bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Traits, Volatile Organic Compounds, and Expression of Key Flavor Genes in Strawberry Genotypes over Harvest Period
Authors: Leonardou Varvara K. , Doudoumis Evangelos , Tsormpatsidis Evangelos , Vysini Eleni , Papanikolopoulos Theofanis , Papasotiropoulos Vasileios , Lamari Fotini N.
Published: December 2021

Six strawberry genotypes were examined for fruit yield and size, important chemical traits (sugars, phenolics, anthocyanins, ascorbic acid, volatiles) and antioxidant properties (ferric reducing power). In addition, we determined the expression of genes and transcription factors (SAAT, FaNES1, FaFAD1, FaEGS2, FaEOBII and FaMYB10) controlling the main flavor and aroma traits, and finally evaluated the effect of the genotype and harvest time on the examined chemical and genetic factors, as well as their intercorrelations. The commercial varieties ‘Fortuna’, ‘Victory’, ‘Calderon’, ‘Rociera’, and two advanced selections Ber22/6 and Ber23/3 were cultivated under the same conditions at Berryplasma World Ltd. plantations (Varda, Ilia, Region of Western Greece). Strawberries were harvested at three different time points over the main harvest period in Greece, i.e., early March (T1), late March (T2) and late April (T3). ‘Fortuna’ exhibited the highest early and total yield, while ‘Calderon’, the highest average berry weight. General Linear Model repeated measures ANOVA demonstrated that the interaction of the genotype and harvest time was significant (p < 0.001) on all tested quality attributes and gene expression levels, showing that each genotype behaves differently throughout the harvest period. Exceptions were observed for: (a) the volatile anhydrides, fatty acids, aromatics and phenylpropanoids (all were greatly affected by the harvest time), and (b) lactones, furaneol and FaEGS2 that were affected only by the genotype. We observed significant intercorrelations among those factors, e.g., the positive correlation of FaFAD1 expression with decalactone and nerolidol, of SAAT with furaneol, trans-cinnamic acid and phenylpropanoids, and of FaEGS2 with decalactone and FaFAD1. Moreover, a strong positive correlation between SAAT and FaMYB10 and a moderate negative one between SAAT and glucose were also detected. Those correlations can be further investigated to reveal potential markers for strawberry breeding. Overall, our study contributes to a better understanding of strawberry physiology, which would facilitate breeding efforts for the development of new strawberry varieties with superior qualitative traits.
Genome-Wide Analysis of the Soybean Calmodulin-Binding Protein 60 Family and Identification of GmCBP60A-1 Responses to Drought and Salt Stresses
Authors: Yu Qian , Liu Ya-Li , Sun Guo-Zhong , Liu Yuan-Xia , Chen Jun , Zhou Yong-Bin , Chen Ming , Ma You-Zhi , Xu Zhao-Shi , Lan Jin-Hao
Published: December 2021

Calmodulin-binding protein 60 (CBP60) members constitute a plant-specific protein family that plays an important role in plant growth and development. In the soybean genome, nineteen CBP60 members were identified and analyzed for their corresponding sequences and structures to explore their functions. Among GmCBP60A-1, which primarily locates in the cytomembrane, was significantly induced by drought and salt stresses. The overexpression of GmCBP60A-1 enhanced drought and salt tolerance in Arabidopsis, which showed better state in the germination of seeds and the root growth of seedlings. In the soybean hairy roots experiment, the overexpression of GmCBP60A-1 increased proline content, lowered water loss rate and malondialdehyde (MDA) content, all of which likely enhanced the drought and salt tolerance of soybean seedlings. Under stress conditions, drought and salt response-related genes showed significant differences in expression in hairy root soybean plants of GmCBP60A-1-overexpressing and hairy root soybean plants of RNAi. The present study identified GmCBP60A-1 as an important gene in response to salt and drought stresses based on the functional analysis of this gene and its potential underlying mechanisms in soybean stress-tolerance.
Ezrin Regulates Ca2+ Ionophore-Induced Plasma Membrane Translocation of Aquaporin-5
Authors: Muroi Shin-ichi , Isohama Yoichiro
Published: December 2021

Aquaporin-5 (AQP5) is selectively expressed in the apical membrane of exocrine glands, such as salivary, sweat, and submucosal airway glands, and plays important roles in maintaining their secretory functions. Because AQP5 is not regulated by gating, localization on the plasma membrane is important for its water-permeable function. Ezrin is an ezrin–radixin–moesin family protein that serves as a crosslinker between the plasma membrane and actin cytoskeleton network. It plays important roles in translocation of various membrane proteins to mediate vesicle trafficking to the plasma membrane. In this study, we examined the effects of ezrin inhibition on membrane trafficking of AQP5. Ezrin inhibition selectively suppressed an ionomycin-induced increase in AQP5 translocation to the plasma membrane of mouse lung epithelial cells (MLE-12) without affecting the steady-state level of plasma membrane AQP5. Taken together, our data suggest that AQP5 translocates to the plasma membrane through at least two pathways and that ezrin is selectively involved in a stimulation-dependent pathway.
Intra-Individual Variability of Human Dental Pulp Stem Cell Features Isolated from the Same Donor
Authors: Pilbauerova Nela , Schmidt Jan , Soukup Tomas , Duska Jan , Suchanek Jakub
Published: December 2021

