bluuebunny/crossref_metadata_2025 huggingface dataset:
Bursting Oscillation and Its Mechanism of a Generalized Duffing–Van der Pol System with Periodic Excitation
Authors: Qian Youhua , Zhang Danjin , Lin Bingwen
Published: July 2021

The complex bursting oscillation and bifurcation mechanisms in coupling systems of different scales have been a hot spot domestically and overseas. In this paper, we analyze the bursting oscillation of a generalized Duffing–Van der Pol system with periodic excitation. Regarding this periodic excitation as a slow‐varying parameter, the system can possess two time scales and the equilibrium curves and bifurcation analysis of the fast subsystem with slow‐varying parameters are given. Through numerical simulations, we obtain four kinds of typical bursting oscillations, namely, symmetric fold/fold bursting, symmetric fold/supHopf bursting, symmetric subHopf/fold cycle bursting, and symmetric subHopf/subHopf bursting. It is found that these four kinds of bursting oscillations are symmetric. Combining the transformed phase portrait with bifurcation analysis, we can observe bursting oscillations obviously and further reveal bifurcation mechanisms of these four kinds of bursting oscillations.
A Study of the Brain Network Connectivity in Visual‐Word Pairing Associative Learning and Episodic Memory Reactivating Task
Authors: Zhang Mingxin , Duan Feng , Wang Shan , Zhang Kai , Chen Xuyi , Sun Zhe
Published: July 2021

Episodic memory allows a person to recall and mentally reexperience specific episodes from one’s personal past. Studies of episodic memory are of great significance for the diagnosis and the exploration of the mechanism of memory generation. Most of the current studies focus on certain brain regions and pay less attention to the interrelationship between multiple brain regions. To explore the interrelationship in the brain network, we use an open fMRI dataset to construct the brain functional connectivity and effective connectivity network. We establish a binary directed network of the memory when it is reactivated. The binary directed network shows that the occipital lobe and parietal lobe have the most causal connections. The number of edges starting from the superior parietal lobule is the highest, with 49 edges, and 31 of which are connected to the occipital cortex. This means that the interaction between the superior parietal lobule and the occipital lobe plays the most important role in episodic memory, and the superior parietal lobule plays a more causal role in causality. In addition, memory regions such as the precuneus and fusiform also have some edges. The results show that the posterior parietal cortex plays an important role of hub node in the episodic memory network. From the brain network model, more information can be obtained, which is conducive to exploring the brain’s changing pattern in the whole memory process.
Optimization of Preanalytical Variables for cfDNA Processing and Detection of ctDNA in Archival Plasma Samples
Authors: Nesic Marijana , Bødker Julie S. , Terp Simone K. , Dybkær Karen
Published: July 2021

DNA released from cells into the peripheral blood is known as cell‐free DNA (cfDNA), representing a promising noninvasive source of biomarkers that could be utilized to manage Diffuse Large B‐Cell Lymphoma (DLBCL), among other diseases. The procedure for purification and handling of cfDNA is not yet standardized, and various preanalytical variables may affect the yield and analysis of cfDNA, including the purification kits, blood collection tubes, and centrifugation regime. Therefore, we aimed to investigate the impact of these preanalytical variables on the yield of cfDNA by comparing three different purification kits DNeasy Blood & Tissue Kit (Qiagen), QIAamp Circulating Nucleic Acid Kit (Qiagen), and Quick‐cfDNA Serum & Plasma Kit (Zymo Research). Two blood collection tubes (BCTs), EDTA‐K2 and Cell‐Free DNA (Streck), stored at four different time points before plasma was separated and cfDNA purified, were compared, and for EDTA tubes, two centrifugation regimes at 2000 × g and 3000 × g were tested. Additionally, we have tested the utility of long‐term archival blood samples from DLBCL patients to detect circulating tumor DNA (ctDNA). We observed a higher cfDNA yield using the QIAamp Circulating Nucleic Acid Kit (Qiagen) purification kit, as well as a higher cfDNA yield when blood samples were collected in EDTA BCTs, with a centrifuge regime at 2000 × g. Moreover, ctDNA detection was feasible from archival plasma samples with a median storage time of nine years.
Friend-Invitation Promotion Scheme Used in Electric Carsharing: Empirical Analysis and Policy Implications
Authors: Xie Jiemin , Sun Tuo , Yang Shuangjian
Published: July 2021

The combination of electric vehicle (EV) and carsharing is expected to provide social and environmental benefits, like encouraging sustainable travel behaviors (reducing car ownership and vehicle kilometres of travel) and improving the accessibility and flexibility of urban transport. Thus, electric carsharing is encouraged to be adopted for daily trips, and the operators propose the friend-invitation promotion scheme for the membership expansion. This study explores the effectiveness of this scheme and the characteristics of the scheme participants and their invited friends (e.g., age, friend-invitation pattern, and EV rental pattern). The analysis found that 28.4% of these invited friends would make at least one EV rental after registration, whereas 30.4% of the other members who registered in the same period would do so, indicating that these invited friends were less active. Therefore, suggestions are given based on the EV rental pattern of these invited friends (preferring a longer journey using a smaller but cheaper EV) to enhance the effectiveness of the friend-invitation promotion scheme.
Small Antenna Design of Triple Band for WIFI 6E and WLAN Applications in the Narrow Border Laptop Computer
Authors: Jhang Wei-Chiang , Sun Jwo-Shiun
Published: July 2021

