bluuebunny/crossref_metadata_2025 huggingface dataset:
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Deletion but Not Inhibition of Extracellular PCSK9 Reduces Infarct Sizes Ex Vivo but Not In Vivo
Authors: Schreckenberg Rolf , Wolf Annemarie , Szabados Tamara , Gömöri Kamilla , Szabó István Adorján , Ágoston Gergely , Brenner Gábor , Bencsik Péter , Ferdinandy Péter , Schulz Rainer , Schlüter Klaus-Dieter
Published: June 2022

Hypoxia upregulates PCSK9 expression in the heart, and PCSK9 affects the function of myocytes. This study aimed to investigate the impact of PCSK9 on reperfusion injury in rats and mice fed normal or high-fat diets. Either the genetic knockout of PCSK9 (mice) or the antagonism of circulating PCSK9 via Pep2-8 (mice and rats) was used. Isolated perfused hearts were exposed to 45 min of ischemia followed by 120 min of reperfusion. In vivo, mice were fed normal or high-fat diets (2% cholesterol) for eight weeks prior to coronary artery occlusion (45 min of ischemia) and reperfusion (120 min). Ischemia/reperfusion upregulates PCSK9 expression (rats and mice) and releases it into the perfusate. The inhibition of extracellular PCSK9 does not affect infarct sizes or functional recovery. However, genetic deletion largely reduces infarct size and improves post-ischemic recovery in mice ex vivo but not in vivo. A high-fat diet reduced the survival rate during ischemia and reperfusion, but in a PCSK9-independent manner that was associated with increased plasma matrix metalloproteinase (MMP)9 activity. PCSK9 deletion, but not the inhibition of extracellular PCSK9, reduces infarct sizes in ex vivo hearts, but this effect is overridden in vivo by factors such as MMP9.
Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment
Authors: Lee Ansoo , Choo Hyunah , Jeon Byungsun
Published: June 2022

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. Although there are a couple of FDA (Food and Drug Administration)—approved drugs for ASD treatment such as aripiprazole and risperidone, they are efficient for alleviating aggression, hyperactivity, and self-injury but not the core symptoms. Serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter plays a crucial role in the early neurodevelopmental stage. In particular, 5-HT has been known to regulate a variety of neurobiological processes including neurite outgrowth, dendritic spine morphology, shaping neuronal circuits, synaptic transmission, and synaptic plasticity. Given the roles of serotonergic systems, the 5-HT receptors (5-HTRs) become emerging as potential therapeutic targets in the ASD. In this review, we will focus on the recent development of small molecule modulators of 5-HTRs as therapeutic targets for the ASD treatment.
The Unfolded Protein Response Sensor PERK Mediates Stiffness-Dependent Adaptation in Glioblastoma Cells
Authors: Khoonkari Mohammad , Liang Dong , Lima Marina Trombetta , van der Land Tjitze , Liang Yuanke , Sun Jianwu , Dolga Amalia , Kamperman Marleen , van Rijn Patrick , Kruyt Frank A. E.
Published: June 2022

Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults. In addition to genetic causes, the tumor microenvironment (TME), including stiffening of the extracellular matrix (ECM), is a main driver of GBM progression. Mechano-transduction and the unfolded protein response (UPR) are essential for tumor-cell adaptation to harsh TME conditions. Here, we studied the effect of a variable stiff ECM on the morphology and malignant properties of GBM stem cells (GSCs) and, moreover, examined the possible involvement of the UPR sensor PERK herein. For this, stiffness-tunable human blood plasma (HBP)/alginate hydrogels were generated to mimic ECM stiffening. GSCs showed stiffness-dependent adaptation characterized by elongated morphology, increased proliferation, and motility which was accompanied by F-Actin cytoskeletal remodeling. Interestingly, in PERK-deficient GSCs, stiffness adaptation was severely impaired, which was evidenced by low F-Actin levels, the absence of F-Actin remodeling, and decreased cell proliferation and migration. This impairment could be linked with Filamin-A (FLN-A) expression, a known interactor of PERK, which was strongly reduced in PERK-deficient GSCs. In conclusion, we identified a novel PERK/FLNA/F-Actin mechano-adaptive mechanism and found a new function for PERK in the cellular adaptation to ECM stiffening.
Promoting Consumer Adoption of Electric Vehicles from a Standard-Information-Behavior Perspective
Authors: Sun Weiwei , Yuan Min , Zhang Zheng
Published: June 2022

Consumer adoption of electric vehicles is essentially related to product quality factors, such as safety, performance and compatibility; however, the relationship between product quality standards and consumer behavior is not clear. Based on Multi-Attribute Utility Theory (MAUT) and Prospect Theory, we distinguish claimed quality attributes, intrinsic quality attributes, measured quality attributes and perceived quality attributes and establish a conceptional model using System Dynamics (SD) simulation from the perspective of a Standard-Information-Behavior framework to explore the heterogeneous impacts of technical standards on consumers’ willingness to adopt electric vehicles. Based on the theory model and simulation, we try to explain the heterogeneous effects of three different standards: safety, performance and compatibility. We find that safety standards affect adoption through a market access mechanism, perceived performance of risk standards positively impacts customers’ perceived quality, and compatibility standards influence consumers’ perceived network value. The perceived risk, perceived quality and perceived network value influence consumer adoption willingness and behavior. The study contributes to the theory of innovation diffusion and consumer adoption behavior, and offers insights for standardizing activity, innovation diffusion and marketing product information for electric vehicles.
Multilingual Offline Signature Verification Based on Improved Inverse Discriminator Network
Authors: Xamxidin Nurbiya , Mahpirat  , Yao Zhixi , Aysa Alimjan , Ubul Kurban
Published: June 2022