It is primarily important to define the standard features and factors that affect dental pulp stem cells (DPSCs) for their broader use in tissue engineering. This study aimed to verify whether DPSCs isolated from various teeth extracted from the same donor exhibit intra-individual variability and what the consequences are for their differentiation potential. The heterogeneity determination was based on studying the proliferative capacity, viability, expression of phenotypic markers, and relative length of telomere chromosomes. The study included 14 teeth (6 molars and 8 premolars) from six different individuals ages 12 to 16. We did not observe any significant intra-individual variability in DPSC size, proliferation rate, viability, or relative telomere length change within lineages isolated from different teeth but the same donor. The minor non-significant variances in phenotype were probably mainly because DPSC cell lines comprised heterogeneous groups of undifferentiated cells independent of the donor. The other variances were seen in DPSC lineages isolated from the same donor, but the teeth were in different stages of root development. We also did not observe any changes in the ability of cells to differentiate into mature cell lines—chondrocytes, osteocytes, and adipocytes. This study is the first to analyze the heterogeneity of DPSC dependent on a donor.
Cyclodextrin-Containing Hydrogels: A Review of Preparation Method, Drug Delivery, and Degradation Behavior
Authors: Liu Jiayue , Tian Bingren , Liu Yumei , Wan Jian-Bo
Published: December 2021

Hydrogels possess porous structures, which are widely applied in the field of materials and biomedicine. As a natural oligosaccharide, cyclodextrin (CD) has shown remarkable application prospects in the synthesis and utilization of hydrogels. CD can be incorporated into hydrogels to form chemically or physically cross-linked networks. Furthermore, the unique cavity structure of CD makes it an ideal vehicle for the delivery of active ingredients into target tissues. This review describes useful methods to prepare CD-containing hydrogels. In addition, the potential biomedical applications of CD-containing hydrogels are reviewed. The release and degradation process of CD-containing hydrogels under different conditions are discussed. Finally, the current challenges and future research directions on CD-containing hydrogels are presented.
Influence of Electroconvection on Chronopotentiograms of an Anion-Exchange Membrane in Solutions of Weak Polybasic Acid Salts
Authors: Pismenskaya Natalia , Rybalkina Olesya , Moroz Ilya , Mareev Semen , Nikonenko Victor
Published: December 2021

Visualization of electroconvective (EC) vortices at the undulated surface of an AMX anion-exchange membrane (Astom, Osaka, Japan) was carried out in parallel with the measurement of chronopotentiograms. Weak polybasic acid salts, including 0.02 M solutions of tartaric (NaHT), phosphoric (NaH2PO4), and citric (NaH2Cit) acids salts, and NaCl were investigated. It was shown that, for a given current density normalized to the theoretical limiting current calculated by the Leveque equation (i/ilimtheor), EC vortex zone thickness, dEC, decreases in the order NaCl > NaHT > NaH2PO4 > NaH2Cit. This order is inverse to the increase in the intensity of proton generation in the membrane systems under study. The higher the intensity of proton generation, the lower the electroconvection. This is due to the fact that protons released into the depleted solution reduce the space charge density, which is the driver of EC. In all studied systems, a region in chronopotentiograms between the rapid growth of the potential drop and the attainment of its stationary values corresponds to the appearance of EC vortex clusters. The amplitude of the potential drop oscillations in the chronopotentiograms is proportional to the size of the observed vortex clusters.
Generation of a Retargeted Oncolytic Herpes Virus Encoding Adenosine Deaminase for Tumor Adenosine Clearance
Authors: Gentile Chiara , Finizio Arianna , Froechlich Guendalina , D’Alise Anna Morena , Cotugno Gabriella , Amiranda Sara , Nicosia Alfredo , Scarselli Elisa , Zambrano Nicola , Sasso Emanuele
Published: December 2021

Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine. Methods: Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP). Results: Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function. Conclusions: Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation.
The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions
Authors: Chishti Arif Ali , Baumstark-Khan Christa , Nisar Hasan , Hu Yueyuan , Konda Bikash , Henschenmacher Bernd , Spitta Luis F. , Schmitz Claudia , Feles Sebastian , Hellweg Christine E.
Published: December 2021

