bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperammonemia in Russia Due to Carbonic Anhydrase VA Deficiency Caused by Homozygous Mutation p.Lys185Lys (c.555G>A) of the CA5A Gene
Authors: Semenova Natalia , Marakhonov Andrey , Ampleeva Maria , Kurkina Marina , Baydakova Galina , Skoblov Mikhail , Taran Natalia , Babak Olga , Shchukina Ekaterina , Strokova Tatyana
Published: November 2022

Hyperammonemia due to carbonic anhydrase VA deficiency (OMIM# 615751) is a rare, life-threatening hereditary disease caused by biallelic mutations in the CA5A gene, presenting as encephalopathic hyperammonemia of unexplained origin during the neonatal period and infancy. Here, we present a detailed description of a 5-year-old patient with the homozygous mutation p.Lys185Lys (c.555G>A) in the CA5A gene. This variant was previously described by van Karnebeek et al. in 2014 in a boy of Russian origin. We found a high frequency of carriers of this mutation in Russia; 1:213, which is 7 times higher than the expected frequency calculated based on data on Western European populations. Thus, targeted testing for the mutation p.Lys185Lys (c.555G>A) in the CA5A gene should be useful for early detection by selective screening in neonatal intensive care units.
Heterologous Expression of Extracellular Proteinase pAsPs of Aspergillus pseudotamarii in Komagataella phaffii
Authors: Zadorozhny Andrey Valentinovich , Voskoboev Mikhail Evgenyevich , Bochkov Denis Vladimirovich , Rozanov Alexei Sergeyevich , Shedko Elizaveta Dmitrievna , Mescheryakova Irina Anatolyevna , Blinov Alexander Gennadyevich , Korzhuk Anton Vladimirovich , Shlyakhtun Valeria Nikolayevna , Bogacheva Natalia Vladimirovna , Antonov Egor Vladimirovich , Bannikova Svetlana Valerevna , Goryachkovskaya Tatiana Nikolayevna , Peltek Sergey Evgenyevich
Published: November 2022

Neutral protease pAsPs gene was obtained by sequence optimization of NpI protease from Aspergillus pseudotamarii. pAsPs was for the first time integrated in the genome of yeast strain Komagataella phaffii T07, and then produced in a 5 L bioreactor with an enzyme yield of 150,800 U/mL of culture liquid towards casein. The specific activity of the pAsPs was 7,657,000 U/mg toward casein, 2320 U/mg toward hemoglobin, and 25,344 U/mg toward azocasein per 1 mg of the protein. The enzyme was found to be inhibited by Cu2+. Optimal activity pH was shown in the range of pH 6.5–8.0, and optimal temperature—50–60 °C. The molecular mass of the recombinant protease pAsPs was shown to be 67.5 kDa. Mass-spectrometric analysis confirmed the identity of the amino acid sequence of the obtained pAsPs preparation with the predicted sequence, with 17% coverage and protein score 288. Thus, the novel neutral protease pAsPs is a promising candidate for large-scale use in manufacturing, including the food industry.
Synthetic, Cell-Derived, Brain-Derived, and Recombinant β-Amyloid: Modelling Alzheimer’s Disease for Research and Drug Development
Authors: Varshavskaya Kseniya B. , Mitkevich Vladimir A. , Makarov Alexander A. , Barykin Evgeny P.
Published: November 2022

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, characterised by the accumulation of senile plaques and tau tangles, neurodegeneration, and neuroinflammation in the brain. The development of AD is a pathological cascade starting according to the amyloid hypothesis with the accumulation and aggregation of the β-amyloid peptide (Aβ), which induces hyperphosphorylation of tau and promotes the pro-inflammatory activation of microglia leading to synaptic loss and, ultimately, neuronal death. Modelling AD-related processes is important for both studying the molecular basis of the disease and the development of novel therapeutics. The replication of these processes is often achieved with the use of a purified Aβ peptide. However, Aβ preparations obtained from different sources can have strikingly different properties. This review aims to compare the structure and biological effects of Aβ oligomers and aggregates of a higher order: synthetic, recombinant, purified from cell culture, or extracted from brain tissue. The authors summarise the applicability of Aβ preparations for modelling Aβ aggregation, neurotoxicity, cytoskeleton damage, receptor toxicity in vitro and cerebral amyloidosis, synaptic plasticity disruption, and cognitive impairment in vivo and ex vivo. Further, the paper discusses the causes of the reported differences in the effect of Aβ obtained from the sources mentioned above. This review points to the importance of the source of Aβ for AD modelling and could help researchers to choose the optimal way to model the Aβ-induced abnormalities.
Inflammaging: Implications in Sarcopenia
Authors: Antuña Eduardo , Cachán-Vega Cristina , Bermejo-Millo Juan Carlos , Potes Yaiza , Caballero Beatriz , Vega-Naredo Ignacio , Coto-Montes Ana , Garcia-Gonzalez Claudia
Published: November 2022