To further improve the accuracy of multilingual off-line handwritten signature verification, this paper studies the off-line handwritten signature verification of monolingual and multilingual mixture and proposes an improved verification network (IDN), which adopts user-independent (WI) handwritten signature verification, to determine the true signature or false signature. The IDN model contains four neural network streams with shared weights, of which two receiving the original signature images are the discriminative streams, and the other two streams are the reverse stream of the gray inversion image. The enhanced spatial attention models connect the discriminative streams and reverse flow to realize message propagation. The IDN model uses the channel attention mechanism (SE) and the improved spatial attention module (ESA) to propose the effective feature information of signature verification. Since there is no suitable multilingual signature data set, this paper collects two language data sets (Chinese and Uyghur), including 100,000 signatures of 200 people. Our method is tested on the self-built data set and the public data sets of Bengali (BHsig-B) and Hindi (BHsig-H). The method proposed in this paper has the highest discrimination rate of FRR of 10.5%, FAR of 2.06%, and ACC of 96.33% for the mixture of two languages.
On the Use of Mouse Actions at the Character Level
Authors: Navarro Ángel , Casacuberta Francisco
Published: June 2022

Neural Machine Translation (NMT) has improved performance in several tasks up to human parity. However, many companies still use Computer-Assisted Translation (CAT) tools to achieve perfect translation, as well as other tools. Among these tools, we find Interactive-Predictive Neural Machine Translation (IPNMT) systems, whose main feature is facilitating machine–human interactions. In the most conventional systems, the human user fixes a translation error by typing the correct word, sending this feedback to the machine which generates a new translation that satisfies it. In this article, we remove the necessity of typing to correct translations by using the bandit feedback obtained from the cursor position when the user performs a Mouse Action (MA). Our system generates a new translation that fixes the error using only the error position. The user can perform multiple MAs at the same position if the error is not fixed, each of which increases the correction probability. One of the main objectives in the IPNMT field is reducing the required human effort, in order to optimize the translation time. With the proposed technique, an 84% reduction in the number of keystrokes performed can be achieved, while still generating perfect translations. For this reason, we recommend the use of this technique in IPNMT systems.
On the Malleability of Consumer Attitudes toward Disruptive Technologies: A Pilot Study of Cryptocurrencies
Authors: Treiblmaier Horst , Gorbunov Evgeny
Published: June 2022

The digital transformation of core marketing activities substantially impacts relations between consumers and companies. Novel technologies are usually complex, making their underlying functionality as well as the desirable and undesirable implications hard to grasp for ordinary consumers. Cryptocurrencies are a prominent yet controversial and poorly understood example of an innovation that may transform companies’ future marketing activities. In this study, we investigate how easily consumers’ attitudes toward cryptocurrencies can be shaped by splitting a convenience sample of 100 consumers into two equal groups and exposing them to true, but biased, information about cryptocurrencies (including market forecasts), respectively, highlighting either the advantages or disadvantages of the technology. We subsequently found a significant difference in the trust, security and risk perceptions between the two groups; specifically, more positive attitudes pertaining to trust, security, risk and financial gains prevailed in the group exposed to positively-skewed information, while perceptions regarding trust, risk and the sustainability of cryptocurrencies were weaker among the group exposed to negatively-skewed information. These findings reveal some important insights into how easily consumer attitudes toward new technologies can be shaped through the presentation of lopsided information and call for further in-depth research in this important yet under-researched field.
Pseudo-Tetrahedral Copper(I) Symmetrical Formamidine Dithiocarbamate-Phosphine Complexes: Antibacterial, Antioxidant and Pharmacokinetics Studies
Authors: Oladipo Segun D. , Omondi Bernard
Published: June 2022

Three copper(I) dithiocarbamate–phosphine complexes of the general formula Cu(PPh3)2L were synthesized by metathesis reactions of the potassium salt of the dithiocarbamate ligand L and the precursor complex Cu(PPh3)2NO3 in an equimolar ratio. L represents N,N′-bis(2,6-dimethylphenyl)formamidine dithiocarbamate L1 in complex 1, N,N′-bis(2,6-disopropylphenyl) formamidine dithiocarbamate L2 in complex 2, and N,N′-dimesitylformamidine dithiocarbamate L3 in complex 3. The single-crystal X-ray structure revealed the coordination of the copper atom to two sulfur atoms of the dithiocarbamates, as well as two phosphorus atoms of the PPh3 units, which resulted in distorted tetrahedral geometries. The calculated τ4 (tau factor) values for 1, 2 and 3 were 0.82, 0.81 and 0.85, respectively, confirming the pseudo-tetrahedral geometry proposed. Complexes 1–3 showed remarkable luminescent properties in CH2Cl2 at room temperature. All three complexes showed moderate-to-low antibacterial potential against Gram-negative bacteria, while none of the complexes were active against Gram-positive bacteria. The DPPH assay studies showed that complex 2 had the lowest IC50 (4.99 × 10−3 mM),and had higher DPPH free radical scavenging ability than 1 and 3. The pharmacological estimations of 1–3 showed that all of the complexes showed minimal violation of Lipinski’s rule.
Current Status of Mosquito Handling, Transporting and Releasing in Frame of the Sterile Insect Technique
Authors: Guo Jiatian , Zheng Xiaoying , Zhang Dongjing , Wu Yu
Published: June 2022