Nuclear factor κB (NF-κB) activation might be central to heavy ion-induced detrimental processes such as cancer promotion and progression and sustained inflammatory responses. A sensitive detection system is crucial to better understand its involvement in these processes. Therefore, a DD-tdTomato fluorescent protein-based reporter system was previously constructed with human embryonic kidney (HEK) cells expressing DD-tdTomato as a reporter under the control of a promoter containing NF-κB binding sites (HEK-pNFκB-DD-tdTomato-C8). Using this reporter cell line, NF-κB activation after exposure to different energetic heavy ions (16O, 95 MeV/n, linear energy transfer—LET 51 keV/µm; 12C, 95 MeV/n, LET 73 keV/μm; 36Ar, 95 MeV/n, LET 272 keV/µm) was quantified considering the dose and number of heavy ions hits per cell nucleus that double NF-κB-dependent DD-tdTomato expression. Approximately 44 hits of 16O ions and ≈45 hits of 12C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas only ≈3 hits of 36Ar ions were sufficient. In the presence of Shield-1, a synthetic molecule that stabilizes DD-tdTomato, even a single particle hit of 36Ar ions doubled NF-κB-dependent DD-tdTomato expression. In conclusion, stabilization of the reporter protein can increase the sensitivity for NF-κB activation detection by a factor of three, allowing the detection of single particle hits’ effects.
Unprecedented Density and Persistence of Feral Honey Bees in Urban Environments of a Large SE-European City (Belgrade, Serbia)
Authors: Bila Dubaić Jovana , Simonović Slađan , Plećaš Milan , Stanisavljević Ljubiša , Davidović Slobodan , Tanasković Marija , Ćetković Aleksandar
Published: December 2021

It is assumed that wild honey bees have become largely extinct across Europe since the 1980s, following the introduction of exotic ectoparasitic mite (Varroa) and the associated spillover of various pathogens. However, several recent studies reported on unmanaged colonies that survived the Varroa mite infestation. Herewith, we present another case of unmanaged, free-living population of honey bees in SE Europe, a rare case of feral bees inhabiting a large and highly populated urban area: Belgrade, the capital of Serbia. We compiled a massive data-set derived from opportunistic citizen science (>1300 records) during the 2011–2017 period and investigated whether these honey bee colonies and the high incidence of swarms could be a result of a stable, self-sustaining feral population (i.e., not of regular inflow of swarms escaping from local managed apiaries), and discussed various explanations for its existence. We also present the possibilities and challenges associated with the detection and effective monitoring of feral/wild honey bees in urban settings, and the role of citizen science in such endeavors. Our results will underpin ongoing initiatives to better understand and support naturally selected resistance mechanisms against the Varroa mite, which should contribute to alleviating current threats and risks to global apiculture and food production security.
The Active Isoforms of MGP Are Expressed in Healthy and Varicose Veins without Calcification
Authors: Gheorghe Simona R. , Vermeer Cees , Olteanu Gabriel , Silaghi Ciprian N. , Crăciun Alexandra M.
Published: December 2021

Matrix Gla protein (MGP), a local inhibitor of tissue mineralization, is associated with vascular calcification. Depending on the carboxylation and phosphorylation status, MGP has active conformations, e.g., carboxylated MGP (cMGP) and phosphorylated MGP (pMGP), but also inactive conformations, e.g., uncarboxylated MGP (ucMGP) and dephosphorylated MGP (dpMGP). Our purpose was to assess the presence of all MGP conformations in healthy veins (HV) and varicose veins (VV), concurrently with the analysis of circulating total MGP (tMGP) before and after the surgical stripping of VV. We collected samples from the great saphenous vein, considered as control group, and tissue from VV, designated as VV group. Plasma levels of tMGP were significantly decreased after the surgical removal of the VV (before 59.5 ± 17.2 vs. after 38.1 ± 11.3, p < 0.001). By using immunohistochemistry staining, we identified local cMGP and pMGP in the control and VV groups, both without calcification, while ucMGP and dpMGP were absent. cMGP was observed in the nucleus and cytoplasm and pMGP in the nucleus of cells belonging to the tunica media, tunica intima and vasa vasorum. Therefore, the active conformations of MGP (cMGP and pMGP) are prevalent in HV and VV without calcification, affirming their anti-calcifying role in veins.
Real-World Long-Term Clinical Outcomes of Ultrathin Strut Biodegradable Polymer Drug-Eluting Stents in Korean ST-Segment-Elevation Myocardial Infarction (STEMI) Patients with or without Acute Heart Failure Undergoing Primary Percutaneous Coronary Intervention
Authors: Jang Albert Youngwoo , Yu Jongwook , Oh Pyung Chun , Kim Minsu , Suh Soon Yong , Lee Kyounghoon , Han Seung Hwan , Kang Woong Chol
Published: December 2021