This paper presents the design of a small antenna for use in a wireless local area network (WLAN) and Wi-fi 6E on a narrow-border laptop. The dimensions of the antenna are 43 × 3 × 0.4 mm3, and it features a grounding system simulated by a 200 × 260 mm2 copper plate. At low-frequency bands, a couple-fed right arm can excite the fundamental at 2.45 GHz in the λ/4 resonant mode to cover the range of 2.4–2.848 GHz. At higher bands, the couple-fed left arm and direct-fed right arm can control the higher 3λ/4 mode at 5.825 GHz and 5λ/4 mode at 6.85 GHz. The direct-fed left arm excites the fundamental at 5.16 GHz in the λ/4 resonant mode and, with integration of 5.16, 5.825, and 6.85 GHz, can fully cover the range of 5.15–7.125 GHz. In far-field measurements, the peak gain and efficiency in a WLAN with Wi-Fi 6E were 0.82 and 2.58 dBi and 53% and 68% in the low and high bands, respectively. Overall, the experiments revealed that the antenna exhibits a sufficient level of performance for a narrow-border laptop.
Analytical Solution of Heat Conduction from Turbulence with an Isotropic Example
Authors: Miller Steven A. E.
Published: July 2021

Aerodynamic heating due to turbulence significantly affects the operation of high-speed vehicles and the entrainment of fluid by turbulent plumes. In this paper, the heat generated and convected by fluid turbulence is examined by rearranging the Navier-Stokes equations into a single equation for the fluctuating dependent variables external to unsteady chaotic motions. This equation is similar to the nonhomogeneous heat equation where sources are terms resulting from this rearrangement. Mean and fluctuating quantities are introduced, and under certain circumstances, a heat equation for the fluctuating density results with corresponding mean and fluctuating source terms. The resultant equation is similar to Lighthill’s acoustic analogy and is a “heat analogy.” A solution is obtained with the use of Green’s function as long as the observer is located outside the region of chaotic motion. Predictions for the power spectrum are shown for high Reynolds number isotropic turbulence. The power spectrum decays as the inverse of the wavenumber of the turbulent velocity fluctuations. The developed theory can easily be applied to other turbulent flows if the statistics of unsteady motion can be estimated.
Association between Uric Acid and In-Hospital Heart Failure in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Liu Cun-Fei , Song Kai-You , Zhou Wei-Ning , Wei Yan-Jin
Published: July 2021

Objective. To investigate the association of serum uric acid levels with in-hospital heart failure (HF) in patients with acute myocardial infarction (AMI) who are undergoing percutaneous coronary intervention (PCI). Methods. Two hundred sixteen patients with AMI who were treated with PCI were enrolled in our study. Univariate and multivariate logistic regression analyses were performed to estimate the associations between uric acid levels and the risk of in-hospital HF in AMI patients. Analyses of the areas under the receiver operating characteristic (ROC) curve were performed to determine the accuracy of uric acid levels in predicting in-hospital HF. Results. A dose-response relationship was found for the incidence of in-hospital HF and levels of uric acid, showing increased HF from the lowest to the highest tertile of uric acid. Compared with subjects in the bottom tertile, the adjusted odds ratio for in-hospital HF was 1.92 (95% CI 0.70–5.24) and 3.33 (95% CI 1.18-9.46) in the second tertile group and the third tertile group, respectively. Every 1 mg/dl increase in the serum uric acid level was associated with a 1.60-fold increased risk of incident in-hospital HF (OR, 1.60; 95% CI 1.22–2.11;

P
=
0.001

). ROC curve analysis showed that the optimal cut-off value of uric acid to predict in-hospital HF was 5.75 mg/dl with a sensitivity of 69.2% and specificity of 56.3%. Conclusions. Our study showed that the serum uric acid level on admission is an independent predictor of in-hospital heart failure in patients with AMI.
Adoption of Coffee Shade Agroforestry Technology and Shade Tree Management in Gobu Seyo District, East Wollega, Oromia
Authors: Urgessa Waktola Tolera , Fekadu Kidist
Published: July 2021

Coffee production in the form of agroforestry practices is the most important management approach to improve the livelihoods of the farming community. This study was conducted to assess factors affecting the adoption of the technology, its socioeconomic and environmental benefits, and the management practices related to the technology. Out of eight kebeles in the district, two kebeles were selected purposively based on the existing and extensive agroforestry practices. Four villages were selected randomly. Based on the preidentified criteria as coffee growers and nongrowers, coffee growers were selected purposively. Then a total of 120 households were selected by Simple Random Sampling Method. Data were collected by using structured interview and field observation. The data were analyzed by using descriptive statistics analysis. The logit model was used to identify the factors affecting the adoption of coffee shade agroforestry technology. The results of this study showed that adoption of coffee shade agroforestry technology had a positive relationship and was statistically significant at 1% level with age and area covered by coffee production, while household composition and training were at 5% level. Education level, land holding, and extension services also had positive relationship, but it was not statistically significant. The farmers in the study area mentioned other benefits of these technologies such as for animal feed, firewood and construction materials, medicinal purpose, erosion control, honey bee production, and soil fertility enhancement. Different management activities were also identified in the area (such as composting, pruning, watering, and weeding). Coffee shade agroforestry technology was important to diversify the agricultural products, to solve the problem of livelihood, and adds economic and environmental benefits.
PICK1 Deficiency Exacerbates Sepsis‐Associated Acute Kidney Injury
Authors: Dou Qian , Tong Hang , Yang Yichun , Zhang Han , Gan Hua
Published: July 2021

