAS). (3) Results: Thirty-one adult MPS patients (21M/ 9F; median 26.7 years; range 19–42 years) were reviewed. There were 9 MPS I, 12 MPS II, 2 MPS III, 5 MPS IV, 2 MPS VI, and 1 MPS VII. Airway abnormalities in each MPS type are described. Patients scoring more than 35 on SMAS had some form of airway intervention. The area under curve of 0.9 was noted at a score of 25, so SMAS more than 25 may predict a difficult airway and potential to have complications. Pearson’s correlation between SMAS and height, weight, BMI were poor (p < 0.05). (4) Conclusions: Airway abnormalities in adult MPS are varied and complex. Assessment of the airway should be holistic and include multiple parameters. An objective multidimensional score such as SMAS may help to predict and manage difficult airways warranting further investigation and validation.
Impact on Visual Acuity in Neovascular Age Related Macular Degeneration (nAMD) in Europe Due to COVID-19 Pandemic Lockdown
Authors: Arruabarrena Carolina , Toro Mario Damiano , Onen Mehmet , Malyugin Boris E , Rejdak Robert , Tognetto Danielle , Zweifel Sandrine , Giglio Rosa , Teus Miguel A
Published: July 2021

This is a retrospective, multicenter study of consecutive patients with nAMD scheduled for a visit and/or a treatment with an intravitreal injection (IVI) during the 3 months before lockdown in the Ophthalmology Departments of six centers of Europe.The study was conducted on 546 patients, of which 55.13% were females, almost 100% of the patients were White/Caucasian race, and 71.53% of the patients presented a type 1 macular neovascularization (NVM). A total of 62.82% of patients (343 patients) that were on scheduled clinic visits and/or intravitreal injection treatment during the 3 months before the quarantine did not attend either to visit or for treatment during the lockdown. The mean number of injections during the lockdown was significantly reduced. This was followed by a significant reduction in the mean best-corrected visual acuity (BCVA) between the 3 months before the lockdown (mean BCVA of 60.68 ± 19.77 letters) and 6 months after lockdown (mean BCVA of 56.98 ± 22.59 letters). Patients with better BCVA before the lockdown and the ones showing neovascular activity were more likely to attend their scheduled visits and/or IVI treatments. The COVID-19 pandemic and the lockdown have led to a decrease in the number of IVI treatments in patients with nAMD, evidencing a significant vision loss at 6 months.
Antibiotic De-escalation Experience in the Setting of Emergency Department: A Retrospective, Observational Study
Authors: Corcione Silvia , Mornese Pinna Simone , Lupia Tommaso , Trentalange Alice , Germanò Erika , Cavallo Rossana , Lupia Enrico , De Rosa Francesco Giuseppe
Published: July 2021

Background: Antimicrobial de-escalation (ADE) is a part of antimicrobial stewardship strategies aiming to minimize unnecessary or inappropriate antibiotic exposure to decrease the rate of antimicrobial resistance. Information regarding the effectiveness and safety of ADE in the setting of emergency medicine wards (EMW) is lacking. Methods: Adult patients admitted to EMW and receiving empiric antimicrobial treatment were retrospectively studied. The primary outcome was the rate and timing of ADE. Secondary outcomes included factors associated with early ADE, length of stay, and in-hospital mortality. Results: A total of 336 patients were studied. An initial regimen combining two agents was prescribed in 54.8%. Ureidopenicillins and carbapenems were the most frequently empiric treatment prescribed (25.1% and 13.6%). The rate of the appropriateness of prescribing was 58.3%. De-escalation was performed in 111 (33%) patients. Patients received a successful de-escalation on day 2 (21%), 3 (23%), and 5 (56%). The overall in-hospital mortality was 21%, and it was significantly lower among the de-escalation group than the continuation group (16% vs 25% p = 0.003). In multivariate analysis, de-escalation strategies as well as appropriate empiric and targeted therapy were associated with reduced mortality. Conclusions: ADE appears safe and effective in the setting of EMWs despite that further research is warranted to confirm these findings.
Improved Prognostic Value in Predicting Long-Term Cardiovascular Events by a Combination of High-Sensitivity C-Reactive Protein and Brachial–Ankle Pulse Wave Velocity
Authors: Kim Hack-Lyoung , Lim Woo-Hyun , Seo Jae-Bin , Kim Sang-Hyun , Zo Joo-Hee , Kim Myung-A
Published: July 2021

Background: Both C-reactive protein (CRP) and arterial stiffness are associated with the development of cardiovascular disease (CVD). This study was performed to investigate whether a combination of these two measurements could improve cardiovascular risk stratification. Methods: A total of 6572 consecutive subjects (mean age, 60.8 ± 11.8 years; female, 44.2%) who underwent both high-sensitivity CRP (hs-CRP) and brachial–ankle pulse wave velocity (baPWV) measurement within 1 week were retrospectively analyzed. Major adverse cardiovascular events (MACE), including cardiovascular death, acute myocardial infarction, coronary revascularization, and stroke were assessed during the clinical follow-up. Results: During a mean follow-up period of 3.75 years (interquartile range, 1.78–5.31 years), there were 182 cases of MACE (2.8%). The elevated baPWV (≥1505 cm/s) (hazard ratio (HR), 4.21; 95% confidence interval (CI), 2.73–6.48; p < 0.001) and hs-CRP (≥3 mg/L) (HR, 1.57; 95% CI, 1.12–2.21; p < 0.001) levels were associated with MACE even after controlling for potential confounders. The combination of baPWV and hs-CRP further stratified the subjects’ risk (subjects with low baPWV and hs-CRP vs. subjects with high baPWV and hs-CRP; HR, 7.08; 95% CI, 3.76−13.30; p < 0.001). Adding baPWV information to clinical factors and hs-CRP had an incremental prognostic value (global Chi-square score, from 126 to 167, p < 0.001). Conclusions: The combination of hs-CRP and baPWV provided a better prediction of future CVD than either one by itself. Taking these two simple measurements simultaneously is clinically useful in cardiovascular risk stratification.
Numerical Investigation to the Effect of Suction-Induced Seepage on the Settlement in the Underwater Vacuum Preloading with Prefabricated Vertical Drains
Authors: Lin Shu , Fu Dengfeng , Zhou Zefeng , Yan Yue , Yan Shuwang
Published: July 2021