The sterile insect technique (SIT) and its related technologies are considered to be a powerful weapon for fighting against mosquitoes. As an important part of the area-wide integrated pest management (AW-IPM) programs, SIT can help reduce the use of chemical pesticides for mosquito control, and consequently, the occurrence of insecticide resistance. The mosquito SIT involves several important steps, including mass rearing, sex separation, irradiation, packing, transportation, release and monitoring. To enable the application of SIT against mosquitoes to reduce vector populations, the Joint Food and Agriculture Organization of the United Nations (FAO) and the International Atomic Energy Agency (IAEA) Centre (previously called Division) of Nuclear Techniques in Food and Agriculture (hereinafter called Joint FAO/IAEA Centre) and its Insects Pest Control sub-program promoted a coordinated research project (CRP) entitled “Mosquito handling, transport, release and male trapping methods” to enhance the success of SIT. This article summarizes the existing explorations that are critical to the handling and transporting of male mosquitoes, offers an overview of detailed steps in SIT and discusses new emerging methods for mosquito releases, covering most processes of SIT.
Blitz Vision: Development of a New Full-Electric Sports Sedan Using QFD, SDE and Virtual Prototyping
Authors: Frizziero Leonardo , Galletti Ludovico , Magnani Lorenzo , Meazza Edoardo Gaetano , Freddi Marco
Published: June 2022

In this paper, industrial design structure (IDeS) is applied for the development of two new full-electric sports sedan car proposals that go by the names Blitz Vision AS and Retro. With a deep analysis of the trends dominating the automotive industry, a series of product requirements was identified using quality function deployment (QFD). The results of such analysis led to the definition of the technical specifications of the product via benchmarking (BM) and top-flop analysis (TFA). The product architecture was then defined by making use of a modular platform chassis capable of housing a variety of vehicle bodyworks. The structured methodology of stylistic design engineering (SDE) was used. This can be divided in six phases: (1) stylistic trends analysis; (2) sketches; (3) 2D CAD drawings; (4) 3D CAD models; (5) virtual prototyping; (6) solid stylistic model. The chassis of the CAD model was verified structurally by means of FEM analysis, whereas the drag coefficients of the two vehicle proposals were compared with one of the main competitor’s vehicles via CFD simulations. The resulting car models are both aesthetically appealing and can be further developed, leading eventually to the production stage. This proves the effectiveness of IDeS and SDE in car design.
Laparoscopic and Robot-Assisted Hepatic Surgery: An Historical Review
Authors: Shimizu Atsushi , Ito Miwa , Lefor Alan Kawarai
Published: June 2022

Hepatic surgery is a rapidly expanding component of abdominal surgery and is performed for a wide range of indications. The introduction of laparoscopic cholecystectomy in 1987 was a major change in abdominal surgery. Laparoscopic surgery was widely and rapidly adopted throughout the world for cholecystectomy initially and then applied to a variety of other procedures. Laparoscopic surgery became regularly applied to hepatic surgery, including segmental and major resections as well as organ donation. Many operations progressed from open surgery to laparoscopy to robot-assisted surgery, including colon resection, pancreatectomy, splenectomy thyroidectomy, adrenalectomy, prostatectomy, gastrectomy, and others. It is difficult to prove a data-based benefit using robot-assisted surgery, although laparoscopic and robot-assisted surgery of the liver are not inferior regarding major outcomes. When laparoscopic surgery initially became popular, many had concerns about its use to treat malignancies. Robot-assisted surgery is being used to treat a variety of benign and malignant conditions, and studies have shown no deterioration in outcomes. Robot-assisted surgery for the treatment of malignancies has become accepted and is now being used at more centers. The outcomes after robot-assisted surgery depend on its use at specialized centers, the surgeon’s personal experience backed up by extensive training and maintenance of international registries. Robot-assisted hepatic surgery has been shown to be associated with slightly less intraoperative blood loss and shorter hospital lengths of stay compared to open surgery. Oncologic outcomes have been maintained, and some studies show higher rates of R0 resections. Patients who need surgery for liver lesions should identify a surgeon they trust and should not be concerned with the specific operative approach used. The growth of robot-assisted surgery of the liver has occurred in a stepwise approach which is very different from the frenzy that was seen with the introduction of laparoscopic cholecystectomy. This approach allowed the identification of areas for improvement, many of which are at the nexus of engineering and medicine. Further improvements in robot-assisted surgery depend on the combined efforts of engineers and surgeons.
The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients
Authors: Colaci Michele , Zanoli Luca , Lo Gullo Alberto , Sambataro Domenico , Sambataro Gianluca , Aprile Maria Letizia , Castellino Pietro , Malatino Lorenzo
Published: June 2022