Biodegradable polymers (BDPs) and ultrathin struts were recently introduced to drug-eluting stents (DES) to further improve outcomes. In this study, we analyzed and compared the effect of the ultrathin strut BDP-DES (UBDP-DES) with the conventional durable polymer-DES (DP-DES) in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI). A total of 356 STEMI patients (n = 160 in the UBDP-DES group and n = 196 in the DP-DES group) were enrolled. The primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction, and ischemic-driven, target lesion revascularization (ID-TLR). The mean age was 60.3 ± 12.7 years (male 81.7%), and the median follow-up duration was 63.8 months. TLF was numerically more frequent in the UBDP-DES group (8.1% vs. 4.1%; HR 2.14; 95% CI 0.89–5.18; p = 0.091). Propensity score matching (PSM) was performed to balance discrepancies in the baseline characteristics due to patients in the UBDP-DES group initially having more unstable vital signs. However, after PSM (n = 116 in each group), there was no significant difference in TLF (5.3% vs. 5.3%; HR 1.04, 95% CI 0.34-3.22; p = 0.947) or other secondary endpoints including ID-TLR. In the subgroup analysis, subjects with initial acute heart failure (AHF), defined as Killip class ≥ 3, were associated with 13.6% chance of 30-day mortality (9-fold of those without AHF), although chances of repeat revascularization were low (3.0%). Among patients with AHF, the UBDP-DES group was associated with a numerically higher chance of TLF compared with the DP-DES group. There was no difference in TLF between groups in patients without AHF. This study showed that UBDP-DES has long-term clinical outcomes similar to those of conventional DP-DES in real-world Korean STEMI patients receiving PPCI, especially in those without initial AHF.
Revisiting One-Stage Urethroplasties for Distal Urethral Strictures
Authors: Hofer Matthias D. , Cooley Lauren Folgosa , Elmasri Ayman , Martins Francisco E.
Published: December 2021

Background: Reconstructive approaches for distal urethral strictures range from simple meatotomy to utilizing grafts or flaps depending on the etiology, length and location. We describe a contemporary cohort of distal urethral strictures and report a surgical technique termed distal one-stage urethroplasty developed to address the majority of distal urethral strictures encountered. Methods: Thirty-four patients were included. The mean age was 56.7 years (range 15.7–84.9 years), the mean stricture length was 1.1 cm (0.5–1.5) and the mean follow-up was 42.5 months (28–61.3). Results: The vast majority of distal strictures (27/34 (79.4%)) were treated with our hybrid one-stage approach combining a distal urethral reconstruction with excision of the scar tissue without the need to use grafts or flaps. The average stricture length was 0.68 cm and average operative time was 24.43 min. Post-operative spraying was reported in a minority of patients (4/27 (14.8%)). The length of stricture and surgery were significantly longer in those 7/34 (20.6%) patients in whom grafts or flaps were used (2.88 cm and 154.8 min, respectively, p < 0.001 for both when compared to the hybrid one-stage approach). We noted 6/34 (17.6%) recurrences of distal urethral strictures, all of which were treated successfully with graft and flap repairs. Conclusions: The vast majority of distal urethral strictures are amenable to a distal one-stage urethroplasty, avoiding the use of grafts and/or flaps while achieving reasonable outcomes. This limited approach, at least initially, is associated with shorter operative time and time of catheter placement and avoids morbidity associated with graft or flap harvesting. Spraying of urine is seldomly encountered and comparable to other approaches addressing distal urethral strictures.
Special Issue: Rare Respiratory Diseases: A Personal and Public Health Issue
Authors: Magallón María , Bañuls Lucía , Castillo Silvia , Navarro-García María Mercedes , González Cruz , Dasí Francisco
Published: December 2021

In the 1970s, the term “rare disease” was coined to describe a category of inherited metabolic diseases with low prevalence and a wide range of symptoms [...]
COVID-19 as a Catalyst for Same-Day Discharge Total Shoulder Arthroplasty
Authors: Menendez Mariano E. , Keegan Noah , Werner Brian C. , Denard Patrick J.
Published: December 2021

