bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Validation of cas9/GuideRNA Constructs for Site-Directed Mutagenesis of Triticale ABA8′OH1 loci
Authors: Michalski Krzysztof , Hertig Christian , Mańkowski Dariusz R. , Kumlehn Jochen , Zimny Janusz , Linkiewicz Anna M.
Published: June 2021

Cas endonuclease-mediated genome editing provides a long-awaited molecular biological approach to the modification of predefined genomic target sequences in living organisms. Although cas9/guide (g)RNA constructs are straightforward to assemble and can be customized to target virtually any site in the plant genome, the implementation of this technology can be cumbersome, especially in species like triticale that are difficult to transform, for which only limited genome information is available and/or which carry comparatively large genomes. To cope with these challenges, we have pre-validated cas9/gRNA constructs (1) by frameshift restitution of a reporter gene co-introduced by ballistic DNA transfer to barley epidermis cells, and (2) via transfection in triticale protoplasts followed by either a T7E1-based cleavage assay or by deep-sequencing of target-specific PCR amplicons. For exemplification, we addressed the triticale ABA 8′-HYDROXYLASE 1 gene, one of the putative determinants of pre-harvest sprouting of grains. We further show that in-del induction frequency in triticale can be increased by TREX2 nuclease activity, which holds true for both well- and poorly performing gRNAs. The presented results constitute a sound basis for the targeted induction of heritable modifications in triticale genes.
The Relationship between Cadmium Toxicity and the Modulation of Epigenetic Traits in Plants
Authors: Niekerk Lee-Ann , Carelse Mogamat Fahiem , Bakare Olalekan Olanrewaju , Mavumengwana Vuyo , Keyster Marshall , Gokul Arun
Published: June 2021

Elevated concentrations of heavy metals such as cadmium (Cd) have a negative impact on staple crop production due to their ability to elicit cytotoxic and genotoxic effects on plants. In order to understand the relationship between Cd stress and plants in an effort to improve Cd tolerance, studies have identified genetic mechanisms which could be important for conferring stress tolerance. In recent years epigenetic studies have garnered much attention and hold great potential in both improving the understanding of Cd stress in plants as well as revealing candidate mechanisms for future work. This review describes some of the main epigenetic mechanisms involved in Cd stress responses. We summarize recent literature and data pertaining to chromatin remodeling, DNA methylation, histone acetylation and miRNAs in order to understand the role these epigenetic traits play in cadmium tolerance. The review aims to provide the framework for future studies where these epigenetic traits may be used in plant breeding and molecular studies in order to improve Cd tolerance.
Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
Authors: Jang Jeong-Won , Kim Hye-Seon , Kim Jin-Seoub , Lee Soon-Kyu , Han Ji-Won , Sung Pil-Soo , Bae Si-Hyun , Choi Jong-Young , Yoon Seung-Kew , Han Dong-Jin , Kim Tae-Min , Roberts Lewis R.
Published: June 2021

Although hepatitis B virus (HBV) integration into the cellular genome is well known in HCC (hepatocellular carcinoma) patients, its biological role still remains uncertain. This study investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) alterations in paired tumor and non-tumor tissues. Compared to those in non-tumors, tumoral integrations occurred less frequently but with higher read counts and were more preferentially observed in genic regions with significant enrichment of integration into promoters. In HBV-related tumors, TERT promoter was identified as the most frequent site (38.5% (10/26)) of HBV integration. TERT promoter mutation was observed only in tumors (24.2% (8/33)), but not in non-tumors. Only 3.00% (34/1133) of HBV integration sites were shared between tumors and non-tumors. Within the HBV genome, HBV breakpoints were distributed preferentially in the 3’ end of HBx, with more tumoral integrations detected in the preS/S region. The major genes that were recurrently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tumors. Functional enrichment analysis of tumoral genes with integrations showed enrichment of cancer-associated genes. The patterns and functions of HBV integration are distinct between tumors and non-tumors. Tumoral integration is often enriched into both human-virus regions with oncogenic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcinogenesis.
Gene Variant of Barrier to Autointegration Factor 2 (Banf2w) Is Concordant with Female Determination in Cichlids
Authors: Curzon Arie Yehuda , Shirak Andrey , Benet-Perlberg Ayana , Naor Alon , Low-Tanne Shai Israel , Sharkawi Haled , Ron Micha , Seroussi Eyal
Published: June 2021