(1) Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibrosis of skin and visceral organs. In the last decade, attention has been focused on the macrovascular involvement of the disease. In particular, the observation of increased arterial stiffness represented an interesting aspect of the disease, as predictor of cardiovascular risk. (2) Methods: We recruited 60 SSc patients (52 ± 12 years old, 90% females) and 150 age/sex-matched healthy controls in order to evaluate both intima-media thickness of the right common carotid artery and arterial stiffness using the B-mode echography and the SphygmoCor system® tonometer. (3) Results: The carotid-femoral pulse wave velocity (PWV) was higher in SSc patients than in controls (8.6 ± 1.7 vs. 7.8 ± 1.5 m/s; p < 0.001), as was the carotid-radial PWV (7.8 ± 1.1 vs. 6.7 ± 1.4 m/s; p < 0.001). The intima-media thickness was higher in SSc than in controls (654 ± 108 vs. 602 ± 118 µm; p = 0.004). The other parameters measured at carotid (radial strain, Young’s modulus, compliance and distensibility) all indicated that arterial stiffness in tension was more pronounced in SSc. Of interest, the direct correlation between PWV and age corresponded closely in SSc. Moreover, a significant difference between SSc and controls as regards the carotid parameters was evident in younger subjects. (4) Conclusions: SSc patients showed an increased arterial stiffness compared to healthy controls. In particular, an SSc-related pathologic effect was suggested by the more pronounced increase in PWV with age and lower values of carotid elasticity in younger SSc patients than in age-matched controls.
Gene Expression Profiling in Abdominal Aortic Aneurysms
Authors: Behrens Amelie L. , Dihlmann Susanne , Grond-Ginsbach Caspar , Peters Andreas S. , Dorweiler Bernhard , Böckler Dittmar , Erhart Philipp
Published: June 2022

Gene expression profiling of abdominal aortic aneurysms (AAA) indicates that chronic inflammatory responses, active matrix metalloproteinases, and degradation of the extracellular matrix components are involved in disease development and progression. This study investigates intra- and interpersonal RNA genome-wide expression profiling differences (Illumina HumanHT-12, BeadCHIP expression) of 24 AAA biopsies from 12 patients using a single gene and pathway (GeneOntology, GO enrichment) analysis. Biopsies were collected during open surgical AAA repair and according to prior finite element analysis (FEA) from regions with the highest and lowest wall stress. Single gene analysis revealed a strong heterogeneity of RNA expression parameters within the same and different AAA biopsies. The pathway analysis of all samples showed significant enrichment of genes from three different signaling pathways (integrin signaling pathway: fold change FC 1.63, p = 0.001; cholecystokinin receptor pathway: FC 1.60, p = 0.011; inflammation mediated by chemokine signaling pathway: FC 1.45, p = 0.028). These results indicate heterogeneous gene expression patterns within the AAA vascular wall. Single biopsy investigations do not permit a comprehensive characterization of activated molecular processes in AAA disease.
Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes
Authors: Tarkowska Agata , Furmaga-Jabłońska Wanda , Bogucki Jacek , Kocki Janusz , Pluta Ryszard
Published: June 2022

In this study, the expression of the genes of the amyloid protein precursor, β-secretase, presenilin 1 and 2 by RT-PCR in the lymphocytes of newborns after perinatal asphyxia and perinatal asphyxia treated with hypothermia was analyzed at the age of 15–21 days. The relative quantification of Alzheimer’s-disease-related genes was first performed by comparing the peripheral lymphocytes of non-asphyxia control versus those with asphyxia or asphyxia with hypothermia. In the newborns who had perinatal asphyxia, the peripheral lymphocytes presented a decreased expression of the amyloid protein precursor and β-secretase genes. On the other hand, the expression of the presenilin 1 and 2 genes increased in the studied group. The expression of the studied genes in the asphyxia group treated with hypothermia had an identical pattern of changes that were not statistically significant to the asphyxia group. This suggests that the expression of the genes involved in the metabolism of the amyloid protein precursor in the peripheral lymphocytes may be a biomarker of progressive pathological processes in the brain after asphyxia that are not affected by hypothermia. These are the first data in the world showing the role of hypothermia in the gene changes associated with Alzheimer’s disease in the peripheral lymphocytes of newborns after asphyxia.
Examining the Autonomic Nervous System in the Relationship among Heart Rate Variability, Stress Coping, and Cognitive Ability in Individuals with Psychiatric Disorders
Authors: Lenger Melanie , Dalkner Nina , Schwalsberger Karin , Hagendorfer Bianca , Schönthaler Elena , Rieger Alexandra , Maget Alexander , Fellendorf Frederike , Hamm Carlo , Gramer Margit , Hufnagl Alois , Reininghaus Bernd , Reininghaus Eva
Published: June 2022