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as “inflammaging” is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge of the immune system players in skeletal muscle would help to elucidate their implications in sarcopenia. Characterizing the activators of damage sensors and the downstream effectors explains the inference with skeletal muscle performance. Sarcopenia has also been linked to chronic diseases such as diabetes, metabolic syndrome and obesity. Implications of inflammatory signals from these diseases negatively affect skeletal muscle. Autophagic mechanisms are closely related with the inflammasome, as autophagy eliminates stress signaling sent by damage organelles, but also acts with an immunomodulatory function affecting immune cells and cytokine release. The use of melatonin, an antioxidant, ROS scavenger and immune and autophagy modulator, or senotherapeutic compounds targeting senescent cells could represent strategies to counteract inflammation. This review aims to present the many factors regulating skeletal muscle inflammaging and their major implications in order to understand the molecular mechanisms involved in sarcopenia.
Optogenetic Therapy for Visual Restoration
Authors: Sakai Daiki , Tomita Hiroshi , Maeda Akiko
Published: November 2022

Optogenetics is a recent breakthrough in neuroscience, and one of the most promising applications is the treatment of retinal degenerative diseases. Multiple clinical trials are currently ongoing, less than a decade after the first attempt at visual restoration using optogenetics. Optogenetic therapy has great value in providing hope for visual restoration in late-stage retinal degeneration, regardless of the genotype. This alternative gene therapy consists of multiple elements including the choice of target retinal cells, optogenetic tools, and gene delivery systems. Currently, there are various options for each element, all of which have been developed as a product of technological success. In particular, the performance of optogenetic tools in terms of light and wavelength sensitivity have been improved by engineering microbial opsins and applying human opsins. To provide better post-treatment vision, the optimal choice of optogenetic tools and effective gene delivery to retinal cells is necessary. In this review, we provide an overview of the advancements in optogenetic therapy for visual restoration, focusing on available options for optogenetic tools and gene delivery methods.
Study of the Electrochemical Behavior of N-Substituted-4-Piperidones Curcumin Analogs: A Combined Experimental and Theoretical Approach
Authors: Amalraj John , Vergara Claudia E. , Monroy-Cárdenas Matías , Araya-Maturana Ramiro , Martínez-Cifuentes Maximiliano
Published: November 2022

The electrochemical behavior of N-methyl- and N-benzyl-4-piperidone curcumin analogs were studied experimentally and theoretically. The studied compounds present different substituents at the para position in the phenyl rings (-H, -Br, -Cl, -CF3, and -OCH3). We assessed their electrochemical behavior by differential pulse and cyclic voltammetry, while we employed density functional theory (DFT) M06 and M06-2x functionals along with 6-311+G(d,p) basis set calculations to study them theoretically. The results showed that compounds suffer a two-electron irreversible oxidation in the range of 0.72 to 0.86 V, with surface concentrations ranging from 1.72 × 10−7 to 5.01 × 10−7 mol/cm2. The results also suggested that the process is diffusion-controlled for all compounds. M06 DFT calculations showed a better performance than M06-2x to obtain oxidation potentials. We found a good correlation between the experimental and theoretical oxidation potential for N-benzyl-4-piperidones (R2 = 0.9846), while the correlation was poor for N-methyl-4-piperidones (R2 = 0.3786), suggesting that the latter suffer a more complex oxidation process. Calculations of the BDEs for labile C-H bonds in the compounds suggested that neither of the two series of compounds has a different tendency for a proton-coupled electron transfer (PCET) oxidation process. It is proposed that irreversible behavior is due to possible dimerization of the compounds by Shono-type oxidation.
Evaluating and Comparing the Usability of Mobile Banking Applications in Saudi Arabia
Authors: Alhejji Sarah , Albesher Abdulmohsen , Wahsheh Heider , Albarrak Abdulaziz
Published: November 2022

In many countries, the rapid growth of the Internet and mobile technologies has led to the expansion of Internet banking, especially mobile banking. Many banks seek to provide integrated banking services through mobile applications (apps) to increase customer satisfaction and loyalty. A quick look at the reviews of the mobile banking apps in Saudi Arabia reveals different usability issues among these apps. This research analyzed, evaluated, and compared the usability of all Saudi mobile banking apps available for the iOS and Android systems. Usability (as defined by ISO 9241) was measured using three criteria—effectiveness, efficiency, and satisfaction. This research also identified and discussed the most critical weaknesses of the Saudi banks’ apps in regard to providing satisfactory solutions to developers. The results showed that the most critical issues existed in the user interfaces and functionality of the apps, especially those that frequently received updates. Furthermore, the lack of customer support made the interaction between banks and customers weak, leading to customer dissatisfaction.
Transcriptome Analysis and Identification of Chemosensory Genes in Baryscapus dioryctriae (Hymenoptera: Eulophidae)
Authors: Zhu Xiaoyan , Yu Qiling , Gan Xingyu , Song Liwen , Zhang Kaipeng , Zuo Tongtong , Zhang Junjie , Hu Ying , Chen Qi , Ren Bingzhong
Published: November 2022