Oreochromis fishes exhibit variability of sex-determination (SD) genes whose characterization contributes to understanding of the sex differentiation network, and to effective tilapia farming, which requires all-male culture. However, O. niloticus (On) amh is the only master-key regulator (MKR) of SD that has been mapped (XY/XX SD-system on LG23). In O. aureus (Oa), LG3 controls a WZ/ZZ SD-system that has recently been delimited to 9.2 Mbp, with an embedded interval rich with female-specific variation, harboring two paics genes and banf2. Developing genetic markers within this interval and using a hybrid Oa stock that demonstrates no recombination repression in LG3, we mapped the critical SD region to 235 Kbp on the orthologous On physical map (p < 1.5 × 10−26). DNA-seq assembly and peak-proportion analysis of variation based on Sanger chromatograms allowed the characterization of copy-number variation (CNV) of banf2. Oa males had three exons capable of encoding 90-amino-acid polypeptides, yet in Oa females, we found an extra copy with an 89-amino-acid polypeptide and three non-conservative amino acid substitutions, designated as banf2w. CNV analysis suggested the existence of two to five copies of banf2 in diploidic Cichlidae. Disrupting the Hardy–Weinberg equilibrium (p < 4.2 × 10−3), banf2w was concordant with female determination in Oa and in three cichlids with LG3 WZ/ZZ SD-systems (O. tanganicae, O. hornorum and Pelmatolapia mariae). Furthermore, exclusive RNA-seq expression in Oa females strengthened the candidacy of banf2w as the long-sought LG3 SD MKR. As banf genes mediate nuclear assembly, chromatin organization, gene expression and gonad development, banf2w may play a fundamental role inducing female nucleus formation that is essential for WZ/ZZ SD.
Differential Response to Single and Combined Salt and Heat Stresses: Impact on Accumulation of Proteins and Metabolites in Dead Pericarps of Brassica juncea
Authors: Singiri Jeevan R. , Swetha Bupur , Sikron-Persi Noga , Grafi Gideon
Published: June 2021

Dead organs enclosing embryos, such as seed coats and pericarps, are emerging as important maternally-derived components of the dispersal unit that affect seed performance and fate. In the face of climate change and increased incidents of heatwaves, we sought to investigate the effect of salinity (S), short episodes of high temperature (HS), and combination of S + HS (SHS), at the reproductive phase, on the properties of dead pericarps of Brassica juncea. Proteome and metabolome analyses revealed multiple proteins and metabolites stored in dead pericarps whose levels and composition were altered under single and combined stress conditions. The protein profile of SHS showed a higher correlation with salt than with HS indicating the dominant effect of salt over heat stress. On the other hand, the analysis of metabolites showed that the profile of SHS has better correlation with HS than with salt. The integration of metabolic and proteomic data showed that changes in TCA cycle intermediates and certain amino acids (e.g., proline) under salt treatments (S and SHS) are highly correlated with changes in proteins involved in their biosynthetic pathways. Thus, accumulation of proteins and metabolites in dead pericarps is differently affected by single and combination of salt and heat stresses. Salinity appears to dominate plant response to combined stresses at the protein level, while heat appears to be the major factor affecting metabolite accumulation in dead pericarps.
Hyaluronan as a Prominent Biomolecule with Numerous Applications in Medicine
Authors: Valachová Katarína , Šoltés Ladislav
Published: June 2021

Hyaluronan (HA) is a natural glycosaminoglycan present in many tissues of all vertebrates. HA has various biological functions, which are dependent on its molar mass. High-molar-mass HA has anti-angiogenic, immunosuppressive and anti-inflammatory properties, while low-molar-mass HA has opposite effects. HA has also antioxidative properties, however on the other hand it can be readily degraded by reactive oxygen species. For many years it has been used in treatment of osteoarthritis, cosmetics and in ophthalmology. In the last years there has been a growing interest of HA to also be applied in other fields of medicine such as skin wound healing, tissue engineering, dentistry and gene delivery. In this review we summarize information on modes of HA administration, properties and effects of HA in various fields of medicine including recent progress in the investigation of HA.
Acellular Dermal Matrix Used in Diabetic Foot Ulcers: Clinical Outcomes Supported by Biochemical and Histological Analyses
Authors: Campitiello Ferdinando , Mancone Manfredi , Cammarota Marcella , D’Agostino Antonella , Ricci Giulia , Stellavato Antonietta , Della Corte Angela , Pirozzi Anna Virginia Adriana , Scialla Gianluca , Schiraldi Chiara , Canonico Silvestro
Published: June 2021

Diabetic foot ulcer (DFU) is a diabetes complication which greatly impacts the patient’s quality of life, often leading to amputation of the affected limb unless there is a timely and adequate management of the patient. DFUs have a high economic impact for the national health system. Data have indeed shown that DFUs are a major cause of hospitalization for patients with diabetes. Based on that, DFUs represent a very important challenge for the national health system. Especially in developed countries diabetic patients are increasing at a very high rate and as expected, also the incidence of DFUs is increasing due to longevity of diabetic patients in the western population. Herein, the surgical approach focused on the targeted use of the acellular dermal matrix has been integrated with biochemical and morphological/histological analyses to obtain evidence-based information on the mechanisms underlying tissue regeneration. In this research report, the clinical results indicated decreased postoperative wound infection levels and a short healing time, with a sound regeneration of tissues. Here we demonstrate that the key biomarkers of wound healing process are activated at gene expression level and also synthesis of collagen I, collagen III and elastin is prompted and modulated within the 28-day period of observation. These analyses were run on five patients treated with Integra® sheet and five treated with the injectable matrix Integra® Flowable, for cavitary lesions. In fact, clinical evaluation of improved healing was, for the first time, supported by biochemical and histological analyses. For these reasons, the present work opens a new scenario in DFUs treatment and follow-up, laying the foundation for a tailored protocol towards complete healing in severe pathological conditions.
Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter
Authors: Willadsen Maria , Uengoer Metin , Sługocka Anna , Schwarting Rainer K.W. , Homberg Judith R. , Wöhr Markus
Published: June 2021

Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality.
Can Spa Tourism Enhance Water Resources and Turn Them into a National Brand? A Theoretical Review about the Romanian Case
Authors: Nistoreanu Puiu , Aluculesei Alina-Cerasela
Published: June 2021

The present article includes descriptive research about how water resources in Romanian medical spas could be better promoted to increase their visibility. Romania is one of the European countries with impressive potential in terms of balneology, having a wide diversity of natural factors that allow treating several medical conditions in the same resort. In addition, one-third of the mineral and thermal water springs in Europe are present on the Romanian territory, making Romania one of the most important European destinations in terms of natural spa resources. The present research aims to illustrate how the Romanian medical spas communicate with tourists about the therapeutic water available in five medical spas: Băile Felix-1 Mai, Techirghiol, Băile Tușnad, Sovata and Covasna, having as its main objective to raise the awareness among the spas representatives regarding the necessity of water management implementation. The research is based on primary data obtained from the official websites of the resorts included in the study and in the published scholarly articles that approached the Romanian medical spas.
Long-Term Survival in Patients with or without Implantable Cardioverter Defibrillator after Transcatheter Aortic Valve Implantation
Authors: Fischer-Rasokat Ulrich , Renker Matthias , Liebetrau Christoph , Weferling Maren , Rolf Andreas , Hain Andreas , Sperzel Johannes , Choi Yeong-Hoon , Hamm Christian W. , Kim Won-Keun
Published: June 2021

Patients with symptomatic aortic stenosis (AS) can have concomitant systolic heart failure (HF) that persists even after correction of afterload by transcatheter aortic valve implantation (TAVI). These patients qualify as potential candidates for prophylactic therapy with an implantable cardioverter defibrillator (ICD). We compared survival between patients with or without an ICD after successful TAVI. This retrospective study analyzed Kaplan-Meier survival data during a follow-up period of three years in two populations: (a) patients with a left ventricular ejection fraction (LVEF) ≤ 35% before TAVI (overall population); (b) patients with additionally documented LVEF ≤ 35% 3 months after TAVI (persistent LV dysfunction subpopulation). In the overall population, 53 patients with and 193 patients without an ICD had similar baseline characteristics and procedural success rates, and HF medication at discharge was comparable. Three-year mortality rates were 26.4% for patients with an ICD and 24.4% for patients without an ICD (p = 0.758). Cardiovascular death rates were similar between groups (p = 0.914), and deaths were most often attributed to worsening of HF. Survival rates in patients with persistent LV dysfunction with an ICD (n = 24) or without an ICD (n = 59) were similar between groups (p = 0.872), with cardiovascular deaths mostly qualified as worsening HF and none as sudden cardiac death. Patients of the overall study population with biventricular pacing devices showed only a tendency to have better outcomes (p = 0.298). ICD therapy in elderly patients with AS and LV dysfunction undergoing TAVI did not demonstrate a survival benefit during a 3-year follow-up period.
The Number of Myomas Is the Most Important Risk Factor for Blood Loss and Total Operation Time in Robotic Myomectomy: Analysis of 242 Cases
Authors: Lee Sa Ra , Kim Ju Hee , Kim Sehee , Kim Sung Hoon , Chae Hee Dong
Published: June 2021