We performed in vitro and in vivo experiments to explore the role of protein kinase C‐binding protein 1 (PICK1), an intracellular transporter involved in oxidative stress‐related neuronal diseases, in sepsis‐related acute kidney injury (AKI). Firstly, PCR, western blotting, and immunohistochemistry were used to observe the expression of PICK1 after lipopolysaccharide‐ (LPS‐) induced AKI. Secondly, by inhibiting PICK1 in vivo and silencing PICK1 in vitro, we further explored the effect of PICK1 on AKI. Finally, the relationship between PICK1 and oxidative stress and the related mechanisms were explored. We found that the expression of PICK1 was increased in LPS‐induced AKI models both in vitro and in vivo. PICK1 silencing significantly aggravated LPS‐induced apoptosis, accompanied by ROS production in renal tubular epithelial cells. FSC231, a PICK1‐specific inhibitor, aggravated LPS‐induced kidney injury. Besides, NAC (N‐acetylcysteine), a potent ROS scavenger, significantly inhibited the PICK1‐silencing‐induced apoptosis. In conclusion, PICK1 might protect renal tubular epithelial cells from LPS‐induced apoptosis by reducing excessive ROS, making PICK1 a promising preventive target in LPS‐induced AKI.
Quantitative Magnetic Resonance Imaging Analysis of Early Markers of Upper Cervical Cord Atrophy in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
Authors: Adibi Iman , Najafi Afshin , Merajifar Fouad , Ramezani Neda , Nouri Hosein , Jalilvand Nassim , Ashtari Fereshteh , Vard Alireza , Shaygannejad Vahid
Published: July 2021

Purpose. To quantitatively analyze the C2/C3 segments of the spinal cord on magnetic resonance imaging (MRI) scans of neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) patients in their first five years of the disease and to investigate the intergroup differences regarding markers of spinal cord atrophy and their correlations with expanded disability status scale (EDSS). Materials and Methods. Twenty NMOSD patients and twenty RRMS patients, within their first five years of the disease, were enrolled in this cross-sectional study. All patients underwent spinal cord MR imaging using 1.5 Tesla systems, and C2/C3 portions of the spinal cord were segmented in the obtained scans. C2/C3 anteroposterior diameter (C2/C3 SC-APD), transversal diameter (C2/C3 SC-TD), and cross-sectional area (C2/C3 SC-CSA) were quantitatively measured using Spinal Cord Toolbox v.4.3. Results. Three NMOSD patients were seropositive for anti-AQP4 IgG. The mean C2/C3 SC-CSA in NMOSD patients was significantly lower than in RRMS patients. NMOSD patients had significantly lower C2/C3 SC-TDs than RRMS patients. With the three anti-AQP4+ patients excluded from the analysis, C2/C3 SC-TD was negatively correlated with EDSS. Conclusion. In the early stages of the disease, quantitative evaluation of C2/C3 spinal cord parameters, including cross-sectional area and transversal diameter in NMOSD patients, appears to be of potential diagnostic and prognostic value.
Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Bull Caroline J. , Mesaros Clementina , Finan Jennifer M. , Carens Madeleine , Ho Elaine S. , Xu Jimmy P. , Godfrey Jason , Brennan Paul , Johansson Mattias , Purdue Mark P. , Chanock Stephen J. , Mariosa Daniela , Timpson Nicholas J. , Vincent Emma E. , Keith Brian , Blair Ian A. , Skuli Nicolas , Simon M. Celeste
Published: July 2021

Clear cell renal cell carcinoma (ccRCC) is characterized by large intracellular lipid droplets containing free and esterified cholesterol; however, the functional significance of cholesterol accumulation in ccRCC cells is unknown. We demonstrate that, surprisingly, genes encoding cholesterol biosynthetic enzymes are repressed in ccRCC, suggesting a dependency on exogenous cholesterol. Mendelian randomization analyses based on 31,000 individuals indicate a causal link between elevated circulating high-density lipoprotein (HDL) cholesterol and ccRCC risk. Depriving ccRCC cells of either cholesterol or HDL compromises proliferation and survival in vitro and tumor growth in vivo; in contrast, elevated dietary cholesterol promotes tumor growth. Scavenger Receptor B1 (SCARB1) is uniquely required for cholesterol import, and inhibiting SCARB1 is sufficient to cause ccRCC cell-cycle arrest, apoptosis, elevated intracellular reactive oxygen species levels, and decreased PI3K/AKT signaling. Collectively, we reveal a cholesterol dependency in ccRCC and implicate SCARB1 as a novel therapeutic target for treating kidney cancer.

Significance:

We demonstrate that ccRCC cells are auxotrophic for exogenous cholesterol to maintain PI3K/AKT signaling pathway and ROS homeostasis. Blocking cholesterol import through the HDL transporter SCARB1 compromises ccRCC cell survival and tumor growth, suggesting a novel pharmacologic target for this disease.