Baryscapus dioryctriae is a pupal endoparasitoid of many Pyralidae pests and has been used as a biocontrol agent against insect pests that heavily damage the cone and seed of the Korean pine. The olfactory system of wasps plays an essential role in sensing the chemical signals during their foraging, mating, host location, etc., and the chemosensory genes are involved in detecting and transducing these signals. Many chemosensory genes have been identified from the antennae of Hymenoptera; however, there are few reports on the chemosensory genes of Eulophidae wasps. In this study, the transcriptome databases based on ten different tissues of B. dioryctriae were first constructed, and 274 putative chemosensory genes, consisting of 27 OBPs, 9 CSPs, 3 NPC2s, 155 ORs, 49 GRs, 23 IRs and 8 SNMPs genes, were identified based on the transcriptomes and manual annotation. Phylogenetic trees of the chemosensory genes were constructed to investigate the orthologs between B. dioryctriae and other insect species. Additionally, twenty-eight chemosensory genes showed female antennae- and ovipositor-biased expression, which was validated by RT-qPCR. These findings not only built a molecular basis for further research on the processes of chemosensory perception in B. dioryctriae, but also enriched the identification of chemosensory genes from various tissues of Eulophidae wasps.
Pulsed-Field Ablation Using a Novel Ablation-Mapping Integrated System for Pulmonary Vein Isolation—A Preliminary Animal Study
Authors: Zhao Zhihong , Chen Yonggang , Wu Bin , Qiu Gaodong , Hong Liangjie , Chen Xinhua , Zhang Xingwei
Published: November 2022

Objective: The purpose of this study is to evaluate the preliminary safety and effect of a pulsed electric field (PEF) ablation system. Methods: The pulmonary veins (PVs) and superior vena cava (SVC) were isolated with the pulsed field ablation (PFA) system, which included a PEF generator and an electrode. The effects of PFA were investigated in six porcines using a novel circular catheter with combined functions (mapping/ablation) designed to work with a cardiac mapping system. The PEF generator delivered a train of biphasic pulsed electric pulses with a high amplitude (800–2000 V) and short pulse duration. The voltage mapping, PVs and SVC potentials, ostial diameters, and phrenic nerve and esophagus viability data were collected 4 weeks later, after which the animals were subsequently euthanized for gross histopathology analysis. Results: PFA 100% isolated the PVs and SVC with four applications with a mean pulse number of 100–150 pulses, causing no muscle convulsion. PFA does not cause PV stenosis or phrenic nerve dysfunction. Histological analysis confirmed 100% transmurally without any venous stenoses or phrenic injuries. Pathology follow-up showed that PFA had selectively ablated cardiomyocytes but spared blood vessels, the esophagus, and phrenic nerves; after ablation, the myocardial tissue showed homogeneous fibrosis. Conclusion: The PFA system is safe and feasible in the preliminary porcine model, which can effectively isolate PVs and SVCs. Transmural tissue damage can be achieved without phrenic palsy or stenosis.
Prognostic Nutritional Index (PNI) and Neutrophil to Lymphocyte Ratio (NLR) as Predictors of Short-Term Survival in Patients with Advanced Malignant Biliary Obstruction Treated with Percutaneous Transhepatic Biliary Drainage
Authors: Zakosek Milos , Bulatovic Dusan , Pavlovic Vedrana , Filipovic Aleksandar , Igic Aleksa , Galun Danijel , Jovanovic Darko , Sisevic Jelena , Masulovic Dragan
Published: November 2022

Background: Effective biliary tree decompression plays a central role in the palliation of malignant biliary obstruction (MBO). When endoscopic drainage is unfeasible or unsuccessful, percutaneous transhepatic biliary drainage (PTBD) is the method of choice and preferred treatment approach in advanced hilar MBO. The prognostic nutritional index (PNI) reflects the patient’s immunonutritional status, while the neutrophil to lymphocyte ratio (NLR) reflects the patient’s inflammation status. The aim of the present study was to evaluate the prognostic value of preprocedural PNI and NLR on short-term survival in the advanced stage MBO population threatened with PTBD and to characterize the differences in immunonutritional and inflammatory status between 60-day survivors and non-survivors, as well as analyze other variables influencing short-term survival. Methods: This single-center retrospective study was conducted on patients undergoing palliative PTBD caused by MBO as a definitive therapeutic treatment between March 2020 and February 2022. After the procedure, patients were followed until the end of August 2022. Results: A total of 136 patients with malignant biliary obstruction were included in the study. Based on receiver operating characteristic (ROC) curve analysis, optimal cut off-values for NLR (3) and PNI (36.7) were determined. In univariate regression analysis, age, absolute neutrophil count, albumin level, NLR ≤ 3, and PNI ≥ 36.7 were significant predictors of 60-day survival. Level of obstruction and PNI ≥ 36.7 were statistically significant independent predictors of 60-day survival in a multivariate regression model. Using PNI ≥ 36.7 as a significant coefficient from the multivariate regression model with the addition of NLR ≤ 3 from univariate analysis, a 60-day survival score was developed. Conclusions: PNI and NLR are easy to calculate from routine blood analysis, which is regularly conducted for cancer patients. As such, they represent easily available, highly reproducible, and inexpensive tests capable of expressing the severity of systemic inflammatory responses in patients with cancer. Our study highlights that preprocedural PNI and NLR values provide predictors of short-term survival in patients with MBO treated with palliative PTBD. In addition, the proposed 60-day survival score can contribute to better selection of future candidates for PTBD and recognition of high-risk patients with expected poor outcomes.
Annexin A6 Polymorphism Is Associated with Pro-atherogenic Lipid Profiles and with the Downregulation of Methotrexate on Anti-Atherogenic Lipid Profiles in Psoriasis
Authors: Zhang Fuxin , Han Ling , Wang Bing , Huang Qiong , Yawalkar Nikhil , Zhang Zhenghua , Yan Kexiang
Published: November 2022