To identify factors affecting blood loss and operation time (OT) during robotic myomectomy (RM), we reviewed a total of 448 patients who underwent RM at Seoul Asan Hospital between 1 January 2019, and 28 February 2021, at Seoul Asan Hospital. To avoid variations in surgical proficiency, only 242 patients managed by two surgeons who each performed >80 RM procedures during the study period were included in this study. All cases of RM were performed with a reduced port technique. We obtained the following data from each patient’s medical chart: age, gravidity, parity, body mass index, and history of previous abdominal surgery including cesarean section. We also collected information on the maximal diameter and type of myomas, number and weight of removed myomas, concomitant surgery, total OT from skin incision to closure, estimated blood loss (EBL), and blood transfusion. Data on preoperative use of gonadotropin-releasing hormone agonists (GnRHas) and perioperative use of hemostatic agents (tranexamic acid or vasopressin) were also collected. Data on the length of hospital stay, postoperative fever within 48 h, and any complications related to RM were also obtained. The primary endpoint in this study was the identification of factors affecting EBL and the secondary endpoint was the identification of factors affecting the total OT during multiport RM. Univariate and multivariate analyses were used to identify the factors affecting EBL and OT during multiport RM. The medians of the maximal diameter and weight of the removed myomas were 9.00 (interquartile range [IQR], 7.00 to 10.00) cm and 249.75 (IQR, 142.88 to 401.00) g, respectively. The median number of myomas was two (IQR, one to four), ranging from 1 to 34. Of the cases, 155 had low EBL and 87 had high EBL. Most myomas were of the intramural type (n = 179). The odds of EBL > 320 mL increased by 251% (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.16–5.42) for five to nine myomas and by 647% (OR, 6.47; 95% CI, 1.87–22.33) for ≥10 myomas. The odds of subserosal-type myomas decreased by 67% compared with intramural-type myomas (OR, 0.33; 95% CI, 0.14–0.80). History of abdominal surgery other than cesarean section was positively correlated with EBL. The weight of the removed myomas and a history of previous cesarean section were not correlated with the EBL. Conclusion: The number of myomas (5–9 and ≥10), maximal myoma diameter, and history of abdominal surgery other than cesarean section affect the EBL in RM.
Effects of External Laryngeal Manipulation on Cervical Spine Motion during Videolaryngoscopic Intubation under Manual In-Line Stabilization: A Randomized Crossover Trial
Authors: Kim Yoon Jung , Hur Chahnmee , Yoon Hyun-Kyu , Lee Hyung-Chul , Park Hee-Pyoung , Oh Hyongmin
Published: June 2021

We hypothesized that external laryngeal manipulation would reduce cervical spine motion during video laryngoscopic intubation under manual in-line stabilization by reducing the force required to lift the videolaryngoscope. In this randomized crossover trial, 27 neurointerventional patients underwent two consecutive videolaryngoscopic intubation attempts under manual in-line stabilization. External laryngeal manipulation was applied to all patients in either the first or second attempt. In the second attempt, we tried to reproduce the percentage of glottic opening score obtained in the first attempt. Primary outcomes were cervical spine motion during intubation at the occiput-C1, C1–C2, and C2–C5 segments. The intubation success rate (secondary outcome measure) was recorded. Cervical spine motion during intubation at the occiput-C1 segment was significantly smaller with than without external laryngeal manipulation (7.4° ± 4.6° vs. 11.5° ± 4.8°, mean difference −4.1° (98.33% confidence interval −5.8° to −2.3°), p < 0.001), showing a reduction of 35.7%. Cervical spine motion during intubation at the other segments was not significantly different with versus without external laryngeal manipulation. All intubations were achieved successfully regardless of the application of external laryngeal manipulation. External laryngeal manipulation is a useful method to reduce upper cervical spine motion during videolaryngoscopic intubation under manual in-line stabilization.
Transferrin Isoforms, Old but New Biomarkers in Hereditary Fructose Intolerance
Authors: Cano Ainara , Alcalde Carlos , Belanger-Quintana Amaya , Cañedo-Villarroya Elvira , Ceberio Leticia , Chumillas-Calzada Silvia , Correcher Patricia , Couce María Luz , García-Arenas Dolores , Gómez Igor , Hernández Tomás , Izquierdo-García Elsa , Martínez Chicano Dámaris , Morales Montserrat , Pedrón-Giner Consuelo , Petrina Jáuregui Estrella , Peña-Quintana Luis , Sánchez-Pintos Paula , Serrano-Nieto Juliana , Unceta Suarez María , Vitoria Miñana Isidro , de las Heras Javier
Published: June 2021

Hereditary Fructose Intolerance (HFI) is an autosomal recessive inborn error of metabolism characterised by the deficiency of the hepatic enzyme aldolase B. Its treatment consists in adopting a fructose-, sucrose-, and sorbitol (FSS)-restrictive diet for life. Untreated HFI patients present an abnormal transferrin (Tf) glycosylation pattern due to the inhibition of mannose-6-phosphate isomerase by fructose-1-phosphate. Hence, elevated serum carbohydrate-deficient Tf (CDT) may allow the prompt detection of HFI. The CDT values improve when an FSS-restrictive diet is followed; however, previous data on CDT and fructose intake correlation are inconsistent. Therefore, we examined the complete serum sialoTf profile and correlated it with FSS dietary intake and with hepatic parameters in a cohort of paediatric and adult fructosemic patients. To do so, the profiles of serum sialoTf from genetically diagnosed HFI patients on an FSS-restricted diet (n = 37) and their age-, sex- and body mass index-paired controls (n = 32) were analysed by capillary zone electrophoresis. We found that in HFI patients, asialoTf correlated with dietary intake of sucrose (R = 0.575, p < 0.001) and FSS (R = 0.475, p = 0.008), and that pentasialoTf+hexasialoTf negatively correlated with dietary intake of fructose (R = −0.386, p = 0.024) and FSS (R = −0.400, p = 0.019). In addition, the tetrasialoTf/disialoTf ratio truthfully differentiated treated HFI patients from healthy controls, with an area under the ROC curve (AUROC) of 0.97, 92% sensitivity, 94% specificity and 93% accuracy.
Measurement of Electrical Impedance Tomography-Based Regional Ventilation Delay for Individualized Titration of End-Expiratory Pressure
Authors: Muders Thomas , Hentze Benjamin , Kreyer Stefan , Wodack Karin Henriette , Leonhardt Steffen , Hedenstierna Göran , Wrigge Hermann , Putensen Christian
Published: June 2021