This article is highlighted in the In This Issue feature, p. 2945
Rationally Designed Transgene-Encoded Cell-Surface Polypeptide Tag for Multiplexed Programming of CAR T-cell Synthetic Outputs
Authors: Johnson Adam J. , Wei Jia , Rosser James M. , Künkele Annette , Chang Cindy A. , Reid Aquene N. , Jensen Michael C.
Published: July 2021

Synthetic immunology, as exemplified by chimeric antigen receptor (CAR) T-cell immunotherapy, has transformed the treatment of relapsed/refractory B cell–lineage malignancies. However, there are substantial barriers—including limited tumor homing, lack of retention of function within a suppressive tumor microenvironment, and antigen heterogeneity/escape—to using this technology to effectively treat solid tumors. A multiplexed engineering approach is needed to equip effector T cells with synthetic countermeasures to overcome these barriers. This, in turn, necessitates combinatorial use of lentiviruses because of the limited payload size of current lentiviral vectors. Accordingly, there is a need for cell-surface human molecular constructs that mark multi-vector cotransduced T cells, to enable their purification ex vivo and their tracking in vivo. To this end, we engineered a cell surface–localizing polypeptide tag based on human HER2, designated HER2t, that was truncated in its extracellular and intracellular domains to eliminate ligand binding and signaling, respectively, and retained the membrane-proximal binding epitope of the HER2-specific mAb trastuzumab. We linked HER2t to CAR coexpression in lentivirally transduced T cells and showed that co-transduction with a second lentivirus expressing our previously described EGFRt tag linked to a second CAR efficiently generated bispecific dual-CAR T cells. Using the same approach, we generated T cells expressing a CAR and a second module, a chimeric cytokine receptor. The HER2txEGFRt multiplexing strategy is now being deployed for the manufacture of CD19xCD22 bispecific CAR T-cell products for the treatment of acute lymphoblastic leukemia (NCT03330691).
TIGIT-Fc Promotes Antitumor Immunity
Authors: Shen Xian , Fu Wenyan , Wei Yongpeng , Zhu Junle , Yu Yue , Lei Changhai , Zhao Jian , Hu Shi
Published: July 2021

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a checkpoint receptor that mediates both T-cell and natural killer (NK)–cell exhaustion in tumors. An Fc-TIGIT fusion protein was shown to induce an immune-tolerance effect in a previous report, but the relevance of the TIGIT-Fc protein to tumor immunity is unknown. Here, we found that TIGIT-Fc promotes, rather than suppresses, tumor immunity. TIGIT-Fc treatment promoted the effector function of CD8+ T and NK cells in several tumor-bearing mouse models. TIGIT-Fc treatment resulted in potent T cell– and NK cell–mediated tumor reactivity, sustained memory-induced immunity in tumor rechallenge models, enhanced therapeutic effects via an antibody against PD-L1, and induction of Th1 development in CD4+ T cells. TIGIT-Fc showed a potent antibody-dependent cell-mediated cytotoxicity effect but had no intrinsic effect on tumor cell development. Our findings elucidate the role of TIGIT-Fc in tumor immune reprogramming, suggesting that TIGIT-Fc treatment alone or in combination with other checkpoint receptor blockers is a promising anticancer therapeutic strategy.
Unexpected Etiology in a Case of Bilateral Maculopathy
Authors: Patel Prem , Jones Kaylie , Friedman Deborah I. , Birch David G. , Ufret-Vincenty Rafael L.
Published: July 2021

A 74-year-old woman with a history of rheumatoid arthritis using hydroxychloroquine presented with gradually progressive decreased vision in both eyes and was found to have a bilateral maculopathy. Initial genetic testing was negative, and after discussing the low likelihood of her severe findings being secondary to her relatively low hydroxychloroquine exposure, the possibility of an autoimmune retinopathy was entertained. Updated data on the genetic testing reclassified one of her mutations in HGSNAT as pathogenic. This case highlights the value of genetic testing and the need to keep a high index of suspicion even after initial negative results, given the fact that our knowledge of mutations leading to retinal degeneration is constantly evolving.
Rhabdomyolysis, Acute Kidney Injury, and a Novel Frameshift Mutation in a Child with Glutaric Acidemia Type I
Authors: Huang Linlin , Shi Ting , Li Ying , Li Xiaozhong
Published: July 2021

This is a case report of a girl with glutaric acidemia type I (GA-I) who experienced rhabdomyolysis and acute kidney injury (AKI). Her first acute metabolic crisis occurred at the age of 5 months, which mainly manifested as irritable crying, poor appetite, and hyperlactatemia. Mutation analysis showed 2 pathogenic mutations in the glutaryl-CoA dehydrogenase (GCDH) gene, which were c.383G>A (p.R128Q) and c.873delC (p.N291Kfs*41), the latter of which is a novel frameshift mutation of GA-I. She had a febrile illness at the age of 12 months, followed by AKI and severe rhabdomyolysis. Four days of continuous venovenous hemodiafiltration (CVVHDF) helped to overcome this acute decompensation. This case report describes a novel mutation in the GCDH gene, that is, c.873delC (p.N291Kfs*41). Also, it highlights the fact that patients with GA-I have a high risk of rhabdomyolysis and AKI, which may be induced by febrile diseases and hyperosmotic dehydration; CVVHDF can help to overcome this acute decompensation.
Extrusion of both Superficial and Deep Cuffs of a Functional Double-Cuff Peritoneal Dialysis Catheter after Significant Weight Loss
Authors: Ganapathy Aravindh S. , Powell Myron S. , Pirkle James L.
Published: July 2021