Background: Annexin A6 (AnxA6) is a lipid-binding protein that regulates cholesterol homeostasis and secretory pathways. However, the correlation of AnxA6 polymorphism with lipometabolism has never been studied in psoriasis. Objectives: To investigate the impact of AnxA6 polymorphism on lipid profiles and the expression of AnxA6 protein in both peripheral blood mononuclear cells (PBMCs) and lipometabolism in psoriasis. Methods: A total of 265 psoriatic patients received methotrexate (MTX) treatment for 12 weeks, after which their lipid profiles were determined by measuring total cholesterol (TC), triglycerides (TGs), lipoprotein (a) [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein (a)1 (ApoA1), and apolipoprotein B (ApoB). In addition, AnxA6 (rs11960458) was genotyped in 262 patients and the expression of AnxA6 in PBMCs was measured by Western blotting at baseline and week 8 post-MTX treatment. Results: The CC genotype carriers of rs11960458 had a lower expression of AnxA6 and lower levels of the pro-atherogenic lipids TC, LDL, and ApoB compared to TC genotype carriers. MTX significantly downregulated the levels of the anti-atherogenic lipids HDL-C and ApoA1 and the level of AnxA6 in TC genotype carriers, as well as the level of TGs in CC genotype carriers. Conclusions: The polymorphism of AnxA6, rs11960458, was statistically associated with the levels of pro-atherogenic lipids and with the downregulation of MTX on the levels of anti-atherogenic lipids and TGs in psoriasis.
The Prevalence of Periodontitis and Assessment of Oral Micro-Biota in Patients with Hidradenitis Suppurativa: A Descriptive Cross-Sectional Study
Authors: Jastrząb Beata , Paśnik-Chwalik Barbara , Konopka Tomasz , Krajewski Piotr K. , Szepietowski Jacek C. , Matusiak Łukasz
Published: November 2022

Periodontitis has been causally connected with the development of other immune-mediated inflammatory disorders previously. Nevertheless, the current literature does not provide knowledge on oral health in hidradenitis suppurativa (HS) individuals. The aim of this study was to assess the prevalence of periodontitis and characterize an oral microbiome in HS patients. Fifty-five patients with HS and fifty-five healthy controls were enlisted in the study. The incidence of periodontitis was assessed in all patients during the periodontal evaluation. RT-PCR tests were used to quantification of bacterial content and assess the number and composition of nine crucial periodontal pathogens. HS patients had a significantly higher prevalence of periodontitis than healthy controls (45.5% versus 14.5%). Significantly higher values of average copy-count numbers of total bacteria were found in HS patients. The majority of periodontal pathogens were more frequently isolated in patients with HS than among controls. The most frequently detected pathogen in the HS group was Treponema denticola (70.9%), whereas among controls Capnocytophaga gingivalis (34.5%) was the most common isolate. There was no correlation between HS severity and the number of DNA copies of periodontal bacteria. The findings of this research suggest that periodontitis may contribute to the development of HS.
A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome
Authors: Filippone Alessia , Ardizzone Alessio , Bova Valentina , Lanza Marika , Casili Giovanna , Cuzzocrea Salvatore , Esposito Emanuela , Campolo Michela , Paterniti Irene
Published: November 2022

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0–4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality.
Microbiome of Acute Otitis Externa
Authors: Kim Sung Kyun , Han Sung Jun , Hong Seok Jin , Hong Seok Min
Published: November 2022