Rationale: Individualized positive end-expiratory pressure (PEEP) titration might be beneficial in preventing tidal recruitment. To detect tidal recruitment by electrical impedance tomography (EIT), the time disparity between the regional ventilation curves (regional ventilation delay inhomogeneity [RVDI]) can be measured during controlled mechanical ventilation when applying a slow inflation of 12 mL/kg of body weight (BW). However, repeated large slow inflations may result in high end-inspiratory pressure (PEI), which might limit the clinical applicability of this method. We hypothesized that PEEP levels that minimize tidal recruitment can also be derived from EIT-based RVDI through the use of reduced slow inflation volumes. Methods: Decremental PEEP trials were performed in 15 lung-injured pigs. The PEEP level that minimized tidal recruitment was estimated from EIT-based RVDI measurement during slow inflations of 12, 9, 7.5, or 6 mL/kg BW. We compared RVDI and PEI values resulting from different slow inflation volumes and estimated individualized PEEP levels. Results: RVDI values from slow inflations of 12 and 9 mL/kg BW showed excellent linear correlation (R2 = 0.87, p < 0.001). Correlations decreased for RVDI values from inflations of 7.5 (R2 = 0.68, p < 0.001) and 6 (R2 = 0.42, p < 0.001) mL/kg BW. Individualized PEEP levels estimated from 12 and 9 mL/kg BW were comparable (bias −0.3 cm H2O ± 1.2 cm H2O). Bias and scatter increased with further reduction in slow inflation volumes (for 7.5 mL/kg BW, bias 0 ± 3.2 cm H2O; for 6 mL/kg BW, bias 1.2 ± 4.0 cm H2O). PEI resulting from 9 mL/kg BW inflations were comparable with PEI during regular tidal volumes. Conclusions: PEEP titration to minimize tidal recruitment can be individualized according to EIT-based measurement of the time disparity of regional ventilation courses during slow inflations with low inflation volumes. This sufficiently decreases PEI and may reduce potential clinical risks.
Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia
Authors: Bordon Jose , Akca Ozan , Furmanek Stephen , Cavallazzi Rodrigo Silva , Suliman Sally , Aboelnasr Amr , Sinanova Bettina , Ramirez Julio A.
Published: June 2021

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.
First Evaluation of a New Dynamic Scoring System Intended to Support Prescription of Adjuvant CytoSorb Hemoadsorption Therapy in Patients with Septic Shock
Authors: Kogelmann Klaus , Hübner Tobias , Schwameis Franz , Drüner Matthias , Scheller Morten , Jarczak Dominik
Published: June 2021

Introduction: Despite advances in critical care medicine, adjunctive approaches in sepsis therapy have failed to prove their efficacy. Notwithstanding promising results using hemoadsorption (CytoSorb), questions remain concerning timing and dosing. We created a dynamic scoring system (DSS) to assess patients with early septic shock and performed a first evaluation of the system in this patient population. Methods: Data from 502 patients with septic shock according to Sepsis-3 criteria were retrospectively analyzed. Score parameters were documented at the time of diagnosis (T0) and 6 h later (T6) to calculate a dynamic score. Survival on day 7 and 56 as well as ICU and hospital mortality were analyzed in regard to the score as well as the delay of hemoadsorption therapy. Results: Of the 502 patients analyzed, 198 received adjunctive CytoSorb treatment and 304 received standard therapy. Septic shock was typically represented by 5 points, while >6 points indicated a situation refractory to standard therapy with the worst outcome in patients shown by >8 points. The differences in mortality between the score groups (<6, 6–8, >8 points) were significant. Analysis further showed a significant 56-day, ICU and hospital survival advantage in CytoSorb patients when therapy was started early. Conclusion: We created a scoring system allowing for the assessment of the clinical development of patients in the early phase of septic shock. Applying this approach, we were able to detect populations with a distinct mortality pattern. The data also showed that an early start of CytoSorb therapy was associated with significantly improved survival. As a next step, this easy-to-apply scoring system would require validation in a prospective manner to learn whether patients to be treated with hemoadsorption therapy in the course of septic shock could thereby be identified.
Roles of Early Mobilization Program in Preventing Muscle Weakness and Decreasing Psychiatric Disorders in Patients with Coronavirus Disease 2019 Pneumonia: A Retrospective Observational Cohort Study
Authors: Kotani Toru , Sugiyama Mizuki , Matsuzaki Fumika , Kubodera Kota , Saito Jin , Kaneki Mika , Shono Atsuko , Maruo Hiroko , Mori Maiko , Ohta Shin , Kasai Fumihito
Published: June 2021