The COVID-19 pandemic caused major disruptions to the healthcare system, but its impact on the transition to same-day discharge shoulder arthroplasty remains unexplored. This study assessed the effect of COVID-19 on length of stay (LOS), same-day discharge rates, and other markers of resource use after elective total shoulder arthroplasty. A total of 508 consecutive patients undergoing elective primary total shoulder arthroplasty between 2019 and 2021 were identified and divided into 2 cohorts: “pre-COVID” (March 2019–March 2020; n = 263) and “post-COVID” (May 2020–March 2021; n = 245). No elective shoulder arthroplasties were performed at our practice between 18 March and 11 May 2020. Outcome measures included LOS, same-day discharge, discharge location, and 90-day emergency department (ED) visits, readmissions and reoperations. There were no significant differences in baseline preoperative patient characteristics. Shoulder arthroplasty performed post-COVID was associated with a shorter LOS (12 vs. 16 h, p = 0.017) and a higher rate of same-day discharge (87.3 vs. 79.1%, p = 0.013). The rate of discharge to skilled nursing facilities was similarly low between the groups (1.9 vs. 2.0%, p = 0.915). There was a significant reduction in the rate of 90-day ED visits post-COVID (7.4 vs. 13.3%, p = 0.029), while there were no differences in 90-day reoperation (2.0 vs. 1.5%, p = 0.745) or readmission rates (1.2 vs. 1.9%, p = 0.724). The COVID-19 pandemic seems to have accelerated the shift towards shorter stays and more same-day discharge shoulder arthroplasties, while reducing unexpected acute health needs (e.g., ED visits) without adversely affecting readmission and reoperation rates.
A Systematic Review of Persistent Symptoms and Residual Abnormal Functioning following Acute COVID-19: Ongoing Symptomatic Phase vs. Post-COVID-19 Syndrome
Authors: Jennings Glenn , Monaghan Ann , Xue Feng , Mockler David , Romero-Ortuño Román
Published: December 2021

Objective: To compare the two phases of long COVID, namely ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life. Design: Systematic review. Data Sources: Electronic search of EMBASE, MEDLINE, ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar between January and April 2021, and manual search for relevant citations from review articles. Eligibility Criteria: Cross-sectional studies, cohort studies, randomised control trials, and case-control studies with participant data concerning long COVID symptomatology or abnormal functioning. Data Extraction: Studies were screened and assessed for risk of bias by two independent reviewers, with conflicts resolved with a third reviewer. The AXIS tool was utilised to appraise the quality of the evidence. Data were extracted and collated using a data extraction tool in Microsoft Excel. Results: Of the 1145 studies screened, 39 were included, all describing adult cohorts with long COVID and sample sizes ranging from 32 to 1733. Studies included data pertaining to symptomatology, pulmonary functioning, chest imaging, cognitive functioning, psychological disorder, and/or quality of life. Fatigue presented as the most prevalent symptom during both OSC and PCS at 43% and 44%, respectively. Sleep disorder (36%; 33%), dyspnoea (31%; 40%), and cough (26%; 22%) followed in prevalence. Abnormal spirometry (FEV1 < 80% predicted) was observed in 15% and 11%, and abnormal chest imaging was observed in 34% and 28%, respectively. Cognitive impairments were also evident (20%; 15%), as well as anxiety (28%; 34%) and depression (25%; 32%). Decreased quality of life was reported by 40% in those with OSC and 57% with PCS. Conclusions: The prevalence of OSC and PCS were highly variable. Reported symptoms covered a wide range of body systems, with a general overlap in frequencies between the two phases. However, abnormalities in lung function and imaging seemed to be more common in OSC, whilst anxiety, depression, and poor quality of life seemed more frequent in PCS. In general, the quality of the evidence was moderate and further research is needed to understand longitudinal symptomatology trajectories in long COVID. Systematic Review Registration: Registered with PROSPERO with ID #CRD42021247846.
Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine
Authors: Silvestro Marcello , Tessitore Alessandro , Orologio Ilaria , Sozio Pasquale , Napolitano Giuseppe , Siciliano Mattia , Tedeschi Gioacchino , Russo Antonio
Published: December 2021

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iβ interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care.
Combined Transfibular and Anterior Approaches Increase Union Rate and Decrease Non-Weight-Bearing Periods in Ankle Arthrodesis: Combined Approaches in Ankle Arthrodesis
Authors: Park Jeong-Jin , Son Whee-Sung , Woo In-Ha , Park Chul-Hyun
Published: December 2021