Depression is one of the most severe psychiatric disorders and affects patients on emotional, physical, and cognitive levels. Comorbid somatic conditions, such as cardiovascular diseases, are frequent and affect the quality of life, as well as mortality. Underlying maladaptive autonomic nervous system regulation influences emotional and cognitive processes. This study, thus, aimed to investigate the relationship among heart rate variability (HRV), self-reported coping strategies, executive function, and inhibition in individuals with psychiatric disorders. Data of 97 patients treated in a multi-professional psychiatric rehabilitation center for 6 weeks were analyzed. Subjects underwent psychological tests (Stress Coping Style Questionnaire, Emotional Competence Questionnaire, and Becks Depression Inventory-II), a cognitive test (Color-Word Interference Test), and a 24 h electrocardiogram to record HRV. Patients with higher depression scores had significantly lower HRVs and decreased self-reported abilities for stress coping. Depression severity did not affect cognitive inhibitory abilities. HRV was related to neither coping strategies nor cognitive inhibition abilities. However, lower HRV was related to higher values of Negative Stress Coping (β = −0.21, p < 0.05). This relationship was fully mediated by depression severity (−4.79, 95% CI: −8.72, −0.72). HRV is not related to quantitative cognitive inhibition, but to the self-reported ability to cope with negative emotions in individuals with psychiatric disorders.
Platelet Reactivity and Outcomes after Off-Pump Coronary Surgery in Acute Coronary Syndrome Patients
Authors: Soh Sarah , Shin Yu Rim , Song Jong-Wook , Choi Jun Hyug , Kwak Young-Lan , Shim Jae-Kwang
Published: June 2022

Ischemic and hemorrhagic complications are major determinants of survival in acute coronary syndrome (ACS) patients undergoing coronary surgery. We investigated the association of preoperative platelet reactivity to P2Y12 antagonists with ischemic and hemorrhagic complications after Off-Pump Coronary Artery Bypass surgery (OPCAB) in ACS patients who received dual anti-platelet therapy (DAPT) within 5 days prior to surgery. This prospective, observational study with 177 patients compared the incidence of perioperative major bleeding and major adverse cardiac events (MACEs) in relation to the tertile distribution of the % inhibitory response to P2Y12 antagonists, as measured by a thromboelastography platelet mapping assay. The incidences of perioperative major bleeding and MACEs were similar in relation to the tertile distribution of inhibitory response to P2Y12 antagonists. The % inhibitory responses to P2Y12 antagonists between patients who did or did not exhibit MACEs, and with or without major bleeding, were 58 ± 20% and 56 ± 20% (p = 0.578) and 57 ± 19% and 56 ± 21% (p = 0.923), respectively. In ACS patients who received DAPT close to OPCAB, the platelet inhibitory response to P2Y12 antagonists was not associated with ischemic or hemorrhagic complications. OPCAB may obviate the need for routine platelet function testing for ACS patients requiring DAPT and surgical revascularization. Clinical Registration Number: NCT02184884.
When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD
Authors: Rojano-Toimil Alba , Rivera-Esteban Jesús , Manzano-Nuñez Ramiro , Bañares Juan , Martinez Selva David , Gabriel-Medina Pablo , Ferrer Roser , Pericàs Juan M , Ciudin Andreea
Published: June 2022

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.
Fourteen-Year Temporal Trends in Patients Hospitalized for Mitral Regurgitation: The Increasing Burden of Mitral Valve Prolapse in Men
Authors: Grave Clémence , Tribouilloy Christophe , Tuppin Philippe , Weill Alain , Gabet Amélie , Juillière Yves , Cinaud Alexandre , Olié Valérie
Published: June 2022

Mitral regurgitation (MR) is the second most common valvular heart disease in Europe. The aging of the population and the increase in post-infarction survival could increase the prevalence of MR. To estimate the burden of patients hospitalized for MR in France in 2019 and temporal trends by etiology and sex from 2006 to 2020, we selected all patients hospitalized for MR using the national hospital database. In 2019, 49.2% of such patients had mitral valve prolapse (MVP), 17.1% had ischemic MR, 9.9% had rheumatic MR and 4.4% had MR with cardiomyopathy. The mean age of MVP patients was 67.8 years, and 34% were women. Among 89% of MVP inpatients who had received mitral valve repair or replacement, 55% received surgical repair, 13% received percutaneous repair and 25% received replacement. The all-cause mortality of one year after a mitral procedure of MVP was 5.4%. Among ischemic MR inpatients, 29% have had a mitral valve replacement, 16% a surgical repair and 19% a percutaneous repair. Between 2006 and 2019, the age-standardized rates of patients hospitalized for MVP have increased by 60%, especially in men (+80%) with 5.3/100,000 Person-Years (PY). The age-standardized rates of patients hospitalized for ischemic MR have increased by 25% with 1.8/100,000 PY; that of rheumatic MR has decreased by 36%. The study found that the burden of MVP in hospitals has increased substantially, especially among men. These results emphasize the need to monitor these temporal trends and anticipate care needs in the coming years.
Human Amniotic Suspension Allograft Improves Pain and Function in Knee Osteoarthritis: A Prospective Not Randomized Clinical Pilot Study
Authors: Natali Simone , Farinelli Luca , Screpis Daniele , Trojan Diletta , Montagner Giulia , Favaretto Francesca , Zorzi Claudio
Published: June 2022