Background: Ear canal skin is directly attached to bone or cartilage, and is also connected to the eardrum. Acute otitis externa is cellulitis of the ear canal skin and subdermal tissue associated with acute inflammation and variable edema. We characterized the microbiome of the normal ear canal and ear canal with otitis externa. Methods: In total, 28 samples (14 each from the ear canal skin of patients with acute otitis externa and normal healthy controls) were collected using swabs. DNA extraction and bacterial microbiome analysis via 16S rRNA gene sequencing were performed. Results: The diversity index (mean amplicon sequence variants and Shannon index) were lower in the otitis externa than control group. According to linear discriminant effect size (LEfSe) analysis, a number of taxa differed significantly between the groups. Pseudomonas at the genus level and Staphylococcus warneri at the species level were identified in the otitis externa group. Conclusion: Our results show the importance of the microbiome in the pathogenesis of otitis externa and provide a basis for treating acute otitis externa by targeting the microbiome.
Safety and Efficacy of the Preserflo® Microshunt in Refractory Glaucoma: A One-Year Study
Authors: Majoulet Alexandre , Scemla Benjamin , Hamard Pascale , Brasnu Emmanuelle , Hage Alexandre , Baudouin Christophe , Labbé Antoine
Published: November 2022

Purpose: To evaluate the safety and efficacy of Preserflo® microshunt implantation in eyes with refractory glaucoma. Methods: In this retrospective study, a cohort of patients who underwent Preserflo® microshunt implantation between April 2019 and August 2020 for refractory glaucoma were evaluated. At the time of surgery, all eyes had uncontrolled intraocular pressure (IOP) despite maximally tolerated medical therapy and at least one previous failed glaucoma filtering surgery. The primary outcome was a complete success, defined as postoperative IOP ≤ 21 mm Hg with an IOP reduction ≥ 20% and no repeat filtering surgery. The secondary outcome was qualified success, defined as a complete success with the use of antiglaucoma medications. The rates of needling, bleb repair, and postoperative complications were also recorded. Results: Forty-seven eyes with a mean preoperative IOP of 30.1 ± 7.1 mm Hg and a mean of 3.4 ± 1 glaucoma medications were included. The mean number of previous surgeries prior to microshunt implantation was 2.3 ± 1.3. After 1 year, the mean IOP was significantly reduced to 18.8 ± 4.6 mm Hg, with the mean number of medications significantly reduced to 1.4 ± 1.2. Complete success was achieved in 35% of eyes, and a qualified success in 60% of eyes. A decrease in IOP of at least 30% was found in 55% of eyes. Needling or bleb repair was performed in 49% of eyes. Complications were minimal and transient, except for one eye which presented with tube extrusion, and another eye with a transected tube. A repeat glaucoma surgery had to be performed in 17% of eyes. Conclusions: The Preserflo® Microshunt provided moderate success but a significant reduction in IOP, with a good safety profile after one year of follow-up in eyes at high risk for failure of filtering surgery.
A Prospective Validation Study of the Functional Bedside Aspiration Screen with Endoscopy: Is It Clinically Applicable in Acute Stroke?
Authors: Kassubek Rebecca , Lindner-Pfleghar Beate , Virvidaki Ioanna Eleni , Kassubek Jan , Althaus Katharina , Weber Antonia Maria , Dimakopoulos Georgios , Milionis Haralampos , Nasios Grigorios
Published: November 2022

The purpose of this study was to investigate the reliability of the novel Functional Bedside Aspiration Screen (FBAS) to predict aspiration risk in acute stroke and to guide initial therapy needs. We conducted a prospective validation study of the FBAS 10-point scale in 101 acute ischemic stroke patients. Outcome measures were compared with the Penetration Aspiration Scale (PAS) via the Flexible Endoscopic Swallowing Study. Correlations with the Functional Oral Intake Scale (FOIS) and the Therapy Requirement Scale (TRS) were analyzed. We observed a 65.8% sensitivity and 70.2% specificity (p = 0.004) for predicting penetration risk (for PAS score ≥ 3) and a 73% sensitivity and 62% specificity for predicting aspiration risk (PAS score ≥ 6). For patients with a modified ranking scale 0–2 (n = 44) on admission, the predictive measurements of the FBAS yielded sensitivity and specificity values of 66.7% and 88.6% (p = 0.011). A significant negative correlation was found with PAS measurements, whereas a positive correlation was observed regarding FOIS. Significantly lower FBAS scores were observed in patients with high requirements for therapeutic interventions and dietary modification. FBAS may be regarded as an alternative time-efficient clinical support tool in settings in which instrumentation is not directly accessible. Further studies including a larger cohort of acute stroke patients with more severe neurological deficits are necessary.
Development and Clinical Trial of a New Orthopedic Surgical Robot for Positioning and Navigation
Authors: Chang Jie , Yu Lipeng , Li Qingqing , Wang Boyao , Yang Lei , Cheng Min , Wang Feng , Zhang Long , Chen Lei , Li Kun , Liang Liang , Zhou Wei , Cai Weihua , Ren Yongxin , Hu Zhiyi , Huang Zhenfei , Sui Tao , Fan Jin , Wang Junwen , Li Bo , Cao Xiaojian , Yin Guoyong
Published: November 2022

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.
Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis
Authors: Gu Shuyan , Hu Xiaoqian , Shi Lizheng , Zhen Xuemei , Sun Xueshan , Huang Minzhuo , Gu Yuxuan , Dong Hengjin
Published: November 2022