Extrusion of the superficial cuff of a peritoneal dialysis (PD) catheter is an uncommon complication that may be associated with infection or malfunction. However, extrusion of both the superficial and deep cuffs of a double-cuff catheter is rare and uniformly associated with failure and peritonitis. We report a case of a presternal-type PD double-cuff catheter with extrusion of both cuffs through an abdominal exit site after 6 years of use that has remained functional, which has not been previously reported. In this case, the patient had achieved a 60-kg weight loss resulting in retraction of the subcutaneous tissue around both cuffs, while the catheter was held in place by the titanium connector between the presternal extension tubing and the inner, coiled catheter. In such special circumstances, extrusion of both cuffs may not necessitate urgent catheter removal. A review of the literature revealed previous cases of superficial cuff extrusions with catheters remaining functional but not with deep cuff extrusion.
Removal of Common Warts by High-Intensity Focused Ultrasound: An Introductory Observation
Authors: Bove Torsten , Zawada Tomasz , Jessen Alexander , Poli Mattia , Serup Jørgen
Published: July 2021

Therapies of common warts are cumbersome and not very effective. Recurrences are common. A new 20 MHz high-intensity focused ultrasound (HIFU) method is introduced as a new potential treatment modality. With HIFU, selected targets in the epidermis and dermis can be treated with full control of the depth and position of the ultrasound lesion and the energy applied to the target. The treatment can be monitored directly in real-time via an integrated dermoscope in the ultrasound probe. Two warts were treated with 8–10 shoulder-by-shoulder treatment doses, focal depth 1.3 mm, and 1.2 J/dose. Pretreatment ultrasound B-mode scanning had shown the thickness and depth of the warts. The treated areas developed a dry wound covered by a crust over the next 1–2 days. After 2 weeks the skin was healed, with no wart and no scar. Observation showed no reoccurrence. HIFU has future potential for treatment of common warts and flat warts, and a broad range of skin lesions being logic further candidates for targeted ablative treatment. One single treatment may suffice. It is, therefore, a new modality in dermatology with a large range of indications.
Recurrence of Adult Granulosa Cell Tumor in the Greater Omentum 11 Years after Surgery
Authors: Ohta Mineto , Hara Yasuyuki , Kashiwadate Toshiaki , Chin Masahiro , Hagiwara Motohisa , Nakanishi Wataru , Ito Ken , Nishida Akiko , Hashizume Eiji
Published: July 2021

Adult-type ovarian granulosa cell tumors (AGCTs) are very rare tumors that account for <5% of all ovarian carcinomas. AGCTs have low malignancy potential and rarely metastasize 5–30 years after the initial diagnosis. Because time has passed from the first surgery and because recurrence develops in various locations, the differential diagnosis is difficult. In particular, tumors developing in the greater omentum are encountered rarely, and it is necessary to carefully consider the differential diagnosis, including primary and secondary neoplasms. Although CT is useful to detect omental tumors, the diagnosis requires invasive procedures. We report a case of AGCT recurrence in the greater omentum that was resected during laparoscopic cholecystectomy. A patient visited our hospital with right-sided abdominal pain. The CT revealed gallbladder stones, a ureteral stone, and a right abdominal mass. The diagnosis of the abdominal tumor was difficult on the basis of blood biochemical testing, gastrointestinal endoscopy, or image inspection. Although the patient underwent several previous surgeries and there were no findings of malignancy with positron emission tomography, we chose to resect the tumor for combined diagnosis and treatment during laparoscopic cholecystectomy. Intraoperative findings showed that the tumor originated from the greater omentum, and the tumor was diagnosed as AGCT recurrence by pathology. A recurrence of AGCT in the greater omentum is very rare, and laparoscopic surgery was safe and useful for resection, in our case.
Tineа Corporis with Trichophyton Rubrum Mimicking a Flare-Up of Psoriasis UnderTreatment with IL17-Inhibitor Ixekizumab
Authors: Emelianov Vladimir , Feldmeyer Laurence , Yawalkar Nikhil , Heidemeyer Kristine
Published: July 2021

Biologics, as IL17 inhibitors, are frequently prescribed for moderate to severe plaque psoriasis. Although mucocutaneous candida infections are a well-known side effect of IL-17 inhibitors, there is no data about dermatophyte infection under this therapy. Generalized tinea corporis can mimic the clinical picture of psoriasis, especially if concomitant treatment with topical corticosteroids is used. Therefore, physician should be aware of this differential diagnosis if they suspect a loss of efficacy of IL-17-inhibitors with a flare-up of psoriasis.
Secondary Hemophagocytic Lymphohistiocytosis Complicated by a Cavitary Lung Lesion in a Kidney Transplant Recipient
Authors: Muras-Szwedziak Katarzyna , Tylski Maciej , Masajtis-Zagajewska Anna , Nowicki Michał
Published: July 2021

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening condition caused by an uncontrolled immunological response. It can develop secondary to malignancies, infections, systemic diseases, and immunosuppression. Multiple risk factors may present in kidney transplant recipients; however, the cases of HLH in this population have been described sparsely. We report a case of a 39-year-old female kidney transplant recipient who presented to the hospital nearly 3.5 years after the transplantation with general malaise, recent history of weight loss, fevers, and persistent anemia. Laboratory tests showed pancytopenia, hyperferritinemia, hypertriglyceridemia, and increased activity of lactate dehydrogenase. A bone marrow aspiration revealed hemophagocytosis, which led to the diagnosis of HLH. Therapy consisting of high-dose steroids and plasma exchanges was administered, resulting in a significant improvement of blood count parameters and the patient’s general condition. While searching for the triggering disease, a single cavitary lesion in the right lung was revealed in a chest radiograph. Computed tomography scan, bronchoscopy, and additional laboratory testing did not reveal a definitive cause of the lesion. We suspect that the lesion may be a consequence of HLH. The patient was disqualified from thoracic surgery due to multiple comorbidities. Even though HLH is a rare condition, it should be taken into consideration in a kidney transplant patient presenting with unspecific symptoms accompanied by a bicytopenia. It has an unpredictable course that often results in serious complications. Thus close follow-up of the patient and a wide array of imaging and laboratory tests remain crucial.
Enteral Feeding Strategies in Preterm Neonates ≤32 weeks Gestational Age: A Systematic Review and Network Meta-Analysis
Authors: Ramaswamy Viraraghavan Vadakkencherry , Bandyopadhyay Tapas , Ahmed Javed , Bandiya Prathik , Zivanovic Sanja , Roehr Charles Christoph
Published: July 2021