Although many coronavirus 2019 patients have experienced persistent symptoms and a long-term decline in quality of life after discharge, the details of these persistent symptoms and the effect of early rehabilitation are still unclear. We conducted a single-center, retrospective observational study to investigate the prevalence of persistent symptoms three months after discharge from the intensive care unit by checking the medical records. All patients received an early mobilization program. Four out of 13 patients (31%) had postintensive care syndrome. No patients had muscle weakness, and 11 patients (85%) returned to their previous work. However, psychiatric disorder, such as anxiety (23%) and posttraumatic stress disorder (15%), were observed. Eleven patients claimed persistent symptoms, including fatigue and numbness in the extremities. Our results suggest that the implementation of an early rehabilitation program plays some role in preventing muscle weakness and that decreasing psychiatric disorders should be a next target of patient care in the intensive care unit.
Evaluation of Strategies to Fight COVID-19: The French Paradigm
Authors: Giraud-Gatineau Audrey , Gautret Philippe , Colson Philippe , Chaudet Hervé , Raoult Didier
Published: June 2021

(1) Background: We collected COVID-19 mortality data and the age distribution of the deceased in France and other European countries, as well as specifically in the cities of Paris and Marseille, and compared them. (2) Methods: Data on mortality related to COVID-19 and the associated age distribution were collected from government institutions in various European countries. In France, data were obtained from INSEE and Santé Publique France. All-cause mortality was also examined in order to study potential excess mortality using EuroMOMO. The Marseille data came from the epidemiological surveillance system. (3) Results: France is one of the European countries most impacted by COVID-19. Its proportion of deaths in people under 60 years of age is higher (6.5%) than that of Italy (4.6%) or Spain (4.7%). Excess mortality (5% more deaths) was also observed. Ile-de-France and the Grand-Est are the two French regions with the highest mortality. The proportion of deaths in the under-60 age group was considerable in Ile-de-France (9.9% vs. 4.5% in the Southern region). There are significantly higher numbers of patients hospitalized, in intensive care and deceased in Paris than in Marseille. (4) Conclusions: No patient management, i.e., from screening to diagnosis, including biological assessment and clinical examination, likely explains the high mortality associated with COVID-19.
Long-Term Outcomes of Patients with Coronavirus Disease 2019 at One Year after Hospital Discharge
Authors: Maestre-Muñiz Modesto M. , Arias Ángel , Mata-Vázquez Emilia , Martín-Toledano María , López-Larramona Germán , Ruiz-Chicote Ana María , Nieto-Sandoval Bárbara , Lucendo Alfredo J.
Published: June 2021

Background: The long-term effects of COVID-19 remain largely unclear. This study aims to investigate post-acute health consequences and mortality one year after hospital discharge. Methods: All surviving adult patients who were discharged after hospital admission due to acute COVID-19 in the first wave of the pandemic underwent a comprehensive interview. Functional assessment was performed in patients aged over 65. Clinical and hospital records were reviewed and mortality causes assessed. Results: A total of 587 patients with COVID-19 were discharged from hospital, including 266 after hospital admission and 321 from the emergency room. Mortality within the following year occurred in 34/266 (12.8%) and 10/321 (3.1%), respectively, due to causes directly or possibly related to COVID-19 in 20.5% and 25% of patients. Post-COVID-19 syndrome was assessed in 543 patients at one year from discharge. Any clinical complaint was reported by 90.1% of patients who needed hospitalization and 80.4% of those discharged from the emergency room (p = 0.002), with breathlessness (41.6%), tiredness (35.4%), ageusia (30.2%), and anosmia (26.3%) being the most common complaints. Ongoing symptoms attributed to COVID-19 were reported by 66.8% and 49.5% of patients, respectively (p < 0.001). Newly developed COPD, asthma, diabetes, heart failure, and arthritis—as well as worsening of preexisting comorbidities—were found. Conclusions: One-year mortality among survivors of acute COVID-19 was 7.5%. A significant proportion of COVID-19 patients experienced ongoing symptoms at 1 year from onset of the disease.
Steroid-Sparing Effect of Tocilizumab and Methotrexate in Patients with Polymyalgia Rheumatica: A Retrospective Cohort Study
Authors: Izumi Keisuke , Murata Okinori , Higashida-Konishi Misako , Kaneko Yuko , Oshima Hisaji , Takeuchi Tsutomu
Published: June 2021