Background: There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and compared the treatment effects of glucose-lowering drugs as initial monotherapy for type 2 diabetes. Methods: PubMed, Web of Science, Embase, CNKI, Chongqing VIP, and WanFang Data from 1 January 1990 until 31 December 2020 were searched for randomized controlled trials which compared a glucose-lowering drug with placebo/lifestyle-intervention for type 2 diabetes. Drug classes included metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), glinides (NIDEs), α-glucosidase inhibitors (AGIs), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), insulins (INSs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). Results: A total of 185 trials were included, identifying 38,376 patients from 56 countries across six continents. When choosing an initial drug monotherapy alternative to metformin, SUs were most efficacious in reducing HbA1c (−1.39%; 95% CI −1.63, −1.16) and FPG (−2.70 mmol/L; 95% CI −3.18, −2.23), but increased hypoglycemia risks (5.44; 95% CI 2.11, 14.02). GLP-1RAs were most efficacious in reducing BMI (−1.05 kg/m2; 95% CI −1.81, −0.29) and TC (−0.42 mmol/L; 95% CI −0.61, −0.22). TZDs were most efficacious in increasing HDL-C (0.12 mmol/L; 95% CI 0.07, 0.17). SGLT2is were most efficacious in lowering SBP (−4.18 mmHg; 95% CI −4.84, −3.53). While AGIs conferred higher risk of AE-induced discontinuations (2.57; 95% CI 1.64, 4.03). Overall, only GLP-1RAs showed an integrated beneficial effect on all outcomes. Our results also confirmed the intraclass differences in treatment effects across drugs. Most trials were short-term, and no significant differences in mortality, total vascular events, myocardial infarction, heart failure, stroke, or diabetic nephropathy were observed across drug classes. Conclusions: Our results suggest a potential treatment hierarchy for decision-makers, with GLP-1RAs being the preferred alternative therapy to metformin regarding their favorable efficacy and safety profiles.
Risk Factors for Rapid Recurrence of Hyperkalemia following Cessation of Sodium Zirconium Cyclosilicate
Authors: Imamura Teruhiko , Narang Nikhil , Kinugawa Koichiro
Published: November 2022

Background: Sodium zircon`ium cyclosilicate (SZC), a recently introduced potassium binder, is indicated to treat hyperkalemia. SZC is often terminated soon after the normalization of hyperkalemia in real-world clinical practice. We aimed to investigate the risk factors for the rapid recurrence of hyperkalemia following cessation of SZC. Methods: Patients in whom SZC was discontinued following an improvement in hyperkalemia were followed up for three months. The baseline characteristics that were associated with the rapid recurrence of hyperkalemia (>5.0 mEq/L of serum potassium levels within 3 months) were investigated. Results: A total of 44 patients terminated SZC following the normalization of hyperkalemia. The median age was 81 (69, 87) years old, and 59% were men. When evaluating baseline characteristics, a higher dose of renin-angiotensin system inhibitors was significantly associated with the recurrence of hyperkalemia (adjusted hazard ratio of 1.26, 95% confidence interval 1.02–1.69, p = 0.045) at a designated cutoff of 2.5 mg/day of equivalent enalapril dose. Conclusions: SZC should be considered for ongoing continuation after normalization of hyperkalemia, particularly in patients receiving a relatively higher dose of renin-angiotensin system inhibitors.
Correction: Cicero et al. Long-Term Impact of Different Triple Combination Antihypertensive Medications on Blood Pressure Control, Metabolic Pattern and Incident Events: Data from the Brisighella Heart Study. J. Clin. Med. 2021, 10, 5921
Authors: Cicero Arrigo F. G. , Fogacci Federica , Rizzoli Elisabetta , D’Addato Sergio , Borghi Claudio
Published: November 2022

There was an error in the original publication [...]
Age and Oversizing Influence Iliac Dilatation after EVAR
Authors: Gray Daphne Elisabeth , Samaan Carla , Oikonomou Kyriakos , Gruber-Rouh Tatjana , Schmitz-Rixen Thomas , Derwich Wojciech
Published: November 2022