Introduction: Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered. Methods: Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); advancement day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); increment volume: small volume (SV) (<20 mL/kg/day), moderate volume (MoV) (20–< 30 mL/kg/day), and large volume (≥30 mL/kg/day); and full enteral feeding from the first day. Sixteen regimens were evaluated. Combined outcome of necrotizing enterocolitis (NEC) stage ≥ II or mortality before discharge was the primary outcome. Results: A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE–very low). Conclusions: Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted.
Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants
Authors: Brown Carolyn A. , Lally Cathy , Kupelian Varant , Flanders W. Dana
Published: July 2021

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder characterized by progressive deterioration of motor neurons. Assessment of the size/geographic distribution of the ALS population, including ALS with genetic origin, is needed to understand the burden of the disease and the need for clinical intervention and therapy. Objectives: The main objective of this study was to estimate the number of prevalent and incident ALS cases overall and superoxide dismutase 1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) ALS in 22 countries across Europe (Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, and UK), North America (USA and Canada), Latin America (Argentina, Brazil, Colombia, Mexico, and Uruguay), and Asia (China, Japan, South Korea, and Taiwan). Methods: A comprehensive literature search was conducted to identify population-based studies reporting ALS prevalence and/or incidence rates. Pooled prevalence and incidence rates were obtained using a meta-analysis approach at the country and regional geographic level. A country-level pooled estimate was used when ≥2 studies were available per country and geographic regional pooled estimates were used otherwise. The proportion of cases with a SOD1 or C9orf72 mutation among sporadic (sALS) and familial (fALS) cases were obtained from a previous systematic review and meta-analysis. Results: Pooled prevalence rates (per 100,000 persons) and incidence rates (per 100,000 person-years) were 6.22 and 2.31 for Europe, 5.20 and 2.35 for North America, 3.41 and 1.25 for Latin America, 3.01 and 0.93 for Asian countries excluding Japan, and 7.96 and 1.76 for Japan, respectively. Significant heterogeneity in reported incidence and prevalence was observed within and between countries/geographic regions. The estimated number of 2020 ALS cases across the 22 countries is 121,028 prevalent and 41,128 incident cases. The total estimated number of prevalent SOD1 cases is 2,876 cases, of which, 1,342 (47%) were fALS and 1,534 (53%) were sALS, and the number of incident SOD1 cases is 946 (434 [46%] fALS and 512 [54%] sALS). The total estimated number of prevalent C9orf72 cases is 4,545 (1,198 [26%] fALS, 3,347 [74%] sALS), and the number of incident C9orf72 cases is 1,706 (450 [26%] fALS and 1,256 [74%] sALS). Discussion: The estimated number of patients with SOD1 and C9orf72 ALS suggests that although the proportions of SOD1 and C9orf72 are higher among those with fALS, the majority of SOD1 and C9orf72 ALS cases may be found among those with sALS (about 53 and 74%, respectively). These results suggest that classification of fALS based on reported family history does not capture the full picture of ALS of genetic origin.
Involvement of the Auditory Pathway in Spinocerebellar Ataxia Type 7
Authors: Ramos-Languren Laura E. , Rodríguez-Labrada Roberto , Magaña Jonathan J. , Canales-Ochoa Nalia , González-Zaldivar Yanetza , Velázquez-Pérez Luis , González-Piña Rigoberto
Published: July 2021

Background: Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a mutation in the ATXN7 gene. The involvement of the brainstem auditory pathway in pathogenesis of this disease has not been systematically assessed. Aim: To determine involvement of the brainstem auditory pathway in SCA7 patients and its relationship to clinical features of the disease. Methods: In this case-control study, brainstem auditory-evoked potentials (BAEPs) were assessed in 12 SCA7 patients with clinical and molecular diagnosis, compared to 2 control groups of 16 SCA2 patients and 16 healthy controls. Results: SCA7 patients exhibited significant prolongation of I-wave and III-wave latencies, whereas SCA2 patients showed increased latencies for III and V waves and I–III interpeak interval. SCA7 patients with larger I-wave latencies exhibited larger CAG repeats, earlier onset age, and higher SARA scores, but in SCA2 cases, these were not observed. Conclusions: BAEP tests revealed functional involvement of the auditory pathway in SCA7 (mainly at) peripheral portions, which gave new insights into the disease physiopathology different from SCA2 and may unravel distinct pathoanatomical effects of polyQ expansions in the central nervous system. Significance: These findings offer important insights into the distinctive disease mechanisms in SCA7 and SCA2, which could be useful for differential diagnosis and designing specific precision medicine approaches for both conditions.
Case Report: De Quervain’s Thyroiditis as a Long-Term Sequelae Complication to SARS-CoV-2 Infection
Authors: Kong Mark , La Porte Sarah
Published: July 2021