Polymyalgia rheumatica (PMR) is an inflammatory disorder characterized by pain and stiffness in the shoulders, hips, and proximal limbs; it usually affects elderly patients. The effectiveness of methotrexate and tocilizumab in PMR treatment has not been extensively studied. Thus, we aimed to assess the steroid-sparing effect of tocilizumab and methotrexate in PMR in clinical practice. Consecutive patients with PMR in our hospitals, who were included in our retrospective cohort, were reviewed between 2005 and 2015 and divided into the following groups according to their treatments: prednisolone or none (prednisolone group), methotrexate ± prednisolone (methotrexate group), or tocilizumab ± prednisolone (tocilizumab group). The prednisolone dose at the last follow-up was compared. A total of 227 patients with an average age of 74 years were enrolled. No difference in baseline characteristics was found among the three groups. The prednisolone dose at the last follow-up was lower (0 vs. 3.0 vs. 3.5 mg/day, p < 0.001) and the prednisolone discontinuation rate was higher (80.0% vs. 28.3% vs. 18.8%, p < 0.0001) in the tocilizumab group than in the prednisolone and methotrexate groups. This study suggested that tocilizumab has a steroid-sparing effect in PMR. Tocilizumab can be an option in the management of PMR. Future studies are warranted to confirm our findings.
Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020
Authors: Taieb Fabien , Mbaye Khardiata Diallo , Tall Billo , Lakhe Ndèye Aïssatou , Talla Cheikh , Thioub Daouda , Ndoye Amadou Moustapha , Ka Daye , Gaye Aboubacry , Cissé Diallo Viviane Marie-Pierre , Dia Ndongo , Ba Pape Samba , Cissé Mamadou , Diop Moustapha , Diagne Cheikh Tidiane , Fortes Louise , Diop Mamadou , Fall Ndèye Maguette , Sarr Fatoumata Diène , Diatta Margarite , Barry Mamadou Aliou , Badiane Aboubakar Sidikh , Seck Abdoulaye , Dubrous Philippe , Faye Ousmane , Vigan-Womas Inès , Loucoubar Cheikh , Sall Amadou Alpha , Seydi Moussa
Published: June 2021

As of today, little data is available on COVID-19 in African countries, where the case management relied mainly on a treatment by association between hydroxychloroquine (HCQ) and azithromycin (AZM). This study aimed to understand the main clinical outcomes of COVID-19 hospitalized patients in Senegal from March to October 20202. We described the clinical characteristics of patients and analysed clinical status (alive and discharged versus hospitalized or died) at 15 days after Isolation and Treatment Centres (ITC) admission among adult patients who received HCQ plus AZM and those who did not receive this combination. A total of 926 patients were included in this analysis. Six hundred seventy-four (674) (72.8%) patients received a combination of HCQ and AZM. Results showed that the proportion of patient discharge at D15 was significantly higher for patients receiving HCQ plus AZM (OR: 1.63, IC 95% (1.09–2.43)). Factors associated with a lower proportion of patients discharged alive were: age ≥ 60 years (OR: 0.55, IC 95% (0.36–0.83)), having of at least one pre-existing disorder (OR: 0.61, IC 95% (0.42–0.90)), and a high clinical risk at admission following NEWS score (OR: 0.49, IC 95% (0.28–0.83)). Few side effects were reported including 2 cases of cardiac rhythmic disorders in the HCQ and AZM group versus 13 in without HCQ + AZM. An improvement of clinical status at 15 days was found for patients exposed to HCQ plus AZM combination.
Prognostic Value of Circadian Rhythm of Brain Temperature in Traumatic Brain Injury
Authors: Kuo Lu-Ting , Lu Hsueh-Yi , Huang Abel Po-Hao
Published: June 2021

Hypothermia has been used in postoperative management of traumatic brain injury (TBI); however, the rhythmic variation and prognostic value of brain temperature after TBI have never been studied. This study describes diurnal brain temperature patterns in comatose patients with TBI. Mesors of brain temperature, amplitude, and acrophase were estimated from recorded temperature measurements using cosinor analysis. The association of these patterns with clinical parameters, mortality, and functional outcomes in a 12-month follow-up was examined. According to the cosinor analysis, 59.3% of patients presented with circadian rhythms of brain temperature in the first 72 h postoperatively. The rhythm-adjusted mesor of brain temperature was 37.39 ± 1.21 °C, with a diminished mean amplitude of 0.28 (±0.25) °C; a shift of temperature acrophase was also observed. Multivariate logistic regression analysis revealed that initial Glasgow coma scale score, age, elevated blood glucose level, and circadian rhythm of brain temperature seemed to be predictive and prognostic factors of patients’ functional outcomes. For the prediction of survival status, younger patients or those patients with mesor within the middle 50% of brain temperature were more likely to survive. The analysis of brain temperature rhythms in patients with moderate and severe TBI provided additional predictive information related to mortality and functional outcomes.
Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up
Authors: Santos-García Diego , de Deus Teresa , Cores Carlos , Canfield Hector , Paz González Jose , Martínez Miró Cristina , Valdés Aymerich Lorena , Suárez Ester , Jesús Silvia , Aguilar Miquel , Pastor Pau , Planellas Lluis , Cosgaya Marina , García Caldentey Juan , Caballol Nuria , Legarda Ines , Hernández-Vara Jorge , Cabo Iria , López Manzanares Lydia , González Aramburu Isabel , Ávila Rivera Maria , Catalán Maria , Nogueira Victor , Puente Victor , Dotor Julio , Borrué Carmen , Solano Berta , Álvarez Sauco Maria , Vela Lydia , Escalante Sonia , Cubo Esther , Carrillo Francisco , Martínez Castrillo Juan , Sánchez Alonso Pilar , Alonso Gemma , López Ariztegui Nuria , Gastón Itziar , Kulisevsky Jaime , Blázquez Marta , Seijo Manuel , Rúiz Martínez Javier , Valero Caridad , Kurtis Monica , de Fábregues Oriol , Ardura Jessica , Alonso Ruben , Ordás Carlos , López Díaz Luis , McAfee Darrian , Martinez-Martin Pablo , Mir Pablo ,   COPPADIS Study Group
Published: June 2021