In the past two decades, endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) has become the first line treatment for infrarenal AAA repair in many countries. While short-term results are good, concerns have been raised about long-term durability. Changes in aortoiliac anatomy, especially at the landing zones, could play a role in EVAR failure over time. The current study aimed to determine certain morphological changes in the distal iliac landing zone after EVAR implantation, as well aspossible risk factors associated with iliac sealing failure. In a retrospective analysis of a tertiary single-centre registry, including patients treated with EVAR between January 2008 and July 2018, clinical follow-up data were assessed, and computer tomography (CT) imaging was evaluated regarding morphological changes in the iliac anatomy during follow-up. For clinical analysis all patients with a minimum follow-up of one year were included; for morphological analysis of iliac anatomy all patients with available CT follow-up of a minimum of one year and a minimum of two CT scans were included. Overall, 127 out of 241 treated patients (92.1% male) were included in the clinical follow-up. Complete CT imaging of 99 iliac arteries in 55 patients was available for morphological analysis. Median postoperative follow-up (FU) for these patients was 33 months (IQR 31; min–max: 12–124). Incidence of type 1b endoleak was 3% but iliac limb detachment from the vessel wall was seen in 18.2% of the target vessels. There was a significant difference in oversizing in iliac limbs with detachment (median 13.9%, IQR 23.1) vs. without detachment (median 23.1%, IQR 19.1) (p = 0.034). Iliac arteries at the landing zone showed a significant diameter increase independent of an endoleak presence (overall cohort median diameter increase at one year 23.1 mm; at two years 0 mm; at three years 4.9 mm). Iliac arteries with detachment (median 14.4%; IQR 23.9) showed a significantly higher diameter increase at the landing zone after four years compared to arteries without detachment (median 5.3%; IQR 9) (p = 0.042). Oversizing correlated positively with an iliac diameter increase at the landing zone over time (3 m: p= 0.001; one year: p < 0.001; two years: p < 0.001; three years: p = 0.006). Older patients showed a significantly lower diameter increase at the distal landing zone over time than younger patients in the first two years after EVAR (p < 0.001/r = −0.606 after two years). In the current study, iliac limb oversizing was associated with increased dilatation of the distal landing zone during a three-year follow-up, while iliac limb detachment was observed less often. An older age was inversely associated to the iliac diameter increase. Future studies should clarify the association between stent graft oversizing, age, and changes in the iliac anatomy in order to identify parameters that affect EVAR durability.
Hypercoagulability and Inflammatory Markers in a Case of Congenital Thrombotic Thrombocytopenic Purpura Complicated by Fetal Demise
Authors: Skeith Leslie , Hurd Kelle , Chaturvedi Shruti , Chow Lorraine , Nicholas Joshua , Lee Adrienne , Young Daniel , Goodyear Dawn , Soucie Jennifer , Girard Louis , Dufour Antoine , Agbani Ejaife O.
Published: November 2022

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder caused by an inherited genetic deficiency of ADAMTS13 and affects less than one per million individuals. Patients who are diagnosed with TTP during pregnancy are at increased risk of maternal and fetal complications including fetal demise. We present a case of a 32-year-old G3P0 (gravida 3, para 0) who presented at 20 weeks gestation with a new diagnosis of congenital TTP (cTTP) and fetal demise. Methods: We describe the pathophysiology of pregnancy complications in a patient with cTTP using platelet procoagulant membrane dynamics analysis and quantitative proteomic studies, compared to four pregnant patients with gestational hypertension, four pregnant patients with preeclampsia, and four healthy pregnant controls. Results: The cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, suggestive of hypercoagulability. Among 15 proteins that were upregulated, S100A8 and S100A9 were distinctly overexpressed. Conclusions: There is platelet-neutrophil activation and interaction, platelet hypercoagulability, and proinflammation in our case of cTTP with fetal demise.
Congested Period in Professional Youth Soccer Players Showed a Different High Decelerations Profile in the Group Performance and a Specific Positional Behaviour
Authors: Muñoz-Castellanos Borja , Rabano-Muñoz Alberto , Requena Bernardo , Suarez-Arrones Luis , Asian-Clemente Jose A.
Published: November 2022

Present soccer demands are increasing in terms of running requirements and the number of matches until youth soccer players experience several periods of fixture congestion during the season. Currently, congested periods have not been extensively studied in this population. For this reason, this study aimed to compare the running demands of professional youth soccer players in congested periods according to their specific playing positions. Twenty youth players were grouped according to their position: Central Defenders (CD), Fullbacks (FB), Midfielders (MF), Wide Midfielders (WM) and Strikers (ST). A GPS system was used to monitor the players during the first (M1), second (M2) and third (M3) matches played during a congested period, measuring their total distance covered (TDC), DC 18.0–20.9 km·h−1, DC 21.0–23.9 km·h−1, DC > 24.0 km·h−1, number of high accelerations (>2.5 m·s−2), number of high decelerations (<2.5 m·s−2) and peak speed (km·h−1). M1, M2 and M3 showed the same TDC, DC 18.0–20.9 km·h−1, DC 21.0–23.9 km·h−1, DC > 24.0 km·h−1, number of high accelerations, and peak speed (p > 0.05). The statistical analysis showed significant differences between M1, M2 and M3 in the decelerations recorded between M1 and M3 (p < 0.05). Likewise, each position showed specific behaviours during the congested period, with all showing at least one difference in DC 18.0–20.9 km·h−1, 21.0–23.9 km·h−1 or >24.0 km·h−1 between M1, M2 and M3 (p < 0.05). In conclusion, coaches should pay attention to the fatigue produced by the number of high decelerations. Secondly, an individualized training protocol should be considered according to the running requirements of each position when youth professional soccer players are involved in a congested period.
An Analytical Symplectic Method for Buckling of Ring-Stiffened Graphene Platelet-Reinforced Composite Cylindrical Shells Subjected to Hydrostatic Pressure
Authors: Sun Zhanzhong , Hu Gangyi , Nie Xueyang , Sun Jiabin
Published: November 2022