Osteoarthritis (OA) is a chronic debilitating disorder causing pain and gradual degeneration of joints. Among various cell therapies, mesenchymal stem cell (MSC) therapy appears to provide encouraging results. Human amniotic suspension allografts (HASA) have anti-inflammatory and chondroregenerative potential and represent a promising treatment strategy. The purpose of the present study was to prospectively assess the safety, clinical effectiveness, and feasibility of intra-articular injections of human amniotic suspension allograft (HASA) in unilateral knee OA in order to assess the improvement of symptoms and delay the necessity for invasive surgical procedures. A total of 25 symptomatic patients, affected by knee OA were treated with 3 mL of HASA. Clinical evaluations before the treatment and after 3, 6, and 12 months were performed through International Knee Documentation Committee (IKDC) score and Visual Analogue Scale (VAS) scores. Adverse events were recorded. No severe complications were noted during the treatment and the follow-up period. A statistically significant improvement from basal evaluation to the 3-, 6-, and 12-month follow-up visits was observed. The present pilot study indicates that a single intra-articular injection of HASA seems safe and able to provide positive clinical outcomes, potentially offering a new minimally invasive therapeutic option for patients with knee OA.
Endpoints in Dysphagia Trials. Comment on Speyer et al. Neurostimulation in People with Oropharyngeal Dysphagia: A Systematic Review and Meta-Analyses of Randomised Controlled Trials—Part I: Pharyngeal and Neuromuscular Electrical Stimulation. J. Clin. Med. 2022, 11, 776
Authors: Dziewas Rainer , Bath Philip M.
Published: June 2022

We read with interest the authors’ systematic review and meta-analysis of pharyngeal electrical stimulation (PES) and neuromuscular electrical stimulation (NMES) in patients with oropharyngeal dysphagia (OD) [...]
Prediction of White Matter Hyperintensity in Brain MRI Using Fundus Photographs via Deep Learning
Authors: Cho Bum-Joo , Lee Minwoo , Han Jiyong , Kwon Soonil , Oh Mi Sun , Yu Kyung-Ho , Lee Byung-Chul , Kim Ju Han , Kim Chulho
Published: June 2022

Purpose: We investigated whether a deep learning algorithm applied to retinal fundoscopic images could predict cerebral white matter hyperintensity (WMH), as represented by a modified Fazekas scale (FS), on brain magnetic resonance imaging (MRI). Methods: Participants who had undergone brain MRI and health-screening fundus photography at Hallym University Sacred Heart Hospital between 2010 and 2020 were consecutively included. The subjects were divided based on the presence of WMH, then classified into three groups according to the FS grade (0 vs. 1 vs. 2+) using age matching. Two pre-trained convolutional neural networks were fine-tuned and evaluated for prediction performance using 10-fold cross-validation. Results: A total of 3726 fundus photographs from 1892 subjects were included, of which 905 fundus photographs from 462 subjects were included in the age-matched balanced dataset. In predicting the presence of WMH, the mean area under the receiver operating characteristic curve was 0.736 ± 0.030 for DenseNet-201 and 0.724 ± 0.026 for EfficientNet-B7. For the prediction of FS grade, the mean accuracies reached 41.4 ± 5.7% with DenseNet-201 and 39.6 ± 5.6% with EfficientNet-B7. The deep learning models focused on the macula and retinal vasculature to detect an FS of 2+. Conclusions: Cerebral WMH might be partially predicted by non-invasive fundus photography via deep learning, which may suggest an eye–brain association.
Effects of Smart Drugs on Cholinergic System and Non-Neuronal Acetylcholine in the Mouse Hippocampus: Histopathological Approach
Authors: Satoh Ryusei , Kawakami Kiyoharu , Nakadate Kazuhiko
Published: June 2022

In recent years, people in the United States and other countries have been using smart drugs, called nootropic or cognitive enhancers, to improve concentration and memory learning skills. However, these drugs were originally prescribed for attention-deficit hyperactivity disorder and dementia, and their efficacy in healthy people has not yet been established. We focused on acetylcholine in the hippocampus, which is responsible for memory learning, and elucidate the long-term effects of smart drugs on the neural circuits. Smart drugs were administered orally in normal young mice for seven weeks. The hippocampus was sectioned and compared histologically by hematoxylin and eosin (HE) staining, immunohistochemistry for acetylcholine, and immunoelectron microscopy. There were no significant changes in acetylcholinesterase staining. However, in HE, we found perivascular edema, and choline acetyltransferase staining showed increased staining throughout the hippocampus and new signal induction in the perivascular area in the CA3, especially in the aniracetam and α-glyceryl phosphoryl choline group. Additionally, new muscarinic acetylcholine receptor signals were observed in the CA1 due to smart drug intake, suggesting that vasodilation might cause neuronal activation by increasing the influx of nutrients and oxygen. Moreover, these results suggest a possible new mechanism of acetylcholine-mediated neural circuit activation by smart drug intake.
Model Informed Precision Dosing Tool Forecasts Trough Infliximab and Associates with Disease Status and Tumor Necrosis Factor-Alpha Levels of Inflammatory Bowel Diseases
Authors: Primas Christian , Reinisch Walter , Panetta John C. , Eser Alexander , Mould Diane R. , Dervieux Thierry
Published: June 2022