A 44-year-old man presented with an enlarged painful lower anterior neck lump with elevated serum concentrations of free thyroxine (T4) and tri-iodothyronine (T3), alongside the presence of antithyroid peroxidase antibodies. Prior to presentation, the patient was demonstrating recovery from a SARS-CoV-2 infection that required sedation, intubation, and invasive ventilation in the intensive care unit (ICU) for 11 days. Ultrasound examination of the thyroid demonstrated features of De Quervain’s (subacute) thyroiditis. This corresponded to the clinical picture, and continuous thyroid function tests were arranged. Emerging evidence throughout the SARS-CoV-2 pandemic describes the long-term sequelae of the infection, including developing atypical effects on the thyroid gland. This case report emphasises the association of painful subacute thyroiditis with post-viral infection and its manifestation during recovery from severe SARS-CoV-2, suggesting that follow-up thyroid function testing should be considered in patients discharged from the ICU who develop neck discomfort.
Molecular Mechanisms Associated with Antidepressant Treatment on Major Depression
Authors: Ramos-da-Silva Lívia , Carlson Pamela T. , Silva-Costa Licia C. , Martins-de-Souza Daniel , de Almeida Valéria
Published: July 2021

Major depressive disorder (MDD) is a complex and multifactorial psychiatric disorder that causes serious health, social, and economic concerns worldwide. The main treatment of the symptoms is through antidepressant (AD) drugs. However, not all patients respond properly to these drugs. Omic sciences are widely used to analyze not only biomarkers for the AD response but also their molecular mechanism. In this review, we aimed to focus on omics data to better understand the molecular mechanisms involving AD effects on MDD. We consistently found, from preclinical to clinical data, that glutamatergic transmission, immune/inflammatory processes, energy metabolism, oxidative stress, and lipid metabolism were associated with traditional and potential new ADs. Despite efforts of studies investigating biomarkers of response to ADs, which could contribute to personalized treatment, there is no biomarker panel available for clinical application. From clinical genomic studies, we found that the main findings contribute to the development of pharmacogenomic tests for AD efficacy for each patient. Several studies pointed at DRD2, PXDNL, CACNA1E, and CACNA2D1 genes as potential targets for MDD treatment and the efficacy and rapid-antidepressant effect of ketamine. Finally, more in-depth studies of the molecular targets pointed here are needed to determine the clinical relevance and provide further evidence for precision MDD treatment.
Auditory-Perceptual Evaluation of Vocal Characteristics in Patients with the New Coronavirus Disease 2019
Authors: Saki Nader , Zamani Peyman , Bayat Arash , Nikakhlagh Soheila , Moghateli Nahid , Salmanzadeh Shokrollah
Published: July 2021

Introduction: Due to the upper and lower respiratory involvement in coronavirus disease 2019 (COVID-19), the voice quality of these patients is expected to be impaired. In this study, we aimed to conduct an auditory-perceptual evaluation of the vocal characteristics of patients with different severities of COVID-19. Methods: One hundred two patients with mild, moderate, or severe COVID-19 as well as 30 healthy individuals were recruited to compare their respiratory/phonatory parameters. The Persian version of the CAPE-V and GRBAS scales, along with the maximum phonation time and s/z ratio values were used to evaluate the severity of respiratory/phonatory disorders during verbal tasks in the participants. Results: Significant differences were found between the subgroups of patients and their healthy counterparts in all respiratory/phonatory parameters (p ≤ 0.03) except the s/z ratio (p = 0.81). Conclusions: Based on auditory-perceptual assessments, patients with COVID-19 showed dysphonia. The severity of dysphonia was significantly different among patients with different severities of COVID-19. Smoking can also play a significant role in vocal dysfunction in COVID-19 patients.
Loss of Hepatic Angiotensinogen Attenuates Sepsis-Induced Myocardial Dysfunction
Authors: Rong Jiabing , Tao Xinran , Lin Yao , Zheng Haiqiong , Ning Le , Lu Hong S. , Daugherty Alan , Shi Peng , Mullick Adam E. , Chen Sicong , Zhang Zhaocai , Xu Yinchuan , Wang Jian’an
Published: July 2021

Rationale:

The renin-angiotensin system is a complex regulatory network that maintains normal physiological functions. The role of the renin-angiotensin system in sepsis-induced myocardial dysfunction (SIMD) is poorly defined. AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system and gives rise to all angiotensin peptides. The effects and mechanisms of AGT in the development of SIMD have not been defined.

Objective:

To determine a role of AGT in SIMD and investigate the underlying mechanisms.

Methods and Results:

Either intraperitoneal injection of lipopolysaccharide or cecal ligation and puncture significantly enhanced AGT abundances in liver, heart, and plasma. Deficiency of hepatocyte-derived AGT, rather than cardiomyocyte-derived AGT, alleviated septic cardiac dysfunction in mice and prolonged survival time. Further investigations revealed that the effects of hepatocyte-derived AGT on SIMD were partially associated with augmented Ang II (angiotensin II) production in circulation. In addition, hepatocyte-derived AGT was internalized by LRP1 (LDL [low-density lipoprotein] receptor-related protein 1) in cardiac fibroblasts and subsequently activated NLRP3 (NLR family pyrin domain-containing 3) inflammasome via an Ang II–independent pathway, ultimately promoting SIMD by suppressing SERCA2a (sarco[endo]plasmic reticulum Ca[2+]-ATPase 2a) abundances in cardiomyocytes.