The transfibular approach is a widely used method in ankle arthrodesis. However, it is difficult to correct coronal plane deformity. Moreover, it carries a risk of nonunion and requires long periods of non-weight-bearing because of its relatively weak stability. We hypothesized that the transfibular approach combined with the anterior approach in ankle arthrodesis wound yield a higher fusion rate and shorter non-weight-bearing period. This study was performed to evaluate the clinical and radiographic results and postoperative complications in ankle arthrodesis using combined transfibular and anterior approaches in end-stage ankle arthritis. Thirty-five patients (36 ankles) with end-stage ankle arthritis were consecutively treated using ankle arthrodesis by combined transfibular and anterior approaches. The subjects were 15 men and 20 women, with a mean age of 66.5 years (46–87). Clinical results were assessed using the visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society (AOFAS) scores, and the ankle osteoarthritis scale (AOS) preoperatively and at the last follow-up. Radiographic results were assessed with various radiographic parameters on ankle weight-bearing radiographs and hindfoot alignment radiographs. All clinical scores significantly improved after surgery. Union was obtained in all cases without additional surgery. Talus center migration (p = 0.001), sagittal talar migration (p < 0.001), and hindfoot alignment angle (p = 0.001) significantly improved after surgery. One partial skin necrosis, two screw penetrations of the talonavicular joint, and four anterior impingements because of the bulky anterior plate occurred after surgery. In conclusion, combined transfibular and anterior approaches could be a good method to increase the union rate and decrease the non-weight-bearing periods in ankle arthrodesis.
Predictive Model for High Coronary Artery Calcium Score in Young Patients with Non-Dialysis Chronic Kidney Disease
Authors: Oh Tae Ryom , Song Su Hyun , Choi Hong Sang , Suh Sang Heon , Kim Chang Seong , Jung Ji Yong , Choi Kyu Hun , Oh Kook-Hwan , Ma Seong Kwon , Bae Eun Hui , Kim Soo Wan
Published: December 2021

Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model’s performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies.
The Influence of Baseline Clinical Status and Surgical Strategy on Early Good to Excellent Result in Spinal Lumbar Arthrodesis: A Machine Learning Approach
Authors: Berjano Pedro , Langella Francesco , Ventriglia Luca , Compagnone Domenico , Barletta Paolo , Huber David , Mangili Francesca , Licandro Ginevra , Galbusera Fabio , Cina Andrea , Bassani Tito , Lamartina Claudio , Scaramuzzo Laura , Bassani Roberto , Brayda-Bruno Marco , Villafañe Jorge Hugo , Monti Lorenzo , Azzimonti Laura
Published: December 2021

The study aims to create a preoperative model from baseline demographic and health-related quality of life scores (HRQOL) to predict a good to excellent early clinical outcome using a machine learning (ML) approach. A single spine surgery center retrospective review of prospectively collected data from January 2016 to December 2020 from the institutional registry (SpineREG) was performed. The inclusion criteria were age ≥ 18 years, both sexes, lumbar arthrodesis procedure, a complete follow up assessment (Oswestry Disability Index—ODI, SF-36 and COMI back) and the capability to read and understand the Italian language. A delta of improvement of the ODI higher than 12.7/100 was considered a “good early outcome”. A combined target model of ODI (Δ ≥ 12.7/100), SF-36 PCS (Δ ≥ 6/100) and COMI back (Δ ≥ 2.2/10) was considered an “excellent early outcome”. The performance of the ML models was evaluated in terms of sensitivity, i.e., True Positive Rate (TPR), specificity, i.e., True Negative Rate (TNR), accuracy and area under the receiver operating characteristic curve (AUC ROC). A total of 1243 patients were included in this study. The model for predicting ODI at 6 months’ follow up showed a good balance between sensitivity (74.3%) and specificity (79.4%), while providing a good accuracy (75.8%) with ROC AUC = 0.842. The combined target model showed a sensitivity of 74.2% and specificity of 71.8%, with an accuracy of 72.8%, and an ROC AUC = 0.808. The results of our study suggest that a machine learning approach showed high performance in predicting early good to excellent clinical results.
Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome
Authors: Daradics Zsofia , Crecan Cristian M. , Rus Mirela A. , Morar Iancu A. , Mircean Mircea V. , Cătoi Adriana Florinela , Cecan Andra Diana , Cătoi Cornel
Published: December 2021

Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70–80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) and has insulin dysregulation as a central and consistent feature. It is often associated with obesity, although EMS may occur in a lean phenotype as well. Other inconsistent features of EMS are cardiovascular changes and adipose dysregulation. Laminitis is the main clinical consequence of EMS. MetS holds a 30-years old lead in research and represents a clustering of risk factors that comprise abdominal obesity, dyslipidemia, hypertension, and hyperglycemia (impaired fasting glucose or type 2 diabetes mellitus—T2DM), which are associated with doubled atherosclerotic cardiovascular disease risk, and a 5-fold increased risk for T2DM. The main aim of this review is to provide critical information for better understanding of the underlying mechanisms of obesity-related metabolic dysfunction in animals, especially in cows and horses, in comparison with MetS. Human medicine studies can offer suitable candidate mechanisms to fill the existing gap in the literature, which might be indispensable for owners to tackle FCS, EMS, and their consequences.
Glycoprotein Profile Measured by a 1H-Nuclear Magnetic Resonance Based on Approach in Patients with Diabetes: A New Robust Method to Assess Inflammation
Authors: Amigó Núria , Fuertes-Martín Rocío , Malo Ana Irene , Plana Núria , Ibarretxe Daiana , Girona Josefa , Correig Xavier , Masana Lluís
Published: December 2021