Vacuum preloading combined with prefabricated vertical drains (PVDs) has the potential to improve the soft sediments under water, however, its development is partly limited by the unclear understanding of the mechanism. This paper aims to extend the comprehension of the influential mechanism of overlapping water in the scenario of underwater vacuum preloading with PVDs. The systematic investigations were conducted by small strain finite element drained analyses, with the separated analysis schemes considering suction-induced consolidation, seepage and their combination. The development of settlement in the improved soil region and the evolution of seepage flow from the overlapping water through the non-improved soil region into improved zone are examined in terms of the build-up of excess pore pressure. Based on the results of numerical analyses, a theoretical approach was set out. It was capable to estimate the time-dependent non-uniform settlement along the improved soil surface in response to the combined effects of suction-induced consolidation and seepage. The difference of underwater and onshore vacuum preloading with PVDs is discussed with some practical implication and suggestion provided.
Destruxin A Interacts with Aminoacyl tRNA Synthases in Bombyx mori
Authors: Wang Jingjing , Berestetskiy Alexander , Hu Qiongbo
Published: July 2021

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin produced by the entomopathogenic fungus Metarhizium anisopliae, exhibits insecticidal activities in a wide range of pests and is known as an innate immunity inhibitor. However, its mechanism of action requires further investigation. In this research, the interactions of DA with the six aminoacyl tRNA synthetases (ARSs) of Bombyx mori, BmAlaRS, BmCysRS, BmMetRS, BmValRS, BmIleRS, and BmGluProRS, were analyzed. The six ARSs were expressed and purified. The BLI (biolayer interferometry) results indicated that DA binds these ARSs with the affinity indices (KD) of 10−4 to 10−5 M. The molecular docking suggested a similar interaction mode of DA with ARSs, whereby DA settled into a pocket through hydrogen bonds with Asn, Arg, His, Lys, and Tyr of ARSs. Furthermore, DA treatments decreased the contents of soluble protein and free amino acids in Bm12 cells, which suggested that DA impedes protein synthesis. Lastly, the ARSs in Bm12 cells were all downregulated by DA stress. This study sheds light on exploring and answering the molecular target of DA against target insects.
Species Distribution of Candidemia and Their Susceptibility in a Single Japanese University Hospital: Prior Micafungin Use Affects the Appearance of Candida parapsilosis and Elevation of Micafungin MICs in Non-parapsilosis Candida Species
Authors: Sakamoto Yasutaka , Kawabe Kazuhiro , Suzuki Tomoyo , Sano Kayoko , Ide Kazuo , Nishigaki Tetsuta , Enoki Yuki , Taguchi Kazuaki , Koike Hirofumi , Kato Hideaki , Sahashi Yukiko , Matsumoto Kazuaki
Published: July 2021

Introduction: Micafungin is a recommended echinocandin antifungal agent for candidemia treatment and prophylaxis. However, overuse of echinocandin antifungals may cause resistance. There is currently no information available regarding the low susceptibility associated with using micafungin. This study investigated the effect of micafungin use on changes in the detected Candida species and low susceptibility. Methods: We conducted a retrospective survey and included records of Candida spp. detected in blood cultures from January 2010 to December 2018 in our hospital. Survey items included clinical outcomes at 30 days after positive cultures, patient characteristics, and drug prescription status. Patient background information included gender, previous hospitalization, stay in the intensive care unit, comorbidities, and history of surgery (within 90 days before candidemia onset) and drug exposure. Species detected and their minimum inhibitory concentrations (MICs) and amount of antifungal prescriptions by department were investigated. Risk factors for detecting C. parapsilosis and for low susceptibility to micafungin were evaluated using multivariate analysis. Results: A total of 153 Candida clinical blood isolates were collected and C. albicans was the most prevalent species, followed by C. parapsilosis and C. glabrata. In the analysis by department, antifungal use and non-albicans Candida species were most frequently detected in the hematology department. Multivariate analysis showed that prior micafungin use increased the risk of C. parapsilosis (odds ratio (OR) 4.22; 95% confidence interval (CI) 1.39–12.79; p = 0.011). MIC90 of micafungin on C. glabrata and C. parapsilosis was 1.0 μg/mL. Prior micafungin use was clarified as a risk factor resulting in MIC > 0.06 μg/mL for micafungin in non-parapsilosis Candida species (OR 13.2; 95% CI 3.23–54.2; p < 0.01). Conclusion: Prior micafungin use increased the risk of C. parapsilosis and the MIC > 0.06 μg/mL of micafungin in non-parapsilosis Candida species. Since there are only a few antifungal options, further antifungal stewardship considering azole antifungal agents use is required.