Background: Substantial inter-and intra-individual variability of Infliximab (IFX) pharmacokinetics necessitates tailored dosing approaches. Here, we evaluated the performances of a Model Informed Precision Dosing (MIPD) Tool in forecasting trough Infliximab (IFX) levels in association with disease status and circulating TNF-α in patients with Inflammatory Bowel Diseases (IBD). Methods: Consented patients undergoing every 8-week maintenance therapy with IFX were enrolled. Midcycle specimens were collected, IFX, antibodies to IFX, albumin were determined and analyzed with weight using nonlinear mixed effect models coupled with Bayesian data assimilation to forecast trough levels. Accuracy of forecasted as compared to observed trough IFX levels were evaluated using Demings’s regression. Association between IFX levels, CRP-based clinical remission and TNF-α levels were analyzed using logistic regression and linear mixed effect models. Results: In 41 patients receiving IFX (median dose = 5.3 mg/Kg), median IFX levels decreased from 13.0 to 3.9 µg/mL from mid to end of cycle time points, respectively. Midcycle IFX levels forecasted trough with Deming’s slope = 0.90 and R2 = 0.87. Observed end cycle and forecasted trough levels above 5 µg/mL associated with CRP-based clinical remission (OR = 7.2 CI95%: 1.7–30.2; OR = 21.0 CI95%: 3.4–127.9, respectively) (p < 0.01). Median TNF-α levels increased from 4.6 to 8.0 pg/mL from mid to end of cycle time points, respectively (p < 0.01). CRP and TNF-α levels associated independently and additively to decreased IFX levels (p < 0.01). Conclusions: These data establish the value of our MIPD tool in forecasting trough IFX levels in patients with IBD. Serum TNF-α and CRP are reflective of inflammatory burden which impacts exposure.
Levels of lncRNA GAS5 in Plasma of Patients with Severe Traumatic Brain Injury: Correlation with Systemic Inflammation and Early Outcome
Authors: Lei Jin , Zhang Xiao , Tan Rui , Li Yu , Zhao Kai , Niu Hongquan
Published: June 2022

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132–0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025–7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719–0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651–0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767–0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.
Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies
Authors: Xu Ran , Rösler Judith , Teich Wanda , Radke Josefine , Früh Anton , Scherschinski Lea , Onken Julia , Vajkoczy Peter , Misch Martin , Faust Katharina
Published: June 2022

The utilization of fluorescein-guided biopsies has recently been discussed to improve and expedite operative techniques in the detection of tumor-positive tissue, as well as to avoid making sampling errors. In this study, we aimed to report our experience with fluorescein-guided biopsies and elucidate distribution patterns in different histopathological diagnoses in order to develop strategies to increase the efficiency and accuracy of this technique. We report on 45 fluorescence-guided stereotactic biopsies in 44 patients (15 female, 29 male) at our institution from March 2016 to March 2021, including 25 frame-based stereotactic biopsies and 20 frameless image-guided biopsies using VarioGuide®. A total number of 347 biopsy samples with a median of 8 samples (range: 4–18) per patient were evaluated for intraoperative fluorescein uptake and correlated to definitive histopathology. The median age at surgery was 63 years (range: 18–87). Of the acquired specimens, 63% were fluorescein positive. Final histopathology included glioblastoma (n = 16), B-cell non-Hodgkin lymphoma (n = 10), astrocytoma, IDH-mutant WHO grade III (n = 6), astrocytoma, IDH-mutant WHO grade II (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted WHO grade II (n = 2), reactive CNS tissue/inflammation (n = 4), post-transplantation lymphoproliferative disorder (PTLD; n = 2), ependymoma (n = 1), infection (toxoplasmosis; n = 1), multiple sclerosis (n = 1), and metastasis (n = 1). The sensitivity for high-grade gliomas was 85%, and the specificity was 70%. For contrast-enhancing lesions, the specificity of fluorescein was 84%. The number needed to sample for contrast-enhancing lesions was three, and the overall number needed to sample for final histopathological diagnosis was five. Interestingly, in the astrocytoma, IDH-mutant WHO grade III group, 22/46 (48%) demonstrated fluorescein uptake despite no evidence for gadolinium uptake, and 73% of these were tumor-positive. In our patient series, fluorescein-guided stereotactic biopsy increases the likelihood of definitive neuropathological diagnosis, and the number needed to sample can be reduced by 50% in contrast-enhancing lesions.
A Watch-Type Electrocardiography Is a Reliable Tool for Detecting Paroxysmal Cardiac Arrhythmias
Authors: Kim Yun Gi , Choi Jong-Il , Kim Hee-Jung , Min Kyongjin , Choi Yun Young , Shim Jaemin , Son Ho Sung , Kim Young-Hoon
Published: June 2022