Patients with type 2 diabetes mellitus (T2DM) and atherogenic dyslipidemia (AD) are at higher risk of developing cardiovascular diseases (CVDs), so an interest in discovering inflammation biomarkers as indicators of processes related to CVD progression is increasing. This study aims (a) to characterize the plasma glycoprotein profile of a cohort of 504 participants, including patients with and without T2DM and/or AD and controls, and (b) to study the associations between the glycoprotein profile and other lipid and clinical variables in these populations. We characterized the plasma glycoprotein profiles by using 1H-NMR. We quantified the two peaks associated with the concentration of plasma glycoproteins (GlycA and GlycB) and their height/width ratios (H/W GlycA and H/W GlycB), as higher and narrower signals have been related to inflammation. We also quantified GlycF, the signal of which is proportional to the concentration of the acetyl groups of free N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic in the samples. The lipoprotein profile was also determined (Liposcale®). Standard clinical and anthropometric measurements were taken. Multivariate classification models were developed to study the differences between the study groups. Reduced HDL-C levels, increased small dense LDL and HDL particles, and elevated TG levels were significantly associated with glycoprotein variables. Glycoprotein values in the diagnostic groups were significantly different from those in the CT groups. AD and DM conditions together contribute to a positive and significant synergetic effect on the GlycA area (<0.05) and the H/W ratios of GlycA (<0.01) and GlycB (<0.05). By adding the new glycoprotein variables to the traditionally used marker of inflammation C-reactive protein (CRP), the AUC increased sharply for classification models between the CT group and the rest (0.68 to 0.84), patients with and without dyslipidemia (0.54 to 0.86), and between patients with and without diabetes (0.55 to 0.75). 1H-NMR-derived glycoproteins can be used as possible markers of the degree of inflammation associated with T2DM and AD.
Comparison of Efficacy among Three Dermal Substitutes in the Management of Critical Lower-Limb Wounds: The Largest Biases-Reduced Single-Center Retrospective Cohort Study in Literature
Authors: Cottone Giuseppe , Amendola Francesco , Strada Carlo , Bagnato Maria Chiara , Brambilla Roberto , De Francesco Francesco , Vaienti Luca
Published: December 2021

Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon’s armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our study aims to retrospectively compare three renowned and extremely similar DS in the management of critical lower limb wounds in the largest cohort analysis currently present in literature. Materials and Methods: We followed a strict protocol of application and evaluation of the DS for each patient and wound and, after a meticulous bias reduction process, we compared final outcomes in terms of efficacy and speed in achieving the defect coverage. Results: Among patients who did not receive a skin graft after the DS, we registered a wound healed surface of 50% for Pelnac, 52% for Integra, and 19% for Nevelia, after 30 days from the external silicon layer removal; among those who received a skin graft after the DS, we observed a significantly lower mean percentage of graft take after 7 days with Pelnac (53%) compared to Integra and Nevelia (92% and 80%, respectively). The overall percentage of wound healed surface obtained after 30 days from the external silicon sheet removal, either with or without skin graft, was 71% for Pelnac, 63% for Integra and 63% for Nevelia. We also ran a sub-group analysis only including grafted wounds with a negative microbiological test and the mean percentage of graft take was similar this time. Eventually, we assessed the influence of the wound’s “chronicity” on its healing, comparing the mean graft take only in “acute” wounds who received a skin graft and it resulted 63% for Pelnac, 91% for Integra and 75% for Nevelia. Conclusions: Integra demonstrates the highest rate of skin graft viability and the highest rate of skin graft takes after 7 days. Pelnac shows the quickest induction of secondary healing in acute wounds. Nevelia is not different from Integra and shows a superior graft take compared to Pelnac, but features the lowest secondary healing induction rate. No differences exist between the three DSs in terms of wound healing after 30 days from the skin graft or from the removal of the external silicon layer.
The Mechanism of Metal Homeostasis in Plants: A New View on the Synergistic Regulation Pathway of Membrane Proteins, Lipids and Metal Ions
Authors: Wu Danxia , Saleem Muhammad , He Tengbing , He Guandi
Published: December 2021