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.
Learning Spatial Design through Interdisciplinary Collaboration
Authors: Bryant Martin
Published: June 2021

Spatial design at interior, site, city and regional scales is increasingly complex, and will continue to be so with the uncertainty of the climate crisis and the growing place-based intricacies of pluralist societies. In response to this complexity, professional design practice has pursued new ways of working. More design projects are becoming more interdisciplinary and less hierarchically structured, involving more collaborative project teams with a variety of backgrounds in architecture, urban design, landscape and interior architecture, engineering, ecological sciences and art. At universities, the design-learning studio which pedagogically champions the authentic replication of design practice projects, has also bifurcated. While teaching design through the traditional disciplinary-based problem-solving processes of an individual project is still understandably commonplace, a new type of studio has emerged, led by group work and interdisciplinary collaborations, and framed by the complexity of a seemingly irreconcilable problematic subject. This emergent domain warrants more research into pedagogical structures, teaching techniques and learning activities; and this paper explains such investigations undertaken through the live educational practice of two interdisciplinary studios in two years, drawing conclusions from student feedback gathered via questionnaires and focus group interviews. The findings suggest that teaching formats in this type of studio need to facilitate a balance between trusting relationships and immersive experiences; and that effective teaching techniques entail the development of more accessible communication techniques in conceptual diagramming and linguistic idiom.
Molecular Components of Nitrogen Fixation Gene Cluster and Associated Enzymatic Activities of Non-Heterocystous Thermophilic Cyanobacterium Thermoleptolyngbya sp.
Authors: Li Meijin , Cheng Lei , Tang Jie , Daroch Maurycy
Published: June 2021

Thermoleptolyngbya is a genus of non-heterocystous cyanobacteria that are typical inhabitants of hot spring microbial mats. These filamentous cyanobacteria are capable of nitrogen fixation. In this study, we examined the genome sequences of five publicly available Thermoleptolyngbya strains to explore their nitrogen fixation gene cluster. Analysis of the nitrogen-fixation clusters in these extremophilic strains revealed that the cluster is located in a single locus in Thermoleptolyngbyace. The average nucleotide and amino acid identities of the nitrogen-fixation cluster combined with phylogenetic reconstructions support that nitrogen fixation genes in Thermoleptolyngbyaceae are closely related to one another but also heterogeneous within the genus. The strains from Asia, and China more specifically, generate a separate clade within the genus. Among these strains Thermoleptolyngbya sp. PKUAC-SCTB121 has been selected for experimental validation of clade’s nitrogen fixation capacity. The acetylene reduction experiments of that strain shown that the strain can reduce acetylene to ethylene, indicating a fully functional nitrogenase. The activity of nitrogenase has been tested using different gas compositions across 72 h and exhibited a two-phase trend, high nitrogenase activity at the beginning of the assay that slowed down in the second phase of the analysis.
A Comprehensive Review on the Utilization of Recycled Waste Fibers in Cement-Based Composites
Authors: Ming Yang , Chen Ping , Li Ling , Gan Guoxing , Pan Gelin
Published: June 2021

Ecological problems such as natural resource depletion and massive quantities of waste for disposal are now guiding progressive civilization towards sustainable construction. The reduction of natural resources and the discarding of debris into open landfills are the two main environmental concerns. As a result, managing these solid wastes is a major challenge worldwide. In comparison to disposal, insufficient landfills, ecological degradation and the economic load on the relevant agencies, recycling and reusing waste materials have a considerable influence. Waste fiber has been studied for use as a cement-based composite (CBC) ingredient. Recycling waste fibers not only makes the cement composite more cost-effective and long-lasting but also helps to reduce pollution. Plastics, carpets and steels are among the various types of waste fibers reviewed in this study for their applications in cement-based materials. The mechanical properties of CBCs with different kinds of recycled-waste fibers were explored, including their compressive, flexural and splitting tensile strength and durability properties. The use of recycled fibers in the construction industry can help to ensure sustainability from environmental, economic and social standpoints. As a result, additional scientific research is needed, as well as guidance for more researchers and experts in the construction sector to examine the unknown sustainability paths. The barriers to the effective implementation of waste fiber recycling techniques in the construction sector were reviewed, and various solutions were proposed to stimulate and ensure their use in CBCs. It was concluded that CBCs containing recycled fibers provide a long-term and cost-effective alternative for dealing with waste materials.