Background: A substantial proportion of cardiac arrhythmias are paroxysmal in nature, and 12-lead electrocardiography (ECG) and Holter monitoring often fail to detect paroxysmal arrhythmias. We designed and evaluated a watch-type, electrocardiograph-recording, wearable device (w-ECG) to overcome the limitations of 12-lead ECG and Holter monitoring. Methods: We prospectively enrolled 96 patients with symptoms assumed to be related to cardiac arrhythmias. Electrocardiography recording was performed with both the w-ECG and Holter monitoring. Detection of any arrhythmia was the primary outcome endpoint and was compared between the w-ECG and Holter monitoring. Results: Any arrhythmia was detected in 51 (53.1%) and 27 (28.1%) patients by the w-ECG and Holter monitoring, respectively (odds ratio (OR) = 2.9, p < 0.001). The w-ECG was superior to Holter monitoring for the detection of clinically significant arrhythmias (excluding atrial premature contraction, ventricular premature contraction, and non-sustained atrial tachyarrhythmia) (OR = 2.34, p = 0.018). In 27 (28.1%) patients, cardiac arrhythmias were detected only by the w-ECG, with atrial fibrillation being the most frequent case (13 patients). Based on ECGs recorded by using the w-ECG, 17 patients (17.7%) received therapeutic interventions, including radiofrequency catheter ablation. Conclusions: The w-ECG is capable of recording ECGs of good quality, with a discernable P wave and distinguishable QRS morphology. The ability of the w-ECG to detect cardiac arrhythmias was significantly better than that of Holter monitoring, and a significant proportion of patients received therapeutic intervention based on ECGs recorded by the w-ECG.
Supervised Physiotherapy Improves Three-Dimensional (3D) Gait Parameters in Patients after Surgical Suturing of the Achilles Tendon Using an Open Method (SSATOM)
Authors: Czamara Andrzej , Sikorski Łukasz
Published: June 2022

Background: The aim of this study was to assess the effectiveness of 38 supervised postoperative physiotherapy (SVPh) visits conducted between 1 and 20 weeks after SSATOM on the values of 3D gait parameters measured at 10 and 20 weeks after surgery. Material: Group I comprised male patients (n = 22) after SSATOM (SVPh x = 38 visits) and Group II comprised male patients (n = 22) from the control group. Methods: A non-randomized, open-label, controlled clinical trial was performed in the two groups to obtain the following values: Step length (cm), stride length (cm), step width (cm), next stance phase (%), swing phase (%), double support (%), gait velocity (m/s), and walking frequency (step/min). The measurements were carried out using the BTS SMART system (Italy). Results: Orthopedic examination showed no pain, a negative result of Thompson and Matles tests, and proper healing of Achilles tendon (ultrasound image). In Group I, between 10 and 20 weeks after SSATOM, there was a statistically significant improvement in all tested gait parameter values (p ≤ 0.001 to 0.009). Conclusions: Conducting 38 SVPh visits significantly improved the values of the analyzed kinematic and spatiotemporal gait parameters in patients in the twentieth week after SSATOM, which were mostly close to the non-operated side and the results of the control group. However, the gait speed and stride length were not close to the results of the control group.
Changes of Acute Kidney Injury Epidemiology during the COVID-19 Pandemic: A Retrospective Cohort Study
Authors: Esposito Pasquale , Russo Elisa , Picciotto Daniela , Cappadona Francesca , Battaglia Yuri , Traverso Giovanni Battista , Viazzi Francesca
Published: June 2022

To evaluate the impact of the Coronavirus Disease-19 (COVID-19) pandemic on the epidemiology of acute kidney injury (AKI) in hospitalized patients, we performed a retrospective cohort study comparing data of patients hospitalized from January 2016 to December 2019 (pre-COVID-19 period) and from January to December 2020 (COVID-19 period, including both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative and positive patients). AKI was classified by evaluating the kinetics of creatinine levels. A total of 51,681 patients during the pre-COVID-19 period and 10,062 during the COVID-19 period (9026 SARS-CoV-2-negative and 1036 SARS-CoV-2-positive) were analyzed. Patients admitted in the COVID-19 period were significantly older, with a higher prevalence of males. In-hospital AKI incidence was 31.7% during the COVID-19 period (30.5% in SARS-CoV-2-negative patients and 42.2% in SARS-CoV-2-positive ones) as compared to 25.9% during the pre-COVID-19 period (p < 0.0001). In the multivariate analysis, AKI development was independently associated with both SARS-CoV-2 infection and admission period. Moreover, evaluating the pre-admission estimated glomerular filtration rate (eGFR) we found that during the COVID-19 period, there was an increase in AKI stage 2–3 incidence both in patients with pre-admission eGFR < 60 mL/min/1.73 m2 and in those with eGFR ≥ 60 mL/min/1.73 m2 (“de novo” AKI). Similarly, clinical outcomes evaluated as intensive care unit admission, length of hospital stay, and mortality were significantly worse in patients admitted in the COVID-19 period. Additionally, in this case, the mortality was independently correlated with the admission during the COVID-19 period and SARS-CoV-2 infection. In conclusion, we found that during the COVID-19 pandemic, in-hospital AKI epidemiology has changed, not only for patients affected by COVID-19. These modifications underline the necessity to rethink AKI management during health emergencies.