Heavy metal stress (HMS) is one of the most destructive abiotic stresses which seriously affects the growth and development of plants. Recent studies have shown significant progress in understanding the molecular mechanisms underlying plant tolerance to HMS. In general, three core signals are involved in plants’ responses to HMS; these are mitogen-activated protein kinase (MAPK), calcium, and hormonal (abscisic acid) signals. In addition to these signal components, other regulatory factors, such as microRNAs and membrane proteins, also play an important role in regulating HMS responses in plants. Membrane proteins interact with the highly complex and heterogeneous lipids in the plant cell environment. The function of membrane proteins is affected by the interactions between lipids and lipid-membrane proteins. Our review findings also indicate the possibility of membrane protein-lipid-metal ion interactions in regulating metal homeostasis in plant cells. In this review, we investigated the role of membrane proteins with specific substrate recognition in regulating cell metal homeostasis. The understanding of the possible interaction networks and upstream and downstream pathways is developed. In addition, possible interactions between membrane proteins, metal ions, and lipids are discussed to provide new ideas for studying metal homeostasis in plant cells.
Mechanochemical-Assisted Extraction and Hepatoprotective Activity Research of Flavonoids from Sea Buckthorn (Hippophaë rhamnoides L.) Pomaces
Authors: Guo Zili , Cheng Jingya , Zheng Lei , Xu Wenhao , Xie Yuanyuan
Published: December 2021

Pomaces of sea buckthorn berry were usually side-products during the processing of juice. Due to a lack of an economical and effective extraction method, it was typically recognized as waste. For the purpose of resource utilization, the mechanochemical-assisted extraction (MCAE) method was applied to develop an ecofriendly extraction method and product with better pharmacology activity. The parameters were investigated through response surface methodology (RSM) design experiments. The processing conditions were optimized as follows: amount of Na2CO3 40%, ball-to-material rate 29:1 g/g, milling speed 410 rpm, milling time 24 min, extraction temperature 25 °C, extraction time 20 min and the solid-to-solution ratio 1:10 g/mL. Under these conditions, the yields of flavonoids from sea buckthorn pomaces were 26.82 ± 0.53 mg/g, which corresponds to an increase of 2 times in comparison with that extracted by the heat reflux extraction method. Meanwhile, the hepatoprotective activity of sea buckthorn pomaces extracts was studied by the liver injury induced by ip injection of tetracycline. Biochemical and histopathological studies showed that biomarkers in serum and liver of nonalcoholic fatty liver disease (NAFLD) mice were significantly ameliorated when sea buckthorn flavonoids extracted by MCAE were used. Altogether, these results demonstrate that, as a green and efficient extraction, MCAE treatment could increase the extraction yield of sea buckthorn flavonoids, meanwhile it could exhibit significant activity of improving liver function. This research provided a new way to use pomaces of sea buckthorn as a functional food. It also has great value on the comprehensive utilization of nature’s resources.
The Influence of Time and Storage Conditions on the Antioxidant Potential and Total Phenolic Content in Homemade Grape Vinegars
Authors: Antoniewicz Justyna , Kochman Joanna , Jakubczyk Karolina , Janda-Milczarek Katarzyna
Published: December 2021

Fermented foods have been an integral part of the cuisines of almost all cultures in the world. In recent years, they have gained ground again, mainly due to their potential health benefits. One such product is grape vinegar, which apart from characteristic taste, is also a source of compounds with antioxidant activity. The aim of the study was to determine the changes in the antioxidant potential and the content of polyphenols that occur during the storage of grape vinegar obtained by spontaneous fermentation. The research material consisted of vinegar made from different white grape varieties grown in Poland. For each variety, two variants were prepared: with and without the addition of sugar in the fermentation process. The antioxidant potential, polyphenol content, soluble solids content and pH were monitored both during the two-month fermentation process and the subsequent 6-months storage under various conditions. Storage conditions and time of the storage affected the antioxidant activity and polyphenol content. The content of these compounds was also influenced by the variety of grapes used as well as the method of vinegar preparation.
Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VII): Active Principles from Thuja occidentalis L.
Authors: Nakano Daisuke , Ishitsuka Kenji , Ishihara Madoka , Tsuchihashi Ryota , Okawa Masafumi , Tamura Kazuo , Kinjo Junei
Published: December 2021

During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, we identified that the extracts of Thuja occidentalis (Cupressaceae) showed potent anti-proliferative activity in MT-1 and MT-2 cells. Therefore, we attempted to isolate the active components from this plant. We isolated and identified 32 compounds (1–32; eight lignans, 18 terpenoids, and six flavonoids) from the extracts of the leaves and cones. Their structures were determined by spectroscopic analysis. Several of the isolated compounds inhibited the growth of both cell lines. Lignans showed more potent activity than other classes of compounds. A comparison of the activities of compounds 1–8 revealed that the presence of a trans-lactone (linkage of C-6 to C-7) correlated with increased activity. Diterpenes showed moderate activity, and the presence of a ketone moiety at the C-7 position correlated with increased activity in compounds 12–21. In addition, biflavones showed moderate activity, and the presence of methoxy functions appeared to influence the activity of these compounds. Several lignans were lead compound of anti-cancer reagent (etoposide). In conclusion, not only lignans, but also diterpenes and/or biflavones, may be promising candidates for the treatment of adult T-cell leukemia/lymphoma.