In this paper, a novel analytical approach for the buckling of ring-stiffened porous graphene platelet-reinforced composite cylindrical shells under hydrostatic pressure is proposed under the framework of symplectic mechanics. Three types of graphene platelet-reinforced patterns and porosity distributions are considered, and the effective material properties of porous graphene platelet-reinforced composite are determined with a modified Halpin–Tsai model. In the symplectic approach, the governing equations in the conventional Lagrangian system are transformed into a set of Hamiltonian canonical equations, and therefore, the buckling analysis is reduced into an eigenproblem in a symplectic space. Consequently, the accurate critical pressures and corresponding analytical buckling mode shapes are obtained simultaneously without any trial function. The numerical results are compared with the existing results, and good agreements are observed. A comprehensive parametric study of the geometrical parameters, boundary conditions, material properties, and ring-stiffener parameters on the buckling behavior of such shells is also presented.
Multiple F-Box Proteins Collectively Regulate Cell Development and Pathogenesis in the Human Pathogen Cryptococcus neoformans
Authors: Cao Chengjun , Wang Yina , Avina Samantha L. , Walter John , Xue Chaoyang
Published: November 2022

The ubiquitin–proteasome system (UPS) mediates intracellular proteins degradation that influences various cellular functions in eukaryotic cells. The UPS is also involved in the development and virulence of pathogenic fungi. F-box proteins, which are part of the SCF (Skp1-Cullin-F-box protein) ligase, are a key component of UPS and are essential for the recognition of specific substrates. In this study, we identified 20 F-box proteins in C. neoformans and obtained deletion mutants for 19 of them. A comprehensive phenotypic analysis of these mutants revealed the diverse function of F-box proteins in stress response, cell size regulation, sexual reproduction, antifungal drug resistance, and fungal virulence in C. neoformans. The importance of three F-box proteins: Fbp4, Fbp8, and Fbp11, in these cellular functions were characterized in detail. This study provides an overall view of the F-box gene family in C. neoformans, which will lead to a better understanding of the function of fungal SCF E3 ligase-mediated UPS in fungal development and pathogenesis.
The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population
Authors: Verma Anurag , Damrauer Scott M. , Naseer Nawar , Weaver JoEllen , Kripke Colleen M. , Guare Lindsay , Sirugo Giorgio , Kember Rachel L. , Drivas Theodore G. , Dudek Scott M. , Bradford Yuki , Lucas Anastasia , Judy Renae , Verma Shefali S. , Meagher Emma , Nathanson Katherine L. , Feldman Michael , Ritchie Marylyn D. , Rader Daniel J. ,   For The Penn Medicine BioBank
Published: November 2022

The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker data in the PMBB to facilitate discoveries and translational science. To date, 174,712 participants have been enrolled into the PMBB, including approximately 30% of participants of non-European ancestry, making it one of the most diverse medical biobanks. There is a median of seven years of longitudinal data in the EHR available on participants, who also consent to permission to recontact. Herein, we describe the operations and infrastructure of the PMBB, summarize the phenotypic architecture of the enrolled participants, and use body mass index (BMI) as a proof-of-concept quantitative phenotype for PheWAS, LabWAS, and GWAS. The major representation of African-American participants in the PMBB addresses the essential need to expand the diversity in genetic and translational research. There is a critical need for a “medical biobank consortium” to facilitate replication, increase power for rare phenotypes and variants, and promote harmonized collaboration to optimize the potential for biological discovery and precision medicine.
Cardiac Rehabilitation for Older Women with Heart Failure
Authors: Scrutinio Domenico , Guida Pietro , Dalla Vecchia Laura Adelaide , Corrà Ugo , Passantino Andrea
Published: November 2022

Background: the role that sex plays in impacting cardiac rehabilitation (CR) outcomes remains an important gap in knowledge. Methods: we assessed sex differences in clinical and functional outcomes in 2345 older patients with heart failure (HF) admitted to inpatient CR. Three outcomes were considered: (1) the composite outcome of death during the index admission to CR or transfer to acute care; (2) three-year mortality; (3) change in six-minute walking distance (6MWD) from admission to discharge. Sex differences in outcomes were assessed using multivariable Cox or logistic regression models. Results: the hazard ratios of the composite outcome and of three-year mortality for females vs. males were 0.71 (95%CI:0.50–1.00; p = 0.049) and 0.68 (95%CI:0.59–0.79; p < 0.001), respectively. The standardized mean difference in 6MWD increase from admission to discharge between males and females was 0.10. The odds ratio of achieving an increase in 6MWD at discharge to values higher than the optimal sex-specific thresholds for predicting mortality for females vs. males was 2.21 (95%CI:1.53–3.20; p < 0.001). Conclusion: our findings suggest that older females with HF undergoing CR have better prognosis and garner similar improvement in 6MWD compared with their male counterparts. Nonetheless, females were more likely to achieve levels of functional capacity predictive of improved survival.