Conclusions:

Hepatocyte-derived AGT promoted SIMD via both Ang II–dependent and Ang II–independent pathways. We identified a liver-heart axis by which AGT regulated development of SIMD. Our study may provide a potential novel therapeutic target for SIMD.
Treatment Inertia in Patients With Familial Hypercholesterolemia
Authors: Langer Anatoly , Mancini G. B. John , Tan Mary , Goodman Shaun G. , Ahooja Vineeta , Grégoire Jean , Lin Peter J. , Stone James A. , Leiter Lawrence A.
Published: July 2021

Background

We studied care gap in patients with familial hypercholesterolemia (FH) with respect to lipid‐lowering therapy.

Methods and Results

We enrolled patients with cardiovascular disease (CVD) or FH and low‐density lipoprotein‐cholesterol >2.0 mmol/L despite maximally tolerated statin therapy. During follow‐up physicians received online reminders of treatment recommendations of 2009 patients (median age, 63 years, 42% women), 52.4% had CVD only, 31.7% FH only, and 15.9% both CVD and FH. Patients with FH were younger and more likely to be women and non‐White with significantly higher baseline low‐density lipoprotein‐cholesterol level (mmol/L) as compared with patients with CVD (FH 3.92±1.48 versus CVD 2.96±0.94,
P
<0.0001). Patients with FH received less statin (70.6% versus 79.2%,
P
=0.0001) at baseline but not ezetimibe (28.1% versus 20.4%,
P
=0.0003). Among patients with FH only, 45.3% were at low‐density lipoprotein target (≥ 50% reduction from pre‐treatment level or low‐density lipoprotein <2.5 mmol/L) at baseline and increasing to 65.8% and 73.6% by visit 2 and 3, respectively. Among patients with CVD only, none were at recommended level (≤2.0 mmol/L) at baseline and 44.3% and 53.3% were at recommended level on second and third visit, respectively. When primary end point was analyzed as a difference between baseline and last available follow‐up observation, only 22.0% of patients with FH only achieved it as compared with 45.8% with CVD only (
P
<0.0001) and 55.2% with both FH+CVD (
P
<0.0001).

Conclusions

There is significant treatment inertia in patients with FH including those with CVD. Education focused on patients with FH should continue to be undertaken.
“None of the Art Stuff Makes Sense Anymore”: An Interview with Luis Camnitzer
Authors: Weiss Rachel
Published: July 2021

Weiss and Camnitzer discuss his ideas about the transformative potential of art in education; his experiences in and thoughts about Cuba and Cuban art; his “Uruguayan Torture” series of prints, and his thoughts about productive anarchy.
Amy Sara Carroll's ReMex: Toward an Art History of the NAFTA Era
Authors: Emmelhainz Irmgard
Published: July 2021

Amy Sara Carroll's ReMex: Toward an Art History of the NAFTA Era interprets Mexico City-based, feminist, and border, or Chicano, art in and around the 1990s. Its premise is that aesthetics and politics “form a loop” in order to express what the author calls “Greater Mexico.” With this term, Carroll proposes that “Mexico” is no longer a territory but rather an imaginary that transcends its geographic borders. In her view, the denationalization brought about by the liberalization of markets led to a multicultural utopia best expressed in border art and art concerned with race and gender issues. In her account, aesthetic practice must serve as a direct weapon against “NAFTAfication” and colonial heteropatriarchy. Carroll draws an analogy between the selling out of the nation through the NAFTA treaty and the selling out of “post-Mexican” art to the global culture industry through the ambition of curators, cultural managers and artists who placed Mexico and Mexican contemporary art as key global art destinations by taking advantage of generous State sponsorship brought about by market liberalization. Any hint of cosmopolitism is suspicious and thus Carroll insists on “ReMexing” Mexico.
The Reassertion of National Sovereignty
Authors: Hirschmann Gisela
Published: July 2021

International organizations (io s) have repeatedly been challenged in their existence. In this essay, I review arguments about the causes of their decline and survival in existing research. While the majority of research has focused on structural pressures such as geopolitical crises, I argue that io s can also be threatened by member-states reasserting their sovereignty, for example through budget cuts, non-compliance with core norms, obstruction of staff appointments and membership withdrawal. More systematic research is required to investigate when these challenges are more likely to lead to the demise of io s and which factors make io s survive these challenges.
Five new species of Limacodidae (Lepidoptera: Zygaenoidea) from South-East Asia
Authors: SOLOVYEV ALEXEY V. , SALDAITIS AIDAS
Published: July 2021

The species Iragoides dudai sp. nov. from China (Sichuan), Euphlyctina butvilai sp. nov. from China (Zhejiang and Yunnan), Sansarea alenae sp. nov. from China (Yunnan), Narosoideus witti sp. nov. from China (Sichuan, Yunnan, Shaanxi, and Jiangxi), Griseothosea mousta sp. nov. from China (Yunnan), Thailand (Chiang Mai, Nan and Chiang Dao), and Laos (Luang Namtha and Luang Prabang) are described as new to science. The taxonomical status of dark and pale forms of Iragoides crispa (Swinhoe, 1890) is discussed.
Is Knipowitschia cameliae Nalbant et Oţel, 1995 (Osteichthyes: Gobiiformes: Gobiidae) a valid species?
Authors: IFTIME ALEXANDRU , OŢEL VASILE
Published: July 2